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  • CLASSES

    Emergency Contraceptives and Abortifacients
    Glucocorticoid Receptor Antagonists

    BOXED WARNING

    Bleeding, fever, infection, sepsis

    Mifepristone, when used for medical abortion (e.g., Mifeprex), has been associated with cases of serious bacterial infection, including, although rare, fatal sepsis and septic shock. Patients should promptly report heavy vaginal bleeding, fever, or abdominal pain following treatment. A sustained fever 100.4 degrees F or above for more than 4 hours, severe abdominal pain, pelvic tenderness, syncope, or prolonged heavy vaginal bleeding, more than 24 hours after a medical abortion may be an indication of infection and warrant intervention; however, practitioners should also be alert to atypical presentations including leukocytosis, tachycardia, hemoconcentration, and general malaise (including weakness, nausea, vomiting, or diarrhea). Ensure the patient knows who to call and what to do if she experiences any of these symptoms. Uterine bleeding is expected during medical abortion; however, prolonged heavy bleeding (soaking through 2 thick full-size sanitary pads per hour for 2 consecutive hours) may be a sign of incomplete medical abortion or other complications. Heavy vaginal bleeding after a medical abortion should prompt the patient to seek immediate medical attention. Serious bacterial infections and sepsis, including fatalities, have occurred following the use of mifepristone and vaginal misoprostol and have been reported in the U.S. Clostridium sordellii has been identified as the causative organism in some cases; none of these patients presented with a fever, but they did present with sinus tachycardia, low blood pressure, leukocytosis, and very high red blood cell counts. The patients also had other atypical symptoms including weakness, nausea/vomiting, or diarrhea with or without abdominal pain. No causal relationship has been established between these events and the mifepristone-misoprostol regimen for termination of pregnancy. Patients with endogenous Cushing's syndrome are at risk for opportunistic infection such as Pneumocystis jiroveci pneumonia (PCP) during mifepristone treatment. Patients may present with respiratory distress shortly after initiation of the drug. Appropriate diagnostic tests should be undertaken and treatment for Pneumocystis jiroveci should be considered.

    Contraception requirements, pregnancy, pregnancy testing, reproductive risk

    Mifepristone has potent antiprogestational effects that will result in the termination of pregnancy. Mifepristone for treatment of Cushing's syndrome (e.g., Korlym) is contraindicated in women who are pregnant. Exclude pregnancy before the initiation of treatment and advise the female patient of the reproductive risk. Pregnancy testing should occur, and female patients of childbearing potential should have a negative pregnancy test before starting the chronic use of mifepristone and such women also must have a repeat negative pregnancy test if the drug is discontinued for more than 14 days. There are contraception requirements for female patients of reproductive potential during chronic treatment with mifepristone; all female patients of childbearing potential should use non-hormonal contraceptives during treatment and for 1 month after stopping treatment, unless the patient has had a surgical sterilization, in which case no additional contraception is needed. Should a woman become pregnant while taking mifepristone chronically, the woman should be apprised of the potential fetal risk. There are no data that assess the risk of birth defects in women exposed to mifepristone during pregnancy. Available data limited to exposure following a single dose of mifepristone during pregnancy showed a higher rate of major birth defects compared to the general population comparator. Animal studies also indicate a potential for fetal harm. Medical abortion with mifepristone (e.g., Mifeprex) is indicated when the objective is termination of the pregnancy at 70 days gestation or less, but should not be used for termination of later pregnancy. Mifepristone disrupts pregnancy, leading to the expulsion of the products of conception; mifepristone also has the pharmacologic effect of inducing uterine contractions and labor. Should the medication regimen fail to terminate a pregnancy as intended, the woman should be apprised of the potential fetal risks. The risk of adverse developmental outcomes with a continued pregnancy after a failed pregnancy termination with Mifepristone in a regimen with misoprostol is unknown; however, the process of a failed pregnancy termination could disrupt normal embryo-fetal development and result in adverse developmental effects. Cases of failed terminations and continued pregnancy should be reported to the manufacturer at: 1-855-MIFEINFO (1-855-643-3463). Conception can occur following termination and before resumption of normal menses, so appropriate contraception can be initiated as soon as the pregnancy termination has been confirmed, or before the woman resumes sexual intercourse.

    DEA CLASS

    Rx

    DESCRIPTION

    Synthetic steroid with potent antiprogesterone and antiglucocorticoid activity; derivative of the synthetic progestin norethindrone
    One product is used with a prostaglandin (e.g., misoprostol) as an abortifacent regimen via a restricted access program (Mifeprex)
    Another product (Korlym) is used to treat hyperglycemia in adults with Cushing’s syndrome and is available via a limited distribution program since use is contraindicated during pregnancy

    COMMON BRAND NAMES

    Korlym, Mifeprex

    HOW SUPPLIED

    Korlym/Mifeprex/Mifepristone (RU-486) Oral Tab: 200mg, 300mg

    DOSAGE & INDICATIONS

    For pregnancy termination in combination with misoprostol, through 70 days (10 weeks) gestation dated from the first day of the last menstrual period.
    Oral dosage (FDA-approved regimen)
    Adult females through 70 days (10 weeks) gestation

    On day 1, administer one 200 mg mifepristone tablet PO as a single dose. Between 24 to 48 hours later, administer misoprostol 800 mcg buccally; the patient should place two 200 mcg misoprostol tablets in each cheek pouch for 30 minutes and then swallow any remnants with water or another liquid. The duration of pregnancy may be determined from menstrual history and clinical examination. If the duration of pregnancy is uncertain or ectopic pregnancy is suspected, assess by ultrasonographic scan. Intrauterine devices (IUDs) should be removed prior to mifepristone treatment. Discuss an appropriate location for the patient to be when she takes misoprostol; expulsion could begin within 2 hours of administration, and typically occurs within 24 hours. Patients should be given emergency contact numbers for healthcare providers and instructed what to do if significant discomfort, excessive bleeding, or other adverse events occur. Follow-up assessment to confirm complete pregnancy termination and evaluate bleeding should occur approximately 7 to 14 days after mifepristone administration. If complete expulsion has not occurred, but the pregnancy is not ongoing, women may be treated with another dose of misoprostol 800 mcg buccally; a follow-up visit approximately 7 days later should occur to assess for complete termination.

    For the treatment of hyperglycemia secondary to endogenous Cushing's syndrome in patients who have type 2 diabetes mellitus or glucose intolerance and have failed surgery or are not candidates for surgery.
    Mifepristone has been designated an orphan drug for this indication by the FDA.
    Oral dosage (Korlym only)
    Adults

    Initially, 300 mg PO once daily with a meal. Increase dose in 300 mg increments, based on clinical response and tolerability. Do not increase more frequently than once every 2 to 4 weeks. Max: 1,200 mg/day and not to exceed 20 mg/kg/day PO. Review drug interactions and product label; specific dosage adjustments and a reduced max dosage are recommended based on the patient's current mifepristone dosage, response, and other treatments. Early symptom improvement, within 6 weeks, may guide dose escalation, later response may guide therapy beyond 2 months. If treatment is interrupted, reinitiate at 300 mg/day. If interruption of treatment is due to an adverse event, titrate to a dose lower than that which resulted in the interruption.

    For emergency postcoital contraception†.
    Oral dosage
    Adult females

    600 mg PO given within 72 hours of intercourse was 100% effective in preventing pregnancy and was superior to an estrogen-progestin regimen; adverse effects were less in the mifepristone group; alternatively, 10 mg PO as a single dose, given within 72 hours of intercourse was found to be as effective as a levonorgestrel regimen (1.5% pregnancy rate in both groups); adverse effects did not differ greatly between the treatment groups. Mid-level doses of 25 mg, 50 mg, and 100 mg PO of mifepristone have also been successful; pregnancy rates are comparable to the 10 mg dose. Higher doses are associated with a higher incidence in the delay of the start of menses, which may increase patient anxiety.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    200 mg PO as a single dose is the FDA-approved maximum dose for termination of pregnancy; 1,200 mg/day PO for Cushing's syndrome and not to exceed 20 mg/kg/day PO; otherwise maximum dose is dependent on the indication for use.

    Geriatric

    Safety and efficacy have not been established.

    Adolescents

    Safety and efficacy have not been established.

    Children

    Safety and efficacy have not been established.

    Infants

    Safety and efficacy have not been established.

    Neonates

    Safety and efficacy have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Mifeprex (termination of early pregnancy): The effects of hepatic impairment have not been investigated.
     
    Korlym (Cushing's disease treatment): Do not exceed 600 mg/day PO for mild to moderate hepatic impairment; patients with severe hepatic impairment have not been studied, therefore do not use.

    Renal Impairment

    Mifeprex (termination of early pregnancy): The effects of renal impairment have not been investigated.
     
    Korlym (Cushing's disease treatment)
    CrCl less than 90 mL/min: Do not exceed 600 mg/day PO in patients with renal impairment.

    ADMINISTRATION

    Oral Administration

    Termination of early pregnancy (Mifeprex)
    Administered orally as a single-dose in a healthcare clinic, medical office, or hospital. Prescribers must be certified with the Mifeprex REMS program by completing the Prescriber Agreement Form; state laws may dictate further restrictions and requirements. The drug is sold directly to approved physicians and is not available in pharmacies.
    Prior to administration, complete the Patient Agreement Form (informed consent) and confirm pregnancy duration. Provide patient with Mifepristone Medication Guide (required by US federal law) and inform her to take it with her if she visits an emergency room or healthcare provider who did not prescribe mifepristone.
    Record the serial number of the mifepristone package in the patient medical record to serve as a patient identification to maintain patient confidentiality.
    For purposes of this treatment, pregnancy is dated from the first day of the last menstrual period. Pregnancy duration may be determined from menstrual history and clinical examination. If the duration is uncertain or ectopic pregnancy is suspected, assess the pregnancy by ultrasonographic scan. 
    Remove any intrauterine device (IUD) prior to treatment with mifepristone.
    To complete the regimen, patients MUST take misoprostol within 24 to 48 hours after taking mifepristone.
    Discuss an appropriate location for the patient to be when she takes misoprostol; expulsion could begin within 2 hours of administration, and typically occurs within 24 hours. 
    Give the treated patient the emergency contact numbers for healthcare providers and instruct the patient what to do if significant discomfort, excessive bleeding, or other adverse events occur.
    Follow-up assessment to confirm complete pregnancy termination and evaluate bleeding should occur approximately 7 to 14 days after mifepristone administration. Termination can be confirmed by medical history, clinical examination, human Chorionic Gonadotropin (hCG) testing, or ultrasonographic scan. Lack of bleeding usually indicates treatment failure; however, prolonged or heavy bleeding is not proof of a complete abortion.
    If complete expulsion has not occurred, but the pregnancy is not ongoing, women may be treated with another dose of misoprostol; a follow-up visit approximately 7 days later should occur to assess for complete termination.
    Report failed terminations or other serious adverse reactions to the manufacturer.
    For more information, call the manufacturer at 1-877-432-7596 in the US 24 hours a day, 7 days a week.
     
    Cushing's syndrome (Korlym)
    Administered orally with food as a single daily dose.
    Patients should swallow the tablet whole. Do not split, crush, or chew tablets.
     
    Other indications (Korlym)
    If administering mifepristone chronically; administer orally with food at roughly the same time daily.
    Patients should swallow the tablet whole. Do not split, crush, or chew tablets.

    STORAGE

    Korlym:
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    Mifeprex:
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    Mifepristone is contraindicated in patients with a history of hypersensitivity to mifepristone. When used in a medical abortion regimen that requires administration with misoprostol, mifepristone (e.g., Mifeprex) is then also contraindicated in patients with a history of allergy to misoprostol or other prostaglandins. Allergic reactions including anaphylaxis, angioedema, rash, hives, and itching have occurred.

    Endometrial cancer, endometrial hyperplasia, vaginal bleeding

    Mifepristone use for Cushing's disease (e.g., Korlym) is contraindicated for use in female patients with a history of unexplained vaginal bleeding, endometrial cancer, or endometrial hyperplasia with atypia, due to the potential for mifepristone-induced hormonal and endometrial changes. Mifepristone promotes unopposed endometrial proliferation that may result in endometrium thickening, cystic dilatation of endometrial glands, and vaginal bleeding. Women who experience vaginal bleeding during chronic mifepristone treatment should be referred to a gynecologist for further evaluation.

    Bleeding, fever, infection, sepsis

    Mifepristone, when used for medical abortion (e.g., Mifeprex), has been associated with cases of serious bacterial infection, including, although rare, fatal sepsis and septic shock. Patients should promptly report heavy vaginal bleeding, fever, or abdominal pain following treatment. A sustained fever 100.4 degrees F or above for more than 4 hours, severe abdominal pain, pelvic tenderness, syncope, or prolonged heavy vaginal bleeding, more than 24 hours after a medical abortion may be an indication of infection and warrant intervention; however, practitioners should also be alert to atypical presentations including leukocytosis, tachycardia, hemoconcentration, and general malaise (including weakness, nausea, vomiting, or diarrhea). Ensure the patient knows who to call and what to do if she experiences any of these symptoms. Uterine bleeding is expected during medical abortion; however, prolonged heavy bleeding (soaking through 2 thick full-size sanitary pads per hour for 2 consecutive hours) may be a sign of incomplete medical abortion or other complications. Heavy vaginal bleeding after a medical abortion should prompt the patient to seek immediate medical attention. Serious bacterial infections and sepsis, including fatalities, have occurred following the use of mifepristone and vaginal misoprostol and have been reported in the U.S. Clostridium sordellii has been identified as the causative organism in some cases; none of these patients presented with a fever, but they did present with sinus tachycardia, low blood pressure, leukocytosis, and very high red blood cell counts. The patients also had other atypical symptoms including weakness, nausea/vomiting, or diarrhea with or without abdominal pain. No causal relationship has been established between these events and the mifepristone-misoprostol regimen for termination of pregnancy. Patients with endogenous Cushing's syndrome are at risk for opportunistic infection such as Pneumocystis jiroveci pneumonia (PCP) during mifepristone treatment. Patients may present with respiratory distress shortly after initiation of the drug. Appropriate diagnostic tests should be undertaken and treatment for Pneumocystis jiroveci should be considered.

    Contraception requirements, pregnancy, pregnancy testing, reproductive risk

    Mifepristone has potent antiprogestational effects that will result in the termination of pregnancy. Mifepristone for treatment of Cushing's syndrome (e.g., Korlym) is contraindicated in women who are pregnant. Exclude pregnancy before the initiation of treatment and advise the female patient of the reproductive risk. Pregnancy testing should occur, and female patients of childbearing potential should have a negative pregnancy test before starting the chronic use of mifepristone and such women also must have a repeat negative pregnancy test if the drug is discontinued for more than 14 days. There are contraception requirements for female patients of reproductive potential during chronic treatment with mifepristone; all female patients of childbearing potential should use non-hormonal contraceptives during treatment and for 1 month after stopping treatment, unless the patient has had a surgical sterilization, in which case no additional contraception is needed. Should a woman become pregnant while taking mifepristone chronically, the woman should be apprised of the potential fetal risk. There are no data that assess the risk of birth defects in women exposed to mifepristone during pregnancy. Available data limited to exposure following a single dose of mifepristone during pregnancy showed a higher rate of major birth defects compared to the general population comparator. Animal studies also indicate a potential for fetal harm. Medical abortion with mifepristone (e.g., Mifeprex) is indicated when the objective is termination of the pregnancy at 70 days gestation or less, but should not be used for termination of later pregnancy. Mifepristone disrupts pregnancy, leading to the expulsion of the products of conception; mifepristone also has the pharmacologic effect of inducing uterine contractions and labor. Should the medication regimen fail to terminate a pregnancy as intended, the woman should be apprised of the potential fetal risks. The risk of adverse developmental outcomes with a continued pregnancy after a failed pregnancy termination with Mifepristone in a regimen with misoprostol is unknown; however, the process of a failed pregnancy termination could disrupt normal embryo-fetal development and result in adverse developmental effects. Cases of failed terminations and continued pregnancy should be reported to the manufacturer at: 1-855-MIFEINFO (1-855-643-3463). Conception can occur following termination and before resumption of normal menses, so appropriate contraception can be initiated as soon as the pregnancy termination has been confirmed, or before the woman resumes sexual intercourse.

    Ectopic pregnancy

    Mifepristone (e.g., Mifeprex) is contraindicated for use if ectopic pregnancy is present. Do not use the mifepristone-misoprostol combination regimen in patients with confirmed or suspected ectopic pregnancy or undiagnosed adnexal mass; the drug treatment procedure will not be effective to terminate an ectopic pregnancy. Any abdominal pain should be evaluated prior to use and throughout the treatment period, as this may indicate ectopic pregnancy or may indicate an infectious process, which may be serious. The antiprogestin mifepristone has no direct effect on the cytotrophoblast. An undetected ectopic pregnancy may then rupture and cause serious morbidity. Because ectopic pregnancy may be present despite a practitioner's efforts to rule it out prior to use of the drug, the practitioner should consider the possibility of ectopic pregnancy throughout the treatment period and have a plan for its management.

    Contraceptive devices

    Any intrauterine contraceptive devices ('IUDs') should be removed before treatment with mifepristone (e.g., Mifeprex) begins as it is contraindicated to have an IUD in place during the termination of the pregnancy by this method.

    Incomplete abortion

    Because it is important to have access to appropriate medical care if an emergency develops, mifepristone (e.g., Mifeprex) should not be administered if a patient does not have adequate access to medical facilities equipped to provide emergency treatment of incomplete abortion, blood transfusions, surgery, and emergency resuscitation during the treatment period. Mifepristone should not be used by any patient who may be unable to understand the effects of the termination treatment procedure or to comply with its regimen or the required office visits. Patients should review the required Medication Guide and Patient Agreement Form and should be given a copy of the mifepristone label for review. Patients should discuss their understanding of these materials with their health care providers, and retain the Medication Guide for later reference. Patients should return for a follow-up visit at approximately 7 to 14 days after administration of mifepristone to confirm that the pregnancy is completely terminated. If complete expulsion has not occurred, and the pregnancy is not ongoing, another dose of misoprostol can be administered; however, there have been rare reports of uterine rupture in women receiving mifepristone and misoprostol, including women who received multiple doses of misoprostol within 24 hours. Women who choose a repeat dose of misoprostol should have a follow-up visit approximately 7 days later. The existence of debris in the uterus, if seen on ultrasonography, does not necessarily require surgical removal. Surgical evacuation is recommended in cases of ongoing pregnancies after failed medical abortion.

    Hepatic disease, renal failure, renal impairment

    Mifepristone (e.g., Korlym), when used in the treatment of Cushing's syndrome, should be used with caution in patients with renal impairment or renal failure, and in patients with mild to moderate hepatic impairment; maximum doses should not exceed 600 mg per day. The chronic use of mifepristone in patients with severe hepatic disease is not recommended. Due to an increased risk of adverse events due to reduced hepatic metabolism, mifepristone should be used with extreme caution in patients taking ketoconazole and other strong CYP3A inhibitors, as these could substantially increase the concentration of mifepristone in the blood. The benefit of concomitant use of these agents should be carefully weighed against the potential risks. If use of a strong CYP3A inhibitor is medically necessary, the daily adult mifepristone dose should be limited to 300 mg/day.

    Porphyria

    Mifepristone (e.g., Mifeprex) for pregnancy termination is contraindicated in patients with inherited porphyria due to the risk of worsening or precipitating attacks.

    Diabetes mellitus

    Mifepristone (e.g., Korlym) is for the treatment of hyperglycemia related to Cushing's syndrome. The drug should not be used in the treatment of patients with type 2 diabetes mellitus unless it is secondary to Cushing's syndrome. In patients with Cushing's syndrome, changes in glucose control, antidiabetic medication requirements or insulin levels may provide an early assessment of response (within 6 weeks) and may help guide early dose titration.

    Anticoagulant therapy, coagulopathy, hemophilia, immune thrombocytopenic purpura (ITP)

    Mifepristone (e.g., Mifeprex) is contraindicated for pregnancy termination in females taking anticoagulant therapy and those with hemorrhagic disorders, such as coagulopathy, hemophilia, or immune thrombocytopenic purpura (ITP), due to the risk for heavy bleeding. Use with caution in patients with pre-existing anemia. The use of mifepristone is assumed to require the same preventive measures as those taken prior to and during surgical abortion to prevent rhesus [Rho] immunization in Rho[D]-negative women exposed to Rho[D]-positive fetal blood. All patients should be scheduled for and return for a follow-up visit at approximately 7 to 14 days after administration of mifepristone to confirm that the pregnancy is completely terminated and evaluate the degree of bleeding. Termination can be confirmed by medical history, clinical examination, human Chorionic Gonadotropin (hCG) testing, or ultrasonographic scan. Lack of bleeding after treatment usually indicates medication failure; however, prolonged or heavy bleeding is not proof of a complete abortion. Prolonged, heavy vaginal bleeding (soaking through 2 thick full-size sanitary pads per hour for 2 consecutive hours) may be a sign of incomplete abortion or other complications; prompt medical and/or surgical intervention may be necessary. Patients should be instructed to seek immediate medical attention if they experience prolonged, heavy vaginal bleeding. Report hospitalization, blood transfusion, failed terminations, or other serious adverse events to the manufacturer 1-855-643-3463.[28003] When used chronically, mifepristone (e.g., Korlym) should be used with caution in women who have hemorrhagic disorders or are receiving concurrent anticoagulant therapy. Being an antagonist of the progesterone receptor, mifepristone promotes unopposed endometrial proliferation that may result in endometrium thickening, cystic dilatation of endometrial glands, and vaginal bleeding during chronic use. Women who experience unexplained vaginal bleeding during treatment should be referred to a gynecologist for further evaluation.[48697]

    Adrenal insufficiency, corticosteroid therapy, organ transplant

    The use of mifepristone in individuals on long-term corticosteroid therapy, such as patients with organ transplant, is considered contraindicated due to the potential risk of adrenal insufficiency. Mifepristone (e.g., Mifeprex) is contraindicated in patients with chronic adrenal failure due to a risk of acute renal insufficiency. During chronic use (e.g., Korlym therapy), monitor closely for signs and symptoms of adrenal insufficiency, including weakness, nausea, increased fatigue, hypotension, and hypoglycemia with chronic use. Discontinue mifepristone if adrenal insufficiency is suspected and administer glucocorticoids immediately; high doses and prolonged treatment may be necessary taking into account the long half-life of mifepristone (85 hours). After symptom resolution, re-instate mifepristone therapy at a lower dose with close monitoring.

    Hypokalemia

    During clinical trials for Cushing's syndrome, hypokalemia was observed during mifepristone (e.g., Korlym) therapy and can occur at any time during treatment. Hypokalemia should therefore be corrected before mifepristone treatment begins. In addition, monitor serum potassium 1 to 2 weeks following dose initiation or increase and periodically thereafter. Correct mifepristone-induced hypokalemia with intravenous or oral potassium supplementation based on clinical need. If hypokalemia persists in spite of potassium supplementation, consider adding mineralocorticoid antagonists. Hypokalemia may increase the risk of a prolonged QT interval due to the drug.

    Apheresis, AV block, bradycardia, cardiomyopathy, celiac disease, females, heart failure, human immunodeficiency virus (HIV) infection, hyperparathyroidism, hypocalcemia, hypomagnesemia, hypothermia, hypothyroidism, long QT syndrome, myocardial infarction, pheochromocytoma, QT prolongation, rheumatoid arthritis, sickle cell disease, sleep deprivation, stroke, systemic lupus erythematosus (SLE)

    Caution is warranted when mifepristone (e.g., Korlym) is used chronically in patients with underlying cardiac disease including heart failure and coronary artery disease. Mifepristone does not reduce serum cortisol levels; elevated cortisol levels may activate mineralocorticoid receptors which are also expressed in cardiac tissues. Mifepristone produces QT prolongation in a dose-related manner. Use mifepristone with caution in patients with conditions that may increase the risk of QT prolongation including congenital long QT syndrome, bradycardia, AV block, heart failure, stress-related cardiomyopathy, myocardial infarction, stroke, hypomagnesemia, hypokalemia, hypocalcemia, or in patients receiving medications known to prolong the QT interval or cause electrolyte imbalances. Females, people 65 years and older, patients with sleep deprivation, pheochromocytoma, sickle cell disease, hypothyroidism, hyperparathyroidism, hypothermia, systemic inflammation (e.g., human immunodeficiency virus (HIV) infection, fever, and some autoimmune diseases including rheumatoid arthritis, systemic lupus erythematosus (SLE), and celiac disease) and patients undergoing apheresis procedures (e.g., plasmapheresis [plasma exchange], cytapheresis) may also be at increased risk for QT prolongation. No research has been conducted to determine the effect of high dose exposure, concomitant dosing with other QT-prolonging drugs, or potassium channel variants resulting in a long QT interval. Therefore, administer mifepristone at the lowest effective dose and monitor for adverse cardiac events. There are no data on the safety and efficacy of mifepristone in women with chronic medical conditions such as cardiac disease or hypertension, as these patients were generally excluded from clinical trials for pregnancy termination.     

    Breast-feeding

    Mifepristone is present in human milk. Limited data demonstrate undetectable to low levels of the drug in human milk with the relative weight-adjusted infant dose 0.5% or less as compared to maternal dosing. The effects in a nursing infant or on milk production are unknown. The drug's antiprogestogen and glucocorticoid antagonist effects could be harmful to a nursing infant. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. To minimize exposure to a breastfed infant, women who discontinue or interrupt chronic mifepristone treatment may consider pumping and discarding breast milk during treatment and for 18 to 21 days (5 to 6 half-lives) after the last dose, before breast-feeding.

    Geriatric

    Clinical studies with mifepristone (e.g., Korlym) for the treatment of Cushing's syndrome did not include sufficient numbers of geriatric patients aged 65 years of age and older to determine whether they respond differently than younger people. In general, dose selection and escalation for an elderly patient should be cautious, due to the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. Geriatric patients may be at increased risk for QT prolongation when using mifepristone. Due to the indication for use, mifepristone (e.g., Mifeprex) is not indicated for use in geriatric females.

    ADVERSE REACTIONS

    Severe

    infection / Delayed / 0.2-1.0
    fetal death / Delayed / Incidence not known
    endometritis / Early / Incidence not known
    anaphylactoid reactions / Rapid / Incidence not known
    toxic epidermal necrolysis / Delayed / Incidence not known
    angioedema / Rapid / Incidence not known
    teratogenesis / Delayed / Incidence not known

    Moderate

    hypokalemia / Delayed / 34.0-44.0
    peripheral edema / Delayed / 26.0-26.0
    hypertension / Early / 24.0-24.0
    dyspnea / Early / 16.0-16.0
    constipation / Delayed / 10.0-10.0
    hypoglycemia / Early / 5.0-10.0
    edema / Delayed / 5.0-10.0
    myasthenia / Delayed / 5.0-10.0
    adrenocortical insufficiency / Delayed / 4.0-4.0
    vaginal bleeding / Delayed / 10.0
    uterine contractions / Early / 10.0
    anemia / Delayed / Incidence not known
    bleeding / Early / Incidence not known
    stomatitis / Delayed / Incidence not known
    endometrial hyperplasia / Delayed / Incidence not known
    hot flashes / Early / Incidence not known
    palpitations / Early / Incidence not known
    orthostatic hypotension / Delayed / Incidence not known
    sinus tachycardia / Rapid / Incidence not known
    hypotension / Rapid / Incidence not known

    Mild

    abdominal pain / Early / 5.0-96.0
    nausea / Early / 48.0-75.0
    fever / Early / 48.0-48.0
    vomiting / Early / 26.0-48.0
    fatigue / Early / 0-48.0
    headache / Early / 2.0-44.0
    diarrhea / Early / 12.0-43.0
    dizziness / Early / 9.0-41.0
    xerostomia / Early / 18.0-18.0
    sinusitis / Delayed / 14.0-14.0
    pharyngitis / Delayed / 12.0-12.0
    anorexia / Delayed / 10.0-10.0
    polydipsia / Early / 5.0-10.0
    gastroesophageal reflux / Delayed / 5.0-10.0
    malaise / Early / 5.0-10.0
    insomnia / Early / 5.0-10.0
    anxiety / Delayed / 0-10.0
    asthenia / Delayed / 1.0-10.0
    pruritus / Rapid / 4.0-4.0
    maculopapular rash / Early / 4.0-4.0
    pelvic pain / Delayed / Incidence not known
    leukocytosis / Delayed / Incidence not known
    chills / Rapid / Incidence not known
    dyspepsia / Early / Incidence not known
    urticaria / Rapid / Incidence not known
    rash / Early / Incidence not known
    menstrual irregularity / Delayed / Incidence not known
    emotional lability / Early / Incidence not known
    syncope / Early / Incidence not known

    DRUG INTERACTIONS

    Abemaciclib: (Major) If coadministration with mifepristone is necessary, reduce the dose of abemaciclib to 100 mg PO twice daily in patients on either of the recommended starting doses of either 200 mg or 150 mg twice daily. In patients who have had already had a dose reduction to 100 mg twice daily due to adverse reactions, further reduce the dose of abemaciclib to 50 mg PO twice daily. Discontinue abemaciclib for patients unable to tolerate 50 mg twice daily. If mifepristone is discontinued, increase the dose of abemaciclib to the original dose after 3 to 5 half-lives of mifepristone. Abemaciclib is a CYP3A4 substrate and mifepristone is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by 2.5-fold in cancer patients. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
    Acalabrutinib: (Major) Avoid use of these drugs together if possible. Significantly increased acalabrutinib exposure may occur when mifepristone is used chronically in the treatment of hormonal conditions, such as Cushing's syndrome. If mifepristone use is unavoidable, limit the dose of acalabrutinib to 100 mg once daily and monitor closely for drug-related toxicity and need for further adjustment or interruption of acalbrutinib therapy. Acalabrutinib is a CYP3A4 substrate; mifepristone is a CYP3A4 inhibitor. Mifepristone is expected to increase the exposure of CYP3A4 substrates. Due to the slow elimination of mifepristone from the body, any drug interactions that occur may be prolonged.
    Acetaminophen; Butalbital; Caffeine; Codeine: (Moderate) Concomitant use of codeine with chronic mifepristone therapy may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of mifepristone could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If mifepristone is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Mifepristone is a strong inhibitor of CYP3A4. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
    Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Concomitant use of dihydrocodeine with chronic mifepristone therapy may increase dihydrocodeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased dihydromorphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of dihydrocodeine until stable drug effects are achieved. Discontinuation of mifepristone could decrease dihydrocodeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to dihydrocodeine. If mifepristone is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Mifepristone is a strong inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
    Acetaminophen; Codeine: (Moderate) Concomitant use of codeine with chronic mifepristone therapy may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of mifepristone could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If mifepristone is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Mifepristone is a strong inhibitor of CYP3A4. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
    Acetaminophen; Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if chronic, concurrent use of mifepristone is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like mifepristone can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If mifepristone is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
    Acetaminophen; Oxycodone: (Moderate) Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression and sedation if concurrent use of mifepristone is necessary. If mifepristone is discontinued, consider increasing the oxycodone dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oxycodone is a CYP3A4 substrate, and coadministration with a strong CYP3A4 inhibitor like mifepristone can increase oxycodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of oxycodone. If mifepristone is discontinued, oxycodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to oxycodone. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
    Ado-Trastuzumab emtansine: (Major) Avoid coadministration of mifepristone with ado-trastuzumab emtansine if possible due to the risk of elevated exposure to the cytotoxic component of ado-trastuzumab emtansine, DM1. Delay ado-trastuzumab emtansine treatment until mifepristone has cleared from the circulation (approximately 3 half-lives of mifepristone) when possible. If concomitant use is unavoidable, closely monitor patients for ado-trastuzumab emtansine-related adverse reactions. The cytotoxic component of ado-trastuzumab emtansine, DM1, is metabolized mainly by CYP3A4 and to a lesser extent by CYP3A5; mifepristone is a strong CYP3A4 inhibitor. Formal drug interaction studies with ado-trastuzumab emtansine have not been conducted. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
    Afatinib: (Moderate) If the concomitant use of mifepristone and afatinib is necessary, monitor for afatinib-related adverse reactions. If the original dose of afatinib is not tolerated, consider reducing the daily dose of afatinib by 10 mg; resume the previous dose of afatinib as tolerated after discontinuation of mifepristone. The manufacturer of afatinib recommends permanent discontinuation of therapy for severe or intolerant adverse drug reactions at a dose of 20 mg per day, but does not address a minimum dose otherwise. Afatinib is a P-glycoprotein (P-gp) substrate and mifepristone is a P-gp inhibitor; coadministration may increase plasma concentrations of afatinib. Administration with another P-gp inhibitor, given 1 hour before a single dose of afatinib, increased afatinib exposure by 48%; there was no change in afatinib exposure when the P-gp inhibitor was administered at the same time as afatinib or 6 hours later. In healthy subjects, the relative bioavailability for AUC and Cmax of afatinib was 119% and 104%, respectively, when coadministered with the same P-gp inhibitor, and 111% and 105% when the inhibitor was administered 6 hours after afatinib.
    Alfentanil: (Major) Coadministration of alfentanil is contraindicated when mifepristone is used chronically, such as in the treatment of Cushing's syndrome or other hormonal conditions. Mifepristone inhibits CYP3A4. Coadministration of mifepristone may lead to a significant increase in serum concentrations of drugs that are CYP3A4 substrates and that have a narrow therapeutic index, such as alfentanil. The increase in alfentanil concentrations can increase the risk for serious CNS depression and respiratory depression, particularly when mifepristone is added after a stable dose of alfentanil is achieved. A reduced dosage of alfentanil may be necessary if use together is not avoidable. Due to the slow elimination of mifepristone from the body, such interactions may be observed for a prolonged period after mifepristone administration.
    Alfuzosin: (Contraindicated) Alfuzosin is contraindicated for use with mifepristone due to the potential for serious/life-threatening reactions, including hypotension. Additive effects on the QT interval may also occur. Coadministration is expected to reduce the metabolism and increase systemic exposure to alfuzosin. Alfuzosin is a CYP3A4 substrate that has been associated with dose-dependent QT prolongation; mifepristone is a strong CYP3A4 inhibitor that has also been associated with dose-dependent prolongation of the QT interval. Coadministration of another strong CYP3A4 inhibitor increased the alfuzosin AUC by 2.5-fold to 3.2-fold.
    Aliskiren; Amlodipine: (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with mifepristone is necessary; adjust the dose of amlodipine as clinically appropriate. Mifepristone is a strong CYP3A inhibitor and amlodipine is a CYP3A substrate. Coadministration with a moderate CYP3A4 inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. Strong CYP3A4 inhibitors may increase the plasma concentrations of amlodipine to a greater extent.
    Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with mifepristone is necessary; adjust the dose of amlodipine as clinically appropriate. Mifepristone is a strong CYP3A inhibitor and amlodipine is a CYP3A substrate. Coadministration with a moderate CYP3A4 inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. Strong CYP3A4 inhibitors may increase the plasma concentrations of amlodipine to a greater extent.
    Almotriptan: (Moderate) The maximum recommended starting dose of almotriptan is 6.25 mg if coadministration with mifepristone in adults receiving mifepristone chronically for the treatment of hormonal conditions is necessary; do not exceed 12.5 mg within a 24-hour period. Concomitant use of almotriptan and mifepristone should be avoided in patients with renal or hepatic impairment. Almotriptan is a CYP3A4 substrate and mifepristone is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased almotriptan exposure by approximately 60%. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
    Alprazolam: (Contraindicated) Coadministration of mifepristone and alprazolam is contraindicated due to the potential for elevated alprazolam concentrations, which may cause prolonged sedation and respiratory depression. Lorazepam, oxazepam, or temazepam may be safer alternatives if a benzodiazepine must be administered in combination with mifepristone, as these benzodiazepines are not oxidatively metabolized. Alprazolam is a CYP3A4 substrate and mifepristone is a strong CYP3A4 inhibitor. Coadministration with other strong CYP3A4 inhibitors increased alprazolam exposure by 2.7- to 3.98-fold.
    Amiodarone: (Major) Avoid use of mifepristone with QT interval prolonging drugs. Mifepristone has been associated with dose-dependent prolongation of the QT interval. There is no experience with high exposure or concomitant use with other QT prolonging drugs. To minimize the risk of QT prolongation, the lowest effective dose should always be used. Although specific drug interactions with mifepristone have not been studied, the use of mifepristone with CYP3A inhibitors may result in increased mifepristone concentrations and an increased risk of QT prolongation. Amiodarone is a CYP3A4 inhibitor and is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone.
    Amisulpride: (Major) Monitor ECG and use the lowest effective dose of mifepristone if amisulpride is coadministered due to the potential for additive QT prolongation. Amisulpride causes dose- and concentration- dependent QT prolongation. Mifepristone has been associated with dose-dependent prolongation of the QT interval.
    Amitriptyline: (Minor) Due to a possible risk for QT prolongation and torsade de pointes (TdP), mifepristone and tricyclic antidepressants should be used together cautiously. Mifepristone has been associated with dose-dependent prolongation of the QT interval. There is no experience with high exposure or concomitant use with other QT prolonging drugs. To minimize the risk of QT prolongation, the lowest effective dose should always be used. Drugs with a possible risk for QT prolongation and torsades de pointes that should be used cautiously with mifepristone include tricyclic antidepressants.
    Amitriptyline; Chlordiazepoxide: (Minor) Due to a possible risk for QT prolongation and torsade de pointes (TdP), mifepristone and tricyclic antidepressants should be used together cautiously. Mifepristone has been associated with dose-dependent prolongation of the QT interval. There is no experience with high exposure or concomitant use with other QT prolonging drugs. To minimize the risk of QT prolongation, the lowest effective dose should always be used. Drugs with a possible risk for QT prolongation and torsades de pointes that should be used cautiously with mifepristone include tricyclic antidepressants.
    Amlodipine: (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with mifepristone is necessary; adjust the dose of amlodipine as clinically appropriate. Mifepristone is a strong CYP3A inhibitor and amlodipine is a CYP3A substrate. Coadministration with a moderate CYP3A4 inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. Strong CYP3A4 inhibitors may increase the plasma concentrations of amlodipine to a greater extent.
    Amlodipine; Atorvastatin: (Moderate) Coadministration of mifepristone may lead to an increase in serum levels of atorvastatin. Due to the slow elimination of mifepristone from the body, such interactions may be observed for a prolonged period after mifepristone administration. Mifepristone inhibits CYP3A4; atorvastatin is a CYP3A4 substrate. Monitor closely for "statin" related side effects, such as myopathy. The dose of atorvastatin, when administered with a strong CYP3A4 inhibitor, should not exceed 40 mg/day. (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with mifepristone is necessary; adjust the dose of amlodipine as clinically appropriate. Mifepristone is a strong CYP3A inhibitor and amlodipine is a CYP3A substrate. Coadministration with a moderate CYP3A4 inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. Strong CYP3A4 inhibitors may increase the plasma concentrations of amlodipine to a greater extent.
    Amlodipine; Benazepril: (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with mifepristone is necessary; adjust the dose of amlodipine as clinically appropriate. Mifepristone is a strong CYP3A inhibitor and amlodipine is a CYP3A substrate. Coadministration with a moderate CYP3A4 inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. Strong CYP3A4 inhibitors may increase the plasma concentrations of amlodipine to a greater extent.
    Amlodipine; Celecoxib: (Moderate) Mifepristone significantly increased exposure of drugs metabolized by CYP2C8/2C9 in interaction studies. Therefore, when mifepristone is used chronically, as in the treatment of Cushing's syndrome, use caution with coadministered CYP2C8/2C9 substrates, including the NSAIDs. Use the lowest doses of the substrate and patients should be monitored closely for adverse reactions. (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with mifepristone is necessary; adjust the dose of amlodipine as clinically appropriate. Mifepristone is a strong CYP3A inhibitor and amlodipine is a CYP3A substrate. Coadministration with a moderate CYP3A4 inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. Strong CYP3A4 inhibitors may increase the plasma concentrations of amlodipine to a greater extent.
    Amlodipine; Hydrochlorothiazide, HCTZ; Olmesartan: (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with mifepristone is necessary; adjust the dose of amlodipine as clinically appropriate. Mifepristone is a strong CYP3A inhibitor and amlodipine is a CYP3A substrate. Coadministration with a moderate CYP3A4 inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. Strong CYP3A4 inhibitors may increase the plasma concentrations of amlodipine to a greater extent.
    Amlodipine; Olmesartan: (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with mifepristone is necessary; adjust the dose of amlodipine as clinically appropriate. Mifepristone is a strong CYP3A inhibitor and amlodipine is a CYP3A substrate. Coadministration with a moderate CYP3A4 inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. Strong CYP3A4 inhibitors may increase the plasma concentrations of amlodipine to a greater extent.
    Amlodipine; Telmisartan: (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with mifepristone is necessary; adjust the dose of amlodipine as clinically appropriate. Mifepristone is a strong CYP3A inhibitor and amlodipine is a CYP3A substrate. Coadministration with a moderate CYP3A4 inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. Strong CYP3A4 inhibitors may increase the plasma concentrations of amlodipine to a greater extent.
    Amlodipine; Valsartan: (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with mifepristone is necessary; adjust the dose of amlodipine as clinically appropriate. Mifepristone is a strong CYP3A inhibitor and amlodipine is a CYP3A substrate. Coadministration with a moderate CYP3A4 inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. Strong CYP3A4 inhibitors may increase the plasma concentrations of amlodipine to a greater extent.
    Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with mifepristone is necessary; adjust the dose of amlodipine as clinically appropriate. Mifepristone is a strong CYP3A inhibitor and amlodipine is a CYP3A substrate. Coadministration with a moderate CYP3A4 inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. Strong CYP3A4 inhibitors may increase the plasma concentrations of amlodipine to a greater extent.
    Amoxicillin; Clarithromycin; Lansoprazole: (Major) Avoid coadministration of mifepristone with clarithromycin due to the risk of additive QT prolongation and torsade de pointes (TdP); the exposure of both drugs may also be increased. If concomitant use of mifepristone is necessary for the treatment of Cushing's syndrome in a patient already receiving clarithromycin, initiate mifepristone at a dose of 300 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with clarithromycin is initiated in a patient already receiving mifepristone 300 mg, dosage adjustments are not required. If therapy with clarithromycin is initiated in a patient already receiving mifepristone 600 mg, reduce dose of mifepristone to 300 mg and titrate to a maximum of 600 mg if clinically indicated. If therapy with clarithromycin is initiated in a patient already receiving 900 mg, reduce dose of mifepristone to 600 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with clarithromycin is initiated in a patient already receiving 1,200 mg, reduce the mifepristone dose to 900 mg. Both mifepristone and clarithromycin are substrates and strong inhibitors of CYP3A4 that are associated with QT prolongation.
    Amoxicillin; Clarithromycin; Omeprazole: (Major) Avoid coadministration of mifepristone with clarithromycin due to the risk of additive QT prolongation and torsade de pointes (TdP); the exposure of both drugs may also be increased. If concomitant use of mifepristone is necessary for the treatment of Cushing's syndrome in a patient already receiving clarithromycin, initiate mifepristone at a dose of 300 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with clarithromycin is initiated in a patient already receiving mifepristone 300 mg, dosage adjustments are not required. If therapy with clarithromycin is initiated in a patient already receiving mifepristone 600 mg, reduce dose of mifepristone to 300 mg and titrate to a maximum of 600 mg if clinically indicated. If therapy with clarithromycin is initiated in a patient already receiving 900 mg, reduce dose of mifepristone to 600 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with clarithromycin is initiated in a patient already receiving 1,200 mg, reduce the mifepristone dose to 900 mg. Both mifepristone and clarithromycin are substrates and strong inhibitors of CYP3A4 that are associated with QT prolongation.
    Amprenavir: (Major) Caution is advised when administering amprenavir with mifepristone because increased serum concentrations of either drug may occur. When mifepristone is used in the treatment of Cushing's syndrome, coadministration with amprenavir should be done only when necessary, and in such cases the dose of mifepristone should be limited to a maximum dose of 900 mg per day. In a patient already receiving amprenavir, initiate mifepristone at a dose of 300 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with amprenavir is initiated in a patient already receiving mifepristone 300 mg, dosage adjustments are not required. If therapy with amprenavir is initiated in a patient already receiving mifepristone 600 mg, reduce dose of mifepristone to 300 mg and titrate to a maximum of 600 mg if clinically indicated. If therapy with amprenavir is initiated in a patient already receiving 900 mg, reduce dose of mifepristone to 600 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with amprenavir is initiated in a patient already receiving 1,200 mg, reduce the mifepristone dose to 900 mg. Both mifepristone and amprenavir are substrates and strong inhibitors of CYP3A4.
    Anagrelide: (Major) Torsades de pointes (TdP) and ventricular tachycardia have been reported with anagrelide. In addition, dose-related increases in mean QTc and heart rate were observed in healthy subjects. A cardiovascular examination, including an ECG, should be obtained in all patients prior to initiating anagrelide therapy. Monitor patients during anagrelide therapy for cardiovascular effects and evaluate as necessary. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with anagrelide include mifepristone.
    Antithrombin III: (Major) When mifepristone, is used for the termination of pregnancy, concurrent use of anticoagulants is contraindicated due to the increased risk of serious bleeding. When mifepristone is used for Cushing's disease or hormonal conditions, concurrent use of some anticoagulants should be approached with caution, but no particular precautions are necessary with Antithrombin III; monitor as usual for signs or symptoms of bleeding.
    Apalutamide: (Major) Avoid coadministration of mifepristone (Korlym) with apalutamide due to possible decreases in the plasma concentrations of mifepristone; exposure to apalutamide may also increase. The impact of apalutamide on the efficacy of short-term mifepristone for termination of pregnancy is unknown; refer to the follow-up assessment to verify that treatment has been successful. Mifepristone is a CYP3A4 substrate and apalutamide is a strong CYP3A4 inducer. The concomitant use of CYP3A4 inducers with mifepristone has not been studied.
    Apixaban: (Major) When mifepristone is used for the termination of pregnancy, concurrent use of anticoagulants is contraindicated due to the increased risk of serious bleeding. When mifepristone is used for the treatment of Cushing's disease or other hormonal conditions, reduce the apixaban dose by 50%. If patients are already receiving 2.5 mg twice daily, avoid concomitant administration. Mifepristone is a combined P-gp and CYP3A4 inhibitor and concomitant administration may result in increased exposure to apixaban and an increase in the risk of bleeding. If active pathological bleeding occurs, apixaban should be discontinued. Due to the long duration of action of mifepristone, any drug interaction that occurs may be prolonged.
    Apomorphine: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), mifepristone and apomorphine should be used together cautiously. Mifepristone has been associated with dose-dependent prolongation of the QT interval. There is no experience with high exposure or concomitant use with other QT prolonging drugs. To minimize the risk of QT prolongation, the lowest effective dose should always be used. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
    Aprepitant, Fosaprepitant: (Major) The manufacturer of aprepitant recommends avoiding the concomitant use of mifepristone with aprepitant due to substantially increased exposure of aprepitant; increased mifepristone exposure may also occur. If coadministration cannot be avoided, use caution and monitor for an increase in mifepristone- and aprepitant-related adverse effects for several days after administration of a multi-day aprepitant regimen. When mifepristone is used in the treatment of Cushing's syndrome and coadministered with drugs that inhibit CYP3A4, it is recommended to limit the dose of mifepristone to 300 mg/day. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown. In vitro, mifepristone is a CYP3A4 inhibitor and aprepitant is a CYP3A4 substrate. Mifepristone is also a CYP3A4 substrate. Aprepitant, when administered as a 3-day oral regimen (125 mg/80 mg/80 mg), is a moderate CYP3A4 inhibitor and inducer and may increase plasma concentrations of mifepristone. After administration, fosaprepitant is rapidly converted to aprepitant and shares many of the same drug interactions. However, as a single 150 mg intravenous dose regimen, fosaprepitant only weakly inhibits CYP3A4 for a duration of 2 days; there is no evidence of CYP3A4 induction.
    Ardeparin: (Major) When mifepristone is used for the termination of pregnancy, concurrent use of anticoagulants is contraindicated due to the increased risk of serious bleeding. Consider an alternative to mifepristone in these circumstances. When mifepristone is used chronically for other conditions, such as Cushing's disease, an interaction with low-molecular weight heparins is not expected; however, follow usual cautions and monitor as per standard of care.
    Aripiprazole: (Major) Because both mifepristone and aripiprazole are associated with a possible risk for QT prolongation and torsade de pointes (TdP), the combination should be used cautiously and with close monitoring. In addition, coadministration of mifepristone, a potent CYP3A4 inhibitor, with aripiprazole, a partial CYP3A4 substrate, may result in an elevated aripiprazole plasma concentrations and an increased risk for adverse events, including QT prolongation. If these drugs must be used together, the manufacturer recommends the oral dose of aripiprazole dose be reduced to one-half of the usual dose. In adults receiving 300 mg or 400 mg of Abilify Maintena, dose reductions to 200 mg or 300 mg, respectively, are recommended if the CYP3A4 inhibitor is used for more than 14 days. In adults receiving Aristada, the Aristada dose should be reduced to the next lower strength during use of a strong CYP3A4 inhibitor for more than 14 days. For patients receiving 882 mg of Aristada every 6 weeks or 1,064 mg every 2 months, the next lower strength should be 441 mg administered every 4 weeks. No dosage adjustment is necessary in patients taking 441 mg IM of Aristada, if tolerated. Because aripiprazole is also metabolized by CYP2D6, patients classified as CYP2D6 poor metabolizers (PMs) who are receiving a strong CYP3A4 inhibitor or patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor should have their oral aripiprazole dose reduced to one-quarter (25%) of the usual dose with subsequent adjustments based upon clinical response. Adults receiving Abilify Maintena who are PMs and receiving a strong CYP3A4 inhibitor should have a dose reduction to 200 mg/month IM. Patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their Abilify Maintena dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively. Adults receiving Aristada who are PMs of CYP2D6 and receiving a strong CYP3A4 inhibitor for more than 14 days should have their dose reduced from 662 mg, 882 mg, or 1,064 mg to 441 mg IM; no dose adjustment is needed in patients receiving 441 mg of Aristada, if tolerated. In adults receiving Aristada 662 mg, 882 mg, or 1,064 mg, combined use of a strong CYP2D6 inhibitor and a strong CYP3A4 inhibitor for more than 14 days should be avoided; no dose adjustment is needed in patients taking 441 mg, if tolerated. Avoid concurrent use of Aristada Initio and strong CYP3A4 inhibitors because the dose of Aristada Initio cannot be modified.
    Arsenic Trioxide: (Major) Avoid concomitant use of arsenic trioxide with other drugs that may cause QT interval prolongation, such as mifepristone; discontinue or select an alternative drug that does not prolong the QT interval prior to starting arsenic trioxide therapy. If concomitant drug use is unavoidable, frequently monitor electrocardiograms. Torsade de pointes (TdP), QT interval prolongation, and complete atrioventricular block have been reported with arsenic trioxide use. Mifepristone has been associated with dose-dependent prolongation of the QT interval. There is no experience with high exposure or concomitant use with other QT prolonging drugs. To minimize the risk of QT prolongation, the lowest effective dose should always be used.
    Artemether; Lumefantrine: (Major) Avoid use of mifepristone with artemether; lumefantrine if possible due to increased aremether; lumefantrine exposure and the potential for resultant drug toxicity, including QT prolongation. ECG monitoring is advised if use of drugs that prolong the QT interval is medically required. Both artemether; lumefantrine and mifepristone are associated with QT prolongation. Mifepristone, when used chronically for hormonal conditions such as Cushing's syndrome, is a CYP3A4 inhibitor and is expected to significantly increase the exposure to CYP3A4 substrates, including both artemether and lumefantrine. (Moderate) Avoid use of mifepristone with artemether; lumefantrine if possible due to increased aremether; lumefantrine exposure and the potential for resultant drug toxicity, including QT prolongation. ECG monitoring is advised if use of drugs that prolong the QT interval is medically required. Both artemether; lumefantrine and mifepristone are associated with QT prolongation. Mifepristone, when used chronically for hormonal conditions such as Cushing's syndrome, is a CYP3A4 inhibitor and is expected to significantly increase the exposure to CYP3A4 substrates, including both artemether and lumefantrine.
    Asenapine: (Moderate) Due to a possible risk for QT prolongation and torsade de pointes (TdP), mifepristone and asenapine should be used together cautiously. Mifepristone has been associated with dose-dependent prolongation of the QT interval. There is no experience with high exposure or concomitant use with other QT prolonging drugs. To minimize the risk of QT prolongation, the lowest effective dose should always be used. Asenapine has been associated with QT prolongation. According to the manufacturer of asenapine, the drug should be avoided in combination with other agents also known to have this effect.
    Aspirin, ASA; Butalbital; Caffeine; Codeine: (Moderate) Concomitant use of codeine with chronic mifepristone therapy may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of mifepristone could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If mifepristone is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Mifepristone is a strong inhibitor of CYP3A4. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
    Aspirin, ASA; Caffeine; Dihydrocodeine: (Moderate) Concomitant use of dihydrocodeine with chronic mifepristone therapy may increase dihydrocodeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased dihydromorphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of dihydrocodeine until stable drug effects are achieved. Discontinuation of mifepristone could decrease dihydrocodeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to dihydrocodeine. If mifepristone is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Mifepristone is a strong inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
    Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Concomitant use of codeine with chronic mifepristone therapy may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of mifepristone could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If mifepristone is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Mifepristone is a strong inhibitor of CYP3A4. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
    Aspirin, ASA; Oxycodone: (Moderate) Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression and sedation if concurrent use of mifepristone is necessary. If mifepristone is discontinued, consider increasing the oxycodone dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oxycodone is a CYP3A4 substrate, and coadministration with a strong CYP3A4 inhibitor like mifepristone can increase oxycodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of oxycodone. If mifepristone is discontinued, oxycodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to oxycodone. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
    Atazanavir: (Major) Caution is advised when administering atazanavir with mifepristone because increased serum concentrations of either drug may occur. When mifepristone is used in the treatment of Cushing's syndrome, coadministration with atazanavir should be done only when necessary, and in such cases the dose of mifepristone should be limited to a maximum dose of 900 mg per day. In a patient already receiving atazanavir, initiate mifepristone at a dose of 300 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with atazanavir is initiated in a patient already receiving mifepristone 300 mg, dosage adjustments are not required. If therapy with atazanavir is initiated in a patient already receiving mifepristone 600 mg, reduce dose of mifepristone to 300 mg and titrate to a maximum of 600 mg if clinically indicated. If therapy with atazanavir is initiated in a patient already receiving 900 mg, reduce dose of mifepristone to 600 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with atazanavir is initiated in a patient already receiving 1,200 mg, reduce the mifepristone dose to 900 mg. Both mifepristone and atazanavir are substrates and strong inhibitors of CYP3A4.
    Atazanavir; Cobicistat: (Major) Caution is advised when administering atazanavir with mifepristone because increased serum concentrations of either drug may occur. When mifepristone is used in the treatment of Cushing's syndrome, coadministration with atazanavir should be done only when necessary, and in such cases the dose of mifepristone should be limited to a maximum dose of 900 mg per day. In a patient already receiving atazanavir, initiate mifepristone at a dose of 300 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with atazanavir is initiated in a patient already receiving mifepristone 300 mg, dosage adjustments are not required. If therapy with atazanavir is initiated in a patient already receiving mifepristone 600 mg, reduce dose of mifepristone to 300 mg and titrate to a maximum of 600 mg if clinically indicated. If therapy with atazanavir is initiated in a patient already receiving 900 mg, reduce dose of mifepristone to 600 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with atazanavir is initiated in a patient already receiving 1,200 mg, reduce the mifepristone dose to 900 mg. Both mifepristone and atazanavir are substrates and strong inhibitors of CYP3A4. (Major) Caution is advised when administering cobicistat with mifepristone because increased serum concentrations of either drug may occur. When mifepristone is used in the treatment of Cushing's syndrome, coadministration with cobicistat should be done only when necessary, and in such cases the dose of mifepristone should be limited to a maximum dose of 900 mg per day. In a patient already receiving cobicistat, initiate mifepristone at a dose of 300 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with cobicistat is initiated in a patient already receiving mifepristone 300 mg, dosage adjustments are not required. If therapy with cobicistat is initiated in a patient already receiving mifepristone 600 mg, reduce dose of mifepristone to 300 mg and titrate to a maximum of 600 mg if clinically indicated. If therapy with cobicistat is initiated in a patient already receiving 900 mg, reduce dose of mifepristone to 600 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with cobicistat is initiated in a patient already receiving 1,200 mg, reduce the mifepristone dose to 900 mg. Both mifepristone and cobicistat are substrates and strong inhibitors of CYP3A4.
    Atomoxetine: (Moderate) Mifepristone has been associated with dose-dependent prolongation of the QT interval. There is no experience with high exposure or concomitant use with other QT prolonging drugs. To minimize the risk of QT prolongation, the lowest effective dose should always be used. Drugs with a possible risk for QT prolongation and torsades de pointes that should be used cautiously with mifepristone include atomoxetine. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose. Atomoxetine is considered a drug with a possible risk of TdP.
    Atorvastatin: (Moderate) Coadministration of mifepristone may lead to an increase in serum levels of atorvastatin. Due to the slow elimination of mifepristone from the body, such interactions may be observed for a prolonged period after mifepristone administration. Mifepristone inhibits CYP3A4; atorvastatin is a CYP3A4 substrate. Monitor closely for "statin" related side effects, such as myopathy. The dose of atorvastatin, when administered with a strong CYP3A4 inhibitor, should not exceed 40 mg/day.
    Atorvastatin; Ezetimibe: (Moderate) Coadministration of mifepristone may lead to an increase in serum levels of atorvastatin. Due to the slow elimination of mifepristone from the body, such interactions may be observed for a prolonged period after mifepristone administration. Mifepristone inhibits CYP3A4; atorvastatin is a CYP3A4 substrate. Monitor closely for "statin" related side effects, such as myopathy. The dose of atorvastatin, when administered with a strong CYP3A4 inhibitor, should not exceed 40 mg/day.
    Atropine; Hyoscyamine; Phenobarbital; Scopolamine: (Major) Avoid the use of mifepristone and potent CYP3A inducers such as phenobarbital. It is not known if lowered mifepristone serum levels would lead to reduced response or therapeutic failure. If use together is medically necessary, monitor the patient closely to ensure the proper therapeutic response is obtained.
    Avanafil: (Major) Avoid use of these drugs together. Avanafil for erectile dysfunction is not recommended for use in patients taking strong CYP3A4 inhibitors, Coadministration will lead to increased serum concentrations of avanafil. Mifepristone is a strong CYP3A4 inhibitor. Due to the slow elimination of mifepristone from the body, such interactions may be observed for a prolonged period after mifepristone administration. Use together is likely to result in an increased risk for serious symptomatic hypotension (e.g., dizziness, lightheadedness, fainting).
    Avapritinib: (Major) Avoid coadministration of avapritinib with mifepristone due to the risk of increased avapritinib-related adverse reactions. Avapritinib is a CYP3A4 substrate and mifepristone is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor is predicted to increase the AUC of avapritinib by 600% at steady-state. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
    Avatrombopag: (Major) In patients with chronic immune thrombocytopenia (ITP), reduce the starting dose of avatrombopag to 20 mg PO 3 times weekly when used concomitantly with mifepristone. In patients starting mifepristone while receiving avatrombopag, monitor platelet counts and adjust the avatrombopag dose as necessary. Dosage adjustments are not required for patients with chronic liver disease. Avatrombopag is a CYP2C9 and CYP3A4 substrate, and dual moderate or strong inhibitors such as mifepristone increase avatrombopag exposure, increasing the risk of avatrombopag toxicity.
    Axitinib: (Major) Avoid coadministration of axitinib with mifepristone due to the risk of increased axitinib-related adverse reactions. If coadministration is unavoidable, decrease the dose of axitinib by approximately half; subsequent doses can be increased or decreased based on individual safety and tolerability. Resume the original dose of axitinib approximately 3 to 5 half-lives after mifepristone is discontinued. Axitinib is a CYP3A4/5 substrate and mifepristone is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4/5 inhibitor significantly increased the plasma exposure of axitinib in healthy volunteers. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
    Azithromycin: (Major) Avoid coadministration of azithromycin with mifepristone due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Mifepristone has been associated with dose-dependent prolongation of the QT interval.
    Bedaquiline: (Major) Concurrent use of bedaquiline and a strong CYP3A4 inhibitor, such as mifepristone, for more than 14 days should be avoided unless the benefits justify the risks. Mifepristone may inhibit the metabolism of bedaquiline resulting in increased systemic exposure (AUC) and increased risk for adverse reactions. The activity of mifepristone on CYP3A4 inhibition may be prolonged due to its long half-life, particularly with chronic therapy. Furthermore, since both drugs are associated with QT prolongation, coadministration may result in additive effects on the QT interval. To minimize the risk of QT prolongation, the lowest effective dose of mifepristone should always be used. Prior to initiating bedaquiline, obtain serum electrolyte concentrations and a baseline ECG. An ECG should also be performed at least 2, 12, and 24 weeks after starting bedaquiline therapy.
    Belladonna Alkaloids; Ergotamine; Phenobarbital: (Contraindicated) Use of ergotamine with mifepristone is contraindicated when mifepristone is used chronically for hormonal conditions, such as in the treatment of Cushing's syndrome. Mifepristone, a CYP3A4 inhibitor, is likely to increase ergot alkaloid concentrations and adverse effects, since ergotamine is a CYP3A4 substrate with a narrow therapeutic index. Due to the slow elimination of mifepristone from the body, such interactions may be observed for a prolonged period after mifepristone administration. (Major) Avoid the use of mifepristone and potent CYP3A inducers such as phenobarbital. It is not known if lowered mifepristone serum levels would lead to reduced response or therapeutic failure. If use together is medically necessary, monitor the patient closely to ensure the proper therapeutic response is obtained.
    Benzhydrocodone; Acetaminophen: (Major) Concurrent use of benzhydrocodone with chronic use of mifepristone for Cushing's syndrome may increase the risk of increased opioid-related adverse reactions, such as fatal respiratory depression. Consider alternative therapy. If benzhydrocodone is used, administer the lowest possible dose and/or a decrease the dosing frequency. Monitor patients for respiratory depression and sedation at frequent intervals. Discontinuation of mifepristone in a patient taking benzhydrocodone may decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to opioid agonists. If mifepristone is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Benzhydrocodone is a prodrug for hydrocodone. Hydrocodone is a substrate for CYP3A4. Mifepristone is a strong inhibitor of CYP3A4. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
    Berotralstat: (Major) Reduce the berotralstat dose to 110 mg PO once daily in patients chronically taking mifepristone. Concurrent use may increase berotralstat exposure and the risk of adverse effects. Berotralstat is a P-gp substrate and mifepristone is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased berotralstat exposure by 69%.
    Betrixaban: (Major) Avoid betrixaban use in patients with severe renal impairment receiving mifepristone. Reduce betrixaban dosage to 80 mg PO once followed by 40 mg PO once daily in all other patients receiving mifepristone. Bleeding risk may be increased; monitor patients closely for signs and symptoms of bleeding. Betrixaban is a substrate of P-gp; mifepristone inhibits P-gp.
    Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Major) Concomitant use of metronidazole and mifepristone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Bismuth Subsalicylate; Metronidazole; Tetracycline: (Major) Concomitant use of metronidazole and mifepristone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Boceprevir: (Major) Medications that are potent CYP3A inhibitors, such as boceprevir, are expected to increase plasma mifepristone concentrations. A dose reduction of the current dose of mifepristone may be required when mifepristone is used chronically to treat hormonal conditions, such as Cushing's disease. Adjust to clinical response. Limit the maximum dose of mifepristone to 600 mg/day PO. In a patient already receiving boceprevir, initiate mifepristone at a dose of 300 mg and titrate to a maximum of 600 mg/day if clinically indicated. If therapy with boceprevir is initiated in a patient already receiving mifepristone 300 mg, dosage adjustments are not required. If therapy with boceprevir is initiated in a patient already receiving mifepristone 600 mg, reduce dose of mifepristone to 300 mg/day and titrate to a maximum of 600 mg/day if clinically indicated. If therapy with boceprevir is initiated in a patient already receiving mifepristone 900 mg or 1200 mg, reduce the mifepristone dose to 600 mg/day. Also, CYP3A inhibitors like mifepristone may increase plasma concentrations of boceprevir. Monitor for boceprevir-related adverse effects due to increased boceprevir concentrations. Due to the slow elimination of mifepristone from the body, interactions that occur may be prolonged.
    Bortezomib: (Moderate) Bortezomib is partially metabolized by CYP3A4; mifepristone is a strong CYP3A4 inhibitor. Consider a bortezomib dose reduction if bortezomib is administered with a strong CYP3A4 inhibitor like mifepristone. The effects of mifepristone on drug metabolism may be prolonged due to its long half-life.
    Bosentan: (Major) The use of mifepristone with bosentan is not recommended. Use of a strong CYP3A4 inhibitor like mifepristone will likely lead to large increases in bosentan plasma concentrations. Due to the slow elimination of mifepristone from the body, such interactions may be observed for a prolonged period after mifepristone administration. Bosentan may also induce mifepristone metabolism via CYP3A4. Avoid the use of mifepristone and potent CYP3A inducers due to the potential for reduced mifepristone exposure and reduced efficacy.
    Brexpiprazole: (Moderate) Because brexpiprazole is primarily metabolized by CYP3A4 and CYP2D6, the manufacturer recommends that the brexpiprazole dose be reduced to one-quarter (25%) of the usual dose in patients receiving a moderate to strong inhibitor of CYP3A4 in combination with a moderate to strong inhibitor of CYP2D6. Mifepristone is a moderate inhibitor of CYP3A4 in vitro. If mifepristone is used in combination with brexpiprazole and a moderate to strong CYP2D6 inhibitor, reduce the brexpiprazole dose and carefully monitor the patient for brexpiprazole-related adverse reactions. A reduction of the brexpiprazole dose to 25% of the usual dose is also recommended in patients who are poor metabolizers of CYP2D6 and are receiving a moderate CYP3A4 inhibitor.
    Brigatinib: (Major) Avoid coadministration of brigatinib with mifepristone if possible due to increased plasma exposure of brigatinib; an increase in brigatinib-related adverse reactions may occur. If concomitant use is unavoidable, reduce the dose of brigatinib by approximately 50% without breaking tablets (i.e., from 180 mg to 90 mg; from 90 mg to 60 mg); after discontinuation of mifepristone, resume the brigatinib dose that was tolerated prior to initiation of mifepristone. Brigatinib is a CYP3A4 substrate; mifepristone is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the AUC and Cmax of brigatinib by 101% and 21%, respectively.
    Bromocriptine: (Major) Concomitant use of strong CYP3A4 inhibitors like mifepristone should be avoided when bromocriptine is used for diabetes, and likely when used for other indications. Consider alternative treatments. Concurrent use may increase bromocriptine concentrations substantially, and increase the risk for side effects. Side effects associated with increased blood levels of bromocriptine include nausea, vomiting, constipation, diaphoresis, dizziness, pallor, severe hypotension, confusion, lethargy, drowsiness, and delusions or hallucinations. Bromocriptine is extensively metabolized in the liver via CYP3A4; mifepristone is a strong inhibitor of CYP3A4. Administration of bromocriptine with a moderate inhibitor of CYP3A4 increased the bromocriptine mean AUC and Cmax by 3.7-fold and 4.6-fold, respectively. The prolonged action and long half-life of mifepristone may result in prolonged inhibition of CYP3A4.
    Brompheniramine; Guaifenesin; Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if chronic, concurrent use of mifepristone is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like mifepristone can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If mifepristone is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
    Brompheniramine; Hydrocodone; Pseudoephedrine: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if chronic, concurrent use of mifepristone is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like mifepristone can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If mifepristone is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
    Bupivacaine; Meloxicam: (Moderate) Mifepristone significantly increased exposure of drugs metabolized by CYP2C8/2C9 in interaction studies. Therefore, when mifepristone is used chronically, as in the treatment of Cushing's syndrome, use caution with coadministered CYP2C8/2C9 substrates, including the NSAIDs. Use the lowest doses of the substrate and patients should be monitored closely for adverse reactions.
    Buprenorphine: (Major) Due to the potential for QT prolongation, cautious use and close monitoring are advisable if concurrent use of mifepristone and buprenorphine is necessary. Buprenorphine has been associated with QT prolongation and has a possible risk of torsade de pointes (TdP). Mifepristone also has a possible risk for QT prolongation and TdP. FDA-approved labeling for some buprenorphine products recommend avoiding use with Class 1A and Class III antiarrhythmic medications while other labels recommend avoiding use with any drug that has the potential to prolong the QT interval. Also, the metabolism of buprenorphine is mediated by CYP3A4, and co-administration of a strong CYP3A4 inhibitor such as mifepristone will likely increase buprenorphine levels and cause prolonged or increased opioid effects. If co-administration is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider dose adjustments until stable drug effects are achieved. The effect of CYP3A4 inhibitors on buprenorphine implants has not been studied, and the effect may be dependent on the route of administration.
    Buprenorphine; Naloxone: (Major) Due to the potential for QT prolongation, cautious use and close monitoring are advisable if concurrent use of mifepristone and buprenorphine is necessary. Buprenorphine has been associated with QT prolongation and has a possible risk of torsade de pointes (TdP). Mifepristone also has a possible risk for QT prolongation and TdP. FDA-approved labeling for some buprenorphine products recommend avoiding use with Class 1A and Class III antiarrhythmic medications while other labels recommend avoiding use with any drug that has the potential to prolong the QT interval. Also, the metabolism of buprenorphine is mediated by CYP3A4, and co-administration of a strong CYP3A4 inhibitor such as mifepristone will likely increase buprenorphine levels and cause prolonged or increased opioid effects. If co-administration is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider dose adjustments until stable drug effects are achieved. The effect of CYP3A4 inhibitors on buprenorphine implants has not been studied, and the effect may be dependent on the route of administration.
    Bupropion: (Moderate) Use mifepristone with caution with bupropion. Mifepristone, when used chronically for hormonal conditions such as Cushing's syndrome, is an inhibitor of CYP2B6 and may cause significant increases in exposure of drugs that are metabolized by CYP2B6, such as bupropion. The risk for bupropion-induced adverse reactions, including nausea, dry mouth, restlessness or difficulty with sleep, seizures, hypertension, or neuropsychiatric effects may be increased. Based on clinical response, dosage adjustment of bupropion may be necessary when coadministered with CYP2B6 inhibitors like mifepristone. Due to the slow elimination of mifepristone from the body, any drug interactions that occur may be prolonged.
    Bupropion; Naltrexone: (Moderate) Use mifepristone with caution with bupropion. Mifepristone, when used chronically for hormonal conditions such as Cushing's syndrome, is an inhibitor of CYP2B6 and may cause significant increases in exposure of drugs that are metabolized by CYP2B6, such as bupropion. The risk for bupropion-induced adverse reactions, including nausea, dry mouth, restlessness or difficulty with sleep, seizures, hypertension, or neuropsychiatric effects may be increased. Based on clinical response, dosage adjustment of bupropion may be necessary when coadministered with CYP2B6 inhibitors like mifepristone. Due to the slow elimination of mifepristone from the body, any drug interactions that occur may be prolonged.
    Buspirone: (Moderate) Strong CYP3A4 inhibitors, such as mifepristone, may decrease systemic clearance of buspirone leading to increased concentrations or prolonged effects. If buspirone is to be administered concurrently with significant CYP3A4 inhibitors, a low dose of buspirone (i.e., 2.5 mg PO twice daily) is recommended initially. Subsequent dosage adjustments should be based on clinical response.
    Cabazitaxel: (Major) Avoid coadministration of cabazitaxel with mifepristone if possible due to increased cabazitaxel exposure. If concomitant use is unavoidable, consider reducing the dose of cabazitaxel by 25%. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown. Cabazitaxel is primarily metabolized by CYP3A4 and mifepristone is a strong CYP3A4 inhibitor. In a drug interaction study, coadministration with another strong CYP3A4 inhibitor increased cabazitaxel exposure by 25%.
    Cabotegravir; Rilpivirine: (Major) Avoid use together if possible due to the risk of elevated rilpivirine exposure and a combined risk for QT prolongation. Consider alternatives to rilpivirine when coadministered with a drug with a known risk of QT prolongation and torsade de pointes (TdP), such as mifepristone when it is used for chronic hormonal conditions, such as Cushing's syndrome. Mifepristone is an inhibitor of CYP3A4; rilpivirine is a CYP3A4 substrate. Coadministration is likely to increase rilpivirine plasma concentrations. Monitor for rilpivirine-related side effects, including rash, mood changes or depression, fast, irregular heart rate, and hepatotoxicity. To minimize the risk of QT prolongation, the lowest effect dose of mifepristone should always be used.
    Cabozantinib: (Major) Avoid coadministration of cabozantinib with mifepristone due to the risk of increased cabozantinib exposure; the clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown. If concomitant use is unavoidable, reduce the dose of cabozantinib. For patients taking cabozantinib tablets, reduce the dose of cabozantinib by 20 mg (e.g., 60 mg/day to 40 mg/day; 40 mg/day to 20 mg/day); for patients taking cabozantinib capsules, reduce the dose of cabozantinib by 40 mg (e.g., 140 mg/day to 100 mg/day or 100 mg/day to 60 mg/day). Resume the cabozantinib dose that was used prior to initiating treatment with mifepristone 2 to 3 days after discontinuation of mifepristone. Cabozantinib is a CYP3A4 substrate and mifepristone is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased single-dose cabozantinib exposure by 38%.
    Caffeine; Ergotamine: (Contraindicated) Use of ergotamine with mifepristone is contraindicated when mifepristone is used chronically for hormonal conditions, such as in the treatment of Cushing's syndrome. Mifepristone, a CYP3A4 inhibitor, is likely to increase ergot alkaloid concentrations and adverse effects, since ergotamine is a CYP3A4 substrate with a narrow therapeutic index. Due to the slow elimination of mifepristone from the body, such interactions may be observed for a prolonged period after mifepristone administration.
    Capmatinib: (Moderate) Monitor for an increase in capmatinib-related adverse reactions if coadministration with mifepristone is necessary. Capmatinib is a CYP3A substrate and mifepristone is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased capmatinib exposure by 42%. The interaction is most likely when mifepristone is used chronically to treat hormonal conditions, such as Cushing's disease. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
    Carbamazepine: (Major) No medications that induce CYP3A4 have been studied when co-administered with mifepristone. Avoid co-administration of chronic mifepristone and potent CYP3A inducers such as carbamazepine. If use together is necessary, use with extreme caution, then base decisions about mifepristone dose increases on a clinical assessment of tolerability and degree of improvement in disease manifestations. Mifepristone is a strong CYP3A4 inhibitor. Carbamazepine is metabolized by CYP3A4 and increased carbamazepine concentrations are expected. The lowest possible dose and/or a decreased frequency of dosing must be used with therapeutic drug monitoring of carbamazepine levels when possible. Consider if an alternative agent is appropriate.
    Carbinoxamine; Hydrocodone; Phenylephrine: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if chronic, concurrent use of mifepristone is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like mifepristone can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If mifepristone is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
    Carbinoxamine; Hydrocodone; Pseudoephedrine: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if chronic, concurrent use of mifepristone is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like mifepristone can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If mifepristone is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
    Cariprazine: (Major) Cariprazine and its active metabolites are extensively metabolized by CYP3A4. Dosage reductions of cariprazine are recommended in patients taking strong CYP3A4 inhibitors, such as mifepristone. If a strong CYP3A4 inhibitor is initiated, reduce the current dosage of cariprazine by half. If the patient is already taking the CYP3A4 inhibitor and initiating cariprazine, an alternative initation regimen for cariprazine is recommended in the prescribing information. Monitoring for adverse effects, such as CNS effects and extrapyramidal symptoms, is advisable during coadministration.
    Celecoxib: (Moderate) Mifepristone significantly increased exposure of drugs metabolized by CYP2C8/2C9 in interaction studies. Therefore, when mifepristone is used chronically, as in the treatment of Cushing's syndrome, use caution with coadministered CYP2C8/2C9 substrates, including the NSAIDs. Use the lowest doses of the substrate and patients should be monitored closely for adverse reactions.
    Ceritinib: (Major) Avoid coadministration of mifepristone with ceritinib due to the risk of additive QT prolongation; the exposure of both drugs may also be increased. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. If concomitant use of mifepristone is necessary for the treatment of Cushing's syndrome in a patient already receiving ceritinib, initiate mifepristone at a dose of 300 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with ceritinib is initiated in a patient already receiving mifepristone 300 mg, dosage adjustments are not required. If therapy with ceritinib is initiated in a patient already receiving mifepristone 600 mg, reduce dose of mifepristone to 300 mg and titrate to a maximum of 600 mg if clinically indicated. If therapy with ceritinib is initiated in a patient already receiving 900 mg, reduce dose of mifepristone to 600 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with ceritinib is initiated in a patient already receiving 1,200 mg, reduce the mifepristone dose to 900 mg. Both mifepristone and ceritinib are substrates and strong inhibitors of CYP3A4 that are associated with QT prolongation.
    Chloramphenicol: (Major) Caution is advised when administering chloramphenicol with mifepristone because increased serum concentrations of either drug may occur. When mifepristone is used in the treatment of Cushing's syndrome, coadministration with chloramphenicol should be done only when necessary, and in such cases the dose of mifepristone should be limited to a maximum dose of 900 mg per day. In a patient already receiving chloramphenicol, initiate mifepristone at a dose of 300 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with chloramphenicol is initiated in a patient already receiving mifepristone 300 mg, dosage adjustments are not required. If therapy with chloramphenicol is initiated in a patient already receiving mifepristone 600 mg, reduce dose of mifepristone to 300 mg and titrate to a maximum of 600 mg if clinically indicated. If therapy with chloramphenicol is initiated in a patient already receiving 900 mg, reduce dose of mifepristone to 600 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with chloramphenicol is initiated in a patient already receiving 1,200 mg, reduce the mifepristone dose to 900 mg. Mifepristone is a CYP3A4 substrate; chloramphenicol is a strong CYP3A4 inhibitor.
    Chloroquine: (Major) Avoid coadministration of chloroquine with mifepristone due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Chloroquine is associated with an increased risk of QT prolongation and torsade de pointes (TdP); the risk of QT prolongation is increased with higher chloroquine doses. Mifepristone is associated with dose-related prolongation of the QT interval.
    Chlorpheniramine; Codeine: (Moderate) Concomitant use of codeine with chronic mifepristone therapy may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of mifepristone could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If mifepristone is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Mifepristone is a strong inhibitor of CYP3A4. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
    Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Concomitant use of dihydrocodeine with chronic mifepristone therapy may increase dihydrocodeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased dihydromorphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of dihydrocodeine until stable drug effects are achieved. Discontinuation of mifepristone could decrease dihydrocodeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to dihydrocodeine. If mifepristone is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Mifepristone is a strong inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
    Chlorpheniramine; Dihydrocodeine; Pseudoephedrine: (Moderate) Concomitant use of dihydrocodeine with chronic mifepristone therapy may increase dihydrocodeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased dihydromorphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of dihydrocodeine until stable drug effects are achieved. Discontinuation of mifepristone could decrease dihydrocodeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to dihydrocodeine. If mifepristone is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Mifepristone is a strong inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
    Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if chronic, concurrent use of mifepristone is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like mifepristone can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If mifepristone is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
    Chlorpheniramine; Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if chronic, concurrent use of mifepristone is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like mifepristone can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If mifepristone is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
    Chlorpheniramine; Hydrocodone; Phenylephrine: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if chronic, concurrent use of mifepristone is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like mifepristone can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If mifepristone is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
    Chlorpheniramine; Hydrocodone; Pseudoephedrine: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if chronic, concurrent use of mifepristone is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like mifepristone can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If mifepristone is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
    Cilostazol: (Moderate) Mifepristone is a strong inhibitor of CYP3A4. Use of mifepristone may lead to an increase in serum levels of drugs that are CYP3A4 substrates, such as cilostazol. Strong CYP3A4 inhibitors have significantly increased the systemic exposure of cilostazol and/or its major metabolites. Due to the slow elimination of mifepristone from the body, such interactions may be observed for a prolonged period after mifepristone administration. If use together is medically necessary, use the lowest dose of cilostazol necessary (e.g., 50 mg PO twice daily), with appropriate monitoring and follow-up. Side effects of cilostazol may include unusual bleeding or bruising, diarrhea, dizziness, edema (such as swelling of the ankles or legs), headache, or upset stomach.
    Ciprofloxacin: (Moderate) Due to a possible risk for QT prolongation and torsade de pointes (TdP), mifepristone and ciprofloxacin should be used together cautiously. Mifepristone has been associated with dose-dependent prolongation of the QT interval. There is no experience with high exposure or concomitant use with other QT prolonging drugs. To minimize the risk of QT prolongation, the lowest effective dose should always be used. Rare cases of QT prolongation and TdP have been reported with ciprofloxacin during postmarketing surveillance. Ciprofloxacin should be used with caution in patients receiving other drugs that might prolong the QT interval.
    Cisapride: (Contraindicated) QT prolongation and ventricular arrhythmias, including torsade de pointes (TdP) and death, have been reported with cisapride. Because of the potential for TdP, use of other drugs with a potential for QT prolongation along with cisapride is contraindicated. Mifepristone has been associated with a risk for QT prolongation.
    Citalopram: (Major) Avoid use of these drugs together if possible; consider alternative therapies. Citalopram causes dose-dependent QT interval prolongation.The concurrent use of citalopram with other drugs that prolong the QT interval is not recommended. If concurrent therapy is considered essential, ECG monitoring is recommended. Mifepristone, when used chronically for hormonal conditions like Cushing's syndrome, has been associated with dose-dependent prolongation of the QT interval. To minimize the risk of QT prolongation, the lowest effective dose of mifepristone should always be used.
    Clarithromycin: (Major) Avoid coadministration of mifepristone with clarithromycin due to the risk of additive QT prolongation and torsade de pointes (TdP); the exposure of both drugs may also be increased. If concomitant use of mifepristone is necessary for the treatment of Cushing's syndrome in a patient already receiving clarithromycin, initiate mifepristone at a dose of 300 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with clarithromycin is initiated in a patient already receiving mifepristone 300 mg, dosage adjustments are not required. If therapy with clarithromycin is initiated in a patient already receiving mifepristone 600 mg, reduce dose of mifepristone to 300 mg and titrate to a maximum of 600 mg if clinically indicated. If therapy with clarithromycin is initiated in a patient already receiving 900 mg, reduce dose of mifepristone to 600 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with clarithromycin is initiated in a patient already receiving 1,200 mg, reduce the mifepristone dose to 900 mg. Both mifepristone and clarithromycin are substrates and strong inhibitors of CYP3A4 that are associated with QT prolongation.
    Clindamycin: (Moderate) Monitor for an increase in clindamycin-related adverse reactions with coadministration of mifepristone as concurrent use may increase clindamycin exposure. Clindamycin is a CYP3A4 substrate; mifepristone is a strong inhibitor of CYP3A4.
    Clofazimine: (Major) Monitor ECG and use the lowest effective dose of mifepristone if clofazimine is coadministered due to the potential for additive QT prolongation. QT prolongation and torsade de pointes have been reported in patients receiving clofazimine in combination with QT prolonging medications. Mifepristone has been associated with dose-dependent prolongation of the QT interval.
    Clomipramine: (Minor) Due to a possible risk for QT prolongation and torsade de pointes (TdP), mifepristone and tricyclic antidepressants should be used together cautiously. Mifepristone has been associated with dose-dependent prolongation of the QT interval. There is no experience with high exposure or concomitant use with other QT prolonging drugs. To minimize the risk of QT prolongation, the lowest effective dose should always be used. Drugs with a possible risk for QT prolongation and torsades de pointes that should be used cautiously with mifepristone include tricyclic antidepressants.
    Clonazepam: (Moderate) Use mifepristone cautiously and carefully monitor patients receiving concurrent clonazepam due to impaired metabolism of clonazepam leading to exaggerated concentrations and adverse effects, such as CNS and/or respiratory depression. Clonazepam is a CYP3A4 substrate. Mifepristone is a CYP3A4 inhibitor.
    Clozapine: (Moderate) Avoid use together when possible. Use extreme caution when administering concomitant medications that prolong the QT interval or inhibit the metabolism of clozapine, such as mifepristone, which may do both. Treatment with clozapine has been associated with QT prolongation, torsade de pointes (TdP), cardiac arrest, and sudden death. Mifepristone has also been associated with QT prolongation. Mifepristone is an inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of clozapine. Elevated plasma concentrations of clozapine occurring through inhibition of CYP3A4 may potentially increase the risk of life-threatening arrhythmias or other clozapine-related adverse effects such as sedation, anticholinergic effects, seizures, orthostasis, or other adverse effects. According to the manufacturer, patients receiving clozapine in combination with a CYP3A4 inhibitor should be monitored for adverse reactions. Consideration should be given to reducing the clozapine dose if necessary. If the inhibitor is discontinued, monitor for lack of clozapine effectiveness and consider increasing the clozapine dose if necessary.
    Cobicistat: (Major) Caution is advised when administering cobicistat with mifepristone because increased serum concentrations of either drug may occur. When mifepristone is used in the treatment of Cushing's syndrome, coadministration with cobicistat should be done only when necessary, and in such cases the dose of mifepristone should be limited to a maximum dose of 900 mg per day. In a patient already receiving cobicistat, initiate mifepristone at a dose of 300 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with cobicistat is initiated in a patient already receiving mifepristone 300 mg, dosage adjustments are not required. If therapy with cobicistat is initiated in a patient already receiving mifepristone 600 mg, reduce dose of mifepristone to 300 mg and titrate to a maximum of 600 mg if clinically indicated. If therapy with cobicistat is initiated in a patient already receiving 900 mg, reduce dose of mifepristone to 600 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with cobicistat is initiated in a patient already receiving 1,200 mg, reduce the mifepristone dose to 900 mg. Both mifepristone and cobicistat are substrates and strong inhibitors of CYP3A4.
    Cobimetinib: (Major) Avoid the concurrent use of cobimetinib with chronic mifepristone therapy due to the risk of cobimetinib toxicity. If concurrent short-term (14 days or less) use of mifepristone is unavoidable, reduce the dose of cobimetinib to 20 mg once daily for patients normally taking 60 mg daily; after discontinuation of mifepristone, resume cobimetinib at the previous dose. Use an alternative to mifepristone in patients who are already taking a reduced dose of cobimetinib (40 or 20 mg daily). Cobimetinib is a P-glycoprotein (P-gp) substrate as well as a CYP3A substrate in vitro; mifepristone is a strong inhibitor of CYP3A as well as a P-gp inhibitor.
    Codeine: (Moderate) Concomitant use of codeine with chronic mifepristone therapy may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of mifepristone could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If mifepristone is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Mifepristone is a strong inhibitor of CYP3A4. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
    Codeine; Guaifenesin: (Moderate) Concomitant use of codeine with chronic mifepristone therapy may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of mifepristone could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If mifepristone is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Mifepristone is a strong inhibitor of CYP3A4. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
    Codeine; Phenylephrine; Promethazine: (Moderate) Concomitant use of codeine with chronic mifepristone therapy may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of mifepristone could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If mifepristone is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Mifepristone is a strong inhibitor of CYP3A4. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown. (Moderate) Promethazine carries a possible risk of QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with promethazine include mifepristone.
    Codeine; Promethazine: (Moderate) Concomitant use of codeine with chronic mifepristone therapy may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of mifepristone could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If mifepristone is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Mifepristone is a strong inhibitor of CYP3A4. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown. (Moderate) Promethazine carries a possible risk of QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with promethazine include mifepristone.
    Colchicine: (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and mifepristone in patients with normal renal and hepatic function unless the use of both agents is imperative. Coadministration is contraindicated in patients with renal or hepatic impairment because colchicine accumulation may be greater in these populations. Mifepristone can inhibit colchicine's metabolism via P-glycoprotein (P-gp) and CYP3A4, resulting in increased colchicine exposure. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken a moderate CYP3A4 inhibitor like mifepristone in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg twice daily or 0.6 mg once daily or if the original dose is 0.6 mg once daily, decrease the dose to 0.3 mg once daily; for treatment of gout flares, give 1.2 mg as a single dose and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed 1.2 mg/day.
    Colchicine; Probenecid: (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and mifepristone in patients with normal renal and hepatic function unless the use of both agents is imperative. Coadministration is contraindicated in patients with renal or hepatic impairment because colchicine accumulation may be greater in these populations. Mifepristone can inhibit colchicine's metabolism via P-glycoprotein (P-gp) and CYP3A4, resulting in increased colchicine exposure. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken a moderate CYP3A4 inhibitor like mifepristone in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg twice daily or 0.6 mg once daily or if the original dose is 0.6 mg once daily, decrease the dose to 0.3 mg once daily; for treatment of gout flares, give 1.2 mg as a single dose and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed 1.2 mg/day.
    Conivaptan: (Contraindicated) Coadministration of conivaptan and mifepristone is contraindicated due to the potential for increased conivaptan exposure; mifepristone exposure may also be increased. Subsequent treatment with mifepristone should be initiated no sooner than 1 week after the infusion of conivaptan is completed. If concomitant use of mifepristone is necessary for the treatment of Cushing's syndrome in a patient already receiving conivaptan, initiate mifepristone at a dose of 300 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with conivaptan is initiated in a patient already receiving mifepristone 300 mg, dosage adjustments are not required. If therapy with conivaptan is initiated in a patient already receiving mifepristone 600 mg, reduce dose of mifepristone to 300 mg and titrate to a maximum of 600 mg if clinically indicated. If therapy with conivaptan is initiated in a patient already receiving 900 mg, reduce dose of mifepristone to 600 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with conivaptan is initiated in a patient already receiving 1,200 mg, reduce the mifepristone dose to 900 mg. Both mifepristone and conivaptan are substrates and strong inhibitors of CYP3A4.
    Conjugated Estrogens: (Minor) Estrogens are partially metabolized by CYP3A4. Drugs that inhibit CYP3A4 such as mifepristone may increase plasma concentrations of estrogens and cause estrogen-related side effects such as nausea and breast tenderness. Patients receiving estrogens should be monitored for an increase in adverse events.
    Conjugated Estrogens; Bazedoxifene: (Minor) Estrogens are partially metabolized by CYP3A4. Drugs that inhibit CYP3A4 such as mifepristone may increase plasma concentrations of estrogens and cause estrogen-related side effects such as nausea and breast tenderness. Patients receiving estrogens should be monitored for an increase in adverse events.
    Conjugated Estrogens; Medroxyprogesterone: (Minor) Estrogens are partially metabolized by CYP3A4. Drugs that inhibit CYP3A4 such as mifepristone may increase plasma concentrations of estrogens and cause estrogen-related side effects such as nausea and breast tenderness. Patients receiving estrogens should be monitored for an increase in adverse events.
    Corticosteroids: (Major) Mifepristone for termination of pregnancy is contraindicated in patients on long-term corticosteroid therapy and mifepristone for Cushing's disease or other chronic conditions is contraindicated in patients who require concomitant treatment with systemic corticosteroids for life-saving purposes, such as serious medical conditions or illnesses (e.g., immunosuppression after organ transplantation). For other situations where corticosteroids are used for treating non-life threatening conditions, mifepristone may lead to reduced corticosteroid efficacy and exacerbation or deterioration of such conditions. This is because mifepristone exhibits antiglucocorticoid activity that may antagonize corticosteroid therapy and the stabilization of the underlying corticosteroid-treated illness. Mifepristone may also cause adrenal insufficiency, so patients receiving corticosteroids for non life-threatening illness require close monitoring. Because serum cortisol levels remain elevated and may even increase during treatment with mifepristone, serum cortisol levels do not provide an accurate assessment of hypoadrenalism. Patients should be closely monitored for signs and symptoms of adrenal insufficiency, If adrenal insufficiency occurs, stop mifepristone treatment and administer systemic glucocorticoids without delay; high doses may be needed to treat these events. Factors considered in deciding on the duration of glucocorticoid treatment should include the long half-life of mifepristone (85 hours).
    Crizotinib: (Major) Avoid concomitant use of mifepristone and crizotinib due to increased plasma concentrations of crizotinib, which may increase the incidence and severity of adverse reactions; QT prolonation may also occur. If concomitant use is necessary, always use the lowest effective dose of mifepristone. Reduce the dose of crizotinib to 250 mg PO once daily for patients with non-small cell lung cancer. If concomitant use is necessary for patients with anaplastic large cell lymphoma, reduce the dose of crizotinib to 250 mg PO twice daily for BSA of 1.7 m2 or more; 200 mg PO twice daily for BSA of 1.17 to 1.69 m2; and 250 mg PO once daily for BSA of 0.81 to 1.16 m2; do not use this combination in patients with a BSA of 0.6 to 0.8 m2. Monitor ECGs for QT prolongation and monitor electrolytes; an interruption of therapy, dose reduction, or discontinuation of therapy may be necessary for crizotinib if QT prolongation occurs. Resume the original crizotinib dose after discontinuation of mifepristone. Crizotinib is a CYP3A substrate that has been associated with concentration-dependent QT prolongation. Mifepristone is a strong CYP3A4 inhibitor that has also been associated with dose-dependent prolongation of the QT interval. Coadministration with one strong CYP3A inhibitor increased the AUC of single-dose crizotinib by 216%. Concomitant use with another strong CYP3A4 inhibitor increased the steady-state AUC of crizotinib by 57% compared to crizotinib alone.
    Cyclosporine: (Contraindicated) Coadministration of cyclosporine is contraindicated when mifepristone is used chronically, such as in the treatment of Cushing's syndrome. Mifepristone, a CYP3A4 inhibitor, is likely to increase cyclosporine concentrations and adverse effects, since cyclosporine is a CYP3A4 substrate with a narrow therapeutic index. Due to the slow elimination of mifepristone from the body, such interactions may be observed for a prolonged period after mifepristone administration.
    Dabigatran: (Major) When mifepristone is used for the termination of pregnancy, concurrent use of anticoagulants is contraindicated due to the increased risk of serious bleeding. It is not clear if mifepristone exhibits a pharmacokinetic interaction with dabigatran. Use together with caution when mifepristone is given chronically for other conditions, such as Cushing's syndrome. Increased serum concentrations of dabigatran might be possible as mifepristone may be an inhibitor of P-gp. Patients should be monitored for bleeding and increased adverse effects of dabigatran. P-gp inhibition and renal impairment are the major independent factors that result in increased exposure to dabigatran. Different recommendations may apply to the use of mifepristone with dabigatran when the patient is also renally impaired. Due to the slow eilimination of mifepristone, any interaction that does occur may be prolonged.
    Daclatasvir: (Moderate) Administration of daclatasvir with mifepristone may increase daclatasvir serum concentrations. If these drugs are coadministered, monitor patients for daclatasvir-related adverse effects, such as headache, fatigue, nausea, and diarrhea. Daclatasvir is a CYP3A4 and P-gp substrate, and mifepristone is a known CYP3A4 inhibitor and possibly a P-gp inhibitor. Due to the slow elimination of mifepristone from the body, such interactions may be observed for a prolonged period after mifepristone administration.
    Dalteparin: (Major) When mifepristone is used for the termination of pregnancy, concurrent use of anticoagulants is contraindicated due to the increased risk of serious bleeding. Consider an alternative to mifepristone in these circumstances. When mifepristone is used chronically for other conditions, such as Cushing's disease, an interaction with low-molecular weight heparins is not expected; however, follow usual cautions and monitor as per standard of care.
    Dapagliflozin; Saxagliptin: (Moderate) Monitor patients for hypoglycemia if saxagliptin and mifepristone are used together; dosage reduction of saxagliptin may be needed in some patients. In patients taking CYP3A substrates, the manufacturer of mifepristone recommends that the lowest dose of the CYP3A substrate that achieves the proper clinical response and tolerability be used. When potent CYP3A inhibitors are used, the initial dose of saxagliptin should be limited to 2.5 mg/day; mifepristone is a CYP3A inhibitor and has been noted to increase concentrations of CYP3A substrates. Due to the slow elimination of mifepristone from the body, such interactions may be observed for a prolonged period after mifepristone administration.
    Darifenacin: (Moderate) The daily dose of darifenacin should not exceed 7.5 mg/day PO in adults receiving mifepristone chronically for the treatment of hormonal conditions. The exposure of darifenacin, a sensitive CYP3A4 substrate, is expected to increase significantly with the administration of mifepristone when mifepristone is used chronically for hormonal conditions, such as Cushing's syndrome. Mifepristone is a CYP3A4 inhibitor. Due to the slow elimination of mifepristone from the body, any drug interactions that occur may be prolonged.
    Darolutamide: (Moderate) Monitor patients more frequently for darolutamide-related adverse reactions if coadministration with mifepristone is necessary due to the risk of increased darolutamide exposure; decrease the dose of darolutamide for grade 3 or 4 adverse reactions or for otherwise intolerable adverse reactions. Mifepristone is a P-glycoprotein (P-gp) inhibitor and a strong CYP3A4 inhibitor; darolutamide is a CYP3A4 substrate. Concomitant use with another combined P-gp inhibitor and strong CYP3A4 inhibitor increased the mean AUC and Cmax of darolutamide by 1.7-fold and 1.4-fold, respectively.
    Darunavir: (Major) Caution is advised when administering darunavir with mifepristone because increased serum concentrations of either drug may occur. When mifepristone is used in the treatment of Cushing's syndrome, coadministration with darunavir should be done only when necessary, and in such cases the dose of mifepristone should be limited to a maximum dose of 900 mg per day. In a patient already receiving darunavir, initiate mifepristone at a dose of 300 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with darunavir is initiated in a patient already receiving mifepristone 300 mg, dosage adjustments are not required. If therapy with darunavir is initiated in a patient already receiving mifepristone 600 mg, reduce dose of mifepristone to 300 mg and titrate to a maximum of 600 mg if clinically indicated. If therapy with darunavir is initiated in a patient already receiving 900 mg, reduce dose of mifepristone to 600 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with darunavir is initiated in a patient already receiving 1,200 mg, reduce the mifepristone dose to 900 mg. Both mifepristone and darunavir are substrates and strong inhibitors of CYP3A4.
    Darunavir; Cobicistat: (Major) Caution is advised when administering cobicistat with mifepristone because increased serum concentrations of either drug may occur. When mifepristone is used in the treatment of Cushing's syndrome, coadministration with cobicistat should be done only when necessary, and in such cases the dose of mifepristone should be limited to a maximum dose of 900 mg per day. In a patient already receiving cobicistat, initiate mifepristone at a dose of 300 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with cobicistat is initiated in a patient already receiving mifepristone 300 mg, dosage adjustments are not required. If therapy with cobicistat is initiated in a patient already receiving mifepristone 600 mg, reduce dose of mifepristone to 300 mg and titrate to a maximum of 600 mg if clinically indicated. If therapy with cobicistat is initiated in a patient already receiving 900 mg, reduce dose of mifepristone to 600 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with cobicistat is initiated in a patient already receiving 1,200 mg, reduce the mifepristone dose to 900 mg. Both mifepristone and cobicistat are substrates and strong inhibitors of CYP3A4. (Major) Caution is advised when administering darunavir with mifepristone because increased serum concentrations of either drug may occur. When mifepristone is used in the treatment of Cushing's syndrome, coadministration with darunavir should be done only when necessary, and in such cases the dose of mifepristone should be limited to a maximum dose of 900 mg per day. In a patient already receiving darunavir, initiate mifepristone at a dose of 300 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with darunavir is initiated in a patient already receiving mifepristone 300 mg, dosage adjustments are not required. If therapy with darunavir is initiated in a patient already receiving mifepristone 600 mg, reduce dose of mifepristone to 300 mg and titrate to a maximum of 600 mg if clinically indicated. If therapy with darunavir is initiated in a patient already receiving 900 mg, reduce dose of mifepristone to 600 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with darunavir is initiated in a patient already receiving 1,200 mg, reduce the mifepristone dose to 900 mg. Both mifepristone and darunavir are substrates and strong inhibitors of CYP3A4.
    Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) Caution is advised when administering cobicistat with mifepristone because increased serum concentrations of either drug may occur. When mifepristone is used in the treatment of Cushing's syndrome, coadministration with cobicistat should be done only when necessary, and in such cases the dose of mifepristone should be limited to a maximum dose of 900 mg per day. In a patient already receiving cobicistat, initiate mifepristone at a dose of 300 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with cobicistat is initiated in a patient already receiving mifepristone 300 mg, dosage adjustments are not required. If therapy with cobicistat is initiated in a patient already receiving mifepristone 600 mg, reduce dose of mifepristone to 300 mg and titrate to a maximum of 600 mg if clinically indicated. If therapy with cobicistat is initiated in a patient already receiving 900 mg, reduce dose of mifepristone to 600 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with cobicistat is initiated in a patient already receiving 1,200 mg, reduce the mifepristone dose to 900 mg. Both mifepristone and cobicistat are substrates and strong inhibitors of CYP3A4. (Major) Caution is advised when administering darunavir with mifepristone because increased serum concentrations of either drug may occur. When mifepristone is used in the treatment of Cushing's syndrome, coadministration with darunavir should be done only when necessary, and in such cases the dose of mifepristone should be limited to a maximum dose of 900 mg per day. In a patient already receiving darunavir, initiate mifepristone at a dose of 300 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with darunavir is initiated in a patient already receiving mifepristone 300 mg, dosage adjustments are not required. If therapy with darunavir is initiated in a patient already receiving mifepristone 600 mg, reduce dose of mifepristone to 300 mg and titrate to a maximum of 600 mg if clinically indicated. If therapy with darunavir is initiated in a patient already receiving 900 mg, reduce dose of mifepristone to 600 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with darunavir is initiated in a patient already receiving 1,200 mg, reduce the mifepristone dose to 900 mg. Both mifepristone and darunavir are substrates and strong inhibitors of CYP3A4.
    Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Major) Caution is advised when administering ritonavir with mifepristone because increased serum concentrations of either drug may occur. When mifepristone is used in the treatment of Cushing's syndrome, coadministration with ritonavir should be done only when necessary, and in such cases the dose of mifepristone should be limited to a maximum dose of 900 mg per day. In a patient already receiving ritonavir, initiate mifepristone at a dose of 300 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with ritonavir is initiated in a patient already receiving mifepristone 300 mg, dosage adjustments are not required. If therapy with ritonavir is initiated in a patient already receiving mifepristone 600 mg, reduce dose of mifepristone to 300 mg and titrate to a maximum of 600 mg if clinically indicated. If therapy with ritonavir is initiated in a patient already receiving 900 mg, reduce dose of mifepristone to 600 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with ritonavir is initiated in a patient already receiving 1,200 mg, reduce the mifepristone dose to 900 mg. Both mifepristone and ritonavir are substrates and strong inhibitors of CYP3A4. (Major) Elevated ombitasvir concentrations may result if mifepristone is coadministered chronically. If these drugs must be used together, closely monitor the patient for antiviral-related adverse events. Because ombitasvir is used in drug regimens that may reduce the clearance of mifepristone and increase the risk for QT prolongation, dosage reduction of mifepristone is necessary with certain medications. The response to mifepristone, when used chronically for hormonal conditions like Cushing's syndrome, requires careful monitoring. Consult the mifepristone package insert/product labeling for appropriate dose reduction. Mifepristone is a CYP3A4 inhibitor and substrate and may be a P-glycoprotein (P-gp) inhibitor. Ombitasvir is a P-gp substrate. Inhibition of P-gp may increase the plasma concentrations of ombitasvir. (Major) Elevated paritaprevir concentrations may result if mifepristone is coadministered chronically. If these drugs must be used together, closely monitor the patient for antiviral-related adverse events. Because paritaprevir is used in drug regimens that may reduce the clearance of mifepristone and increase the risk for QT prolongation, dosage reduction of mifepristone is necessary with certain medications. The response to mifepristone, when used chronically for hormonal conditions like Cushing's syndrome, requires careful monitoring. Consult the mifepristone package insert/product labeling for appropriate dose reduction. Mifepristone is a CYP3A4 inhibitor and may inhibit P-glycoprotein (P-gp). Paritaprevir is a CYP3A4 and P-gp substrate. (Major) Use is not recommended. Dasabuvir is primarily metabolized by CYP2C8 and mifepristone may significantly inhibit CYP2C8 and may increase dasabuvir plasma concentrations and risk for adverse effects, including QT prolongation. Dasabuvir is primarily metabolized by CYP2C8 enzymes and is contraindicated with drugs that are strong inhibitors of CYP2C8. Consider alternatives to chronic mifepristone therapy in patients receiving dasabuvir. Due to the slow elimination of mifepristone from the body, interactions that occur may be prolonged. If use together cannot be avoided, patients should be closely monitored for dasabuvir-related adverse effects, such as nausea, liver problems, skin rash, trouble sleeping, unusual tiredness or weakness, and QT prolongation.
    Dasatinib: (Major) Avoid coadministration of dasatinib and mifepristone due to the potential for increased dasatinib exposure and subsequent toxicity including QT prolongation and torsade de pointes (TdP). An alternative to mifepristone with no or minimal enzyme inhibition potential is recommended if possible. If coadministration cannot be avoided, consider a dasatinib dose reduction to 40 mg PO daily if original dose was 140 mg daily, 20 mg PO daily if original dose was 100 mg daily, or 20 mg PO daily if original dose was 70 mg daily. Concomitant use of mifepristone is not recommended in patients receiving dasatinib 60 mg or 40 mg daily. If dasatinib is not tolerated after dose reduction, consider alternative therapies. If mifepristone is stopped, allow a washout of approximately 1 week before increasing the dasatinib dose. Dasatinib is a CYP3A4 substrate that has the potential to prolong the QT interval; mifepristone is a strong CYP3A4 inhibitor that is associated with dose-dependent prolongation of the QT interval. Coadministration of another strong CYP3A4 inhibitor increased the mean Cmax and AUC of dasatinib by 4-fold and 5-fold, respectively.
    Degarelix: (Major) Avoid use of mifepristone with QT interval prolonging drugs like degarelix. Mifepristone is associated with dose-related prolongation of the QT interval. Androgen deprivation therapy (i.e., degarelix) may also prolong the QT/QTc interval.
    Delavirdine: (Major) Caution is advised when administering delavirdine with mifepristone because increased serum concentrations of either drug may occur. When mifepristone is used in the treatment of Cushing's syndrome, coadministration with delavirdine should be done only when necessary, and in such cases the dose of mifepristone should be limited to a maximum dose of 900 mg per day. In a patient already receiving delavirdine, initiate mifepristone at a dose of 300 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with delavirdine is initiated in a patient already receiving mifepristone 300 mg, dosage adjustments are not required. If therapy with delavirdine is initiated in a patient already receiving mifepristone 600 mg, reduce dose of mifepristone to 300 mg and titrate to a maximum of 600 mg if clinically indicated. If therapy with delavirdine is initiated in a patient already receiving 900 mg, reduce dose of mifepristone to 600 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with delavirdine is initiated in a patient already receiving 1,200 mg, reduce the mifepristone dose to 900 mg. Both mifepristone and delavirdine are substrates and strong inhibitors of CYP3A4.
    Desflurane: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with mifepristone. Halogenated anesthetics can prolong the QT interval. Mifepristone has been associated with dose-dependent prolongation of the QT interval. There is no experience with high exposure or concomitant use with other QT prolonging drugs. To minimize the risk of QT prolongation, the lowest effective dose should always be used.
    Desipramine: (Minor) Due to a possible risk for QT prolongation and torsade de pointes (TdP), mifepristone and tricyclic antidepressants should be used together cautiously. Mifepristone has been associated with dose-dependent prolongation of the QT interval. There is no experience with high exposure or concomitant use with other QT prolonging drugs. To minimize the risk of QT prolongation, the lowest effective dose should always be used. Drugs with a possible risk for QT prolongation and torsades de pointes that should be used cautiously with mifepristone include tricyclic antidepressants.
    Deutetrabenazine: (Major) Avoid use of mifepristone with QT interval prolonging drugs. Mifepristone is associated with dose-related prolongation of the QT interval. Deutetrabenazine may prolong the QT interval, but the degree of QT prolongation is not clinically significant when deutetrabenazine is administered within the recommended dosage range.
    Dextromethorphan; Quinidine: (Contraindicated) Use of quinidine with mifepristone is contraindicated when mifepristone is used chronically for hormonal conditions, such as in the treatment of Cushing's syndrome. Mifepristone, a CYP3A4 inhibitor, is likely to increase quinidine concentrations and adverse effects, since quinidine is a CYP3A4 substrate with a narrow therapeutic index. Increased quinidine concentrations are likely to cause proarrythmia and ECG changes, as well as symptoms of cinchonism. Both quinidine and mifepristone have been associated with QT prolongation and a risk for torsade de pointes (TdP). Due to the slow elimination of mifepristone from the body, such interactions may be observed for a prolonged period after mifepristone administration.
    Diclofenac: (Moderate) Mifepristone significantly increased exposure of drugs metabolized by CYP2C8/2C9 in interaction studies. Therefore, when mifepristone is used chronically, as in the treatment of Cushing's syndrome, use caution with coadministered CYP2C8/2C9 substrates, including the NSAIDs. Use the lowest doses of the substrate and patients should be monitored closely for adverse reactions.
    Diclofenac; Misoprostol: (Moderate) Mifepristone significantly increased exposure of drugs metabolized by CYP2C8/2C9 in interaction studies. Therefore, when mifepristone is used chronically, as in the treatment of Cushing's syndrome, use caution with coadministered CYP2C8/2C9 substrates, including the NSAIDs. Use the lowest doses of the substrate and patients should be monitored closely for adverse reactions.
    Dienogest; Estradiol valerate: (Contraindicated) Mifepristone is a progesterone-receptor antagonist and will interfere with the effectiveness of hormonal contraceptives. Therefore, non-hormonal contraceptive methods should be used in Cushing's patients taking mifepristone.
    Diflunisal: (Moderate) Mifepristone significantly increased exposure of drugs metabolized by CYP2C8/2C9 in interaction studies. Therefore, when mifepristone is used chronically, as in the treatment of Cushing's syndrome, use caution with coadministered CYP2C8/2C9 substrates, including the NSAIDs. Use the lowest doses of the substrate and patients should be monitored closely for adverse reactions.
    Dihydrocodeine; Guaifenesin; Pseudoephedrine: (Moderate) Concomitant use of dihydrocodeine with chronic mifepristone therapy may increase dihydrocodeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased dihydromorphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of dihydrocodeine until stable drug effects are achieved. Discontinuation of mifepristone could decrease dihydrocodeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to dihydrocodeine. If mifepristone is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Mifepristone is a strong inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
    Dihydroergotamine: (Contraindicated) Use of dihydroergotamine with mifepristone is contraindicated when mifepristone is used chronically for hormonal conditions, such as in the treatment of Cushing's syndrome. Mifepristone, a CYP3A4 inhibitor, is likely to increase ergot alkaloid concentrations and adverse effects, since dihydroergotamine is a CYP3A4 substrate with a narrow therapeutic index. Due to the slow elimination of mifepristone from the body, such interactions may be observed for a prolonged period after mifepristone administration.
    Diltiazem: (Moderate) Monitor blood pressure and heart rate if coadministration of diltiazem with mifepristone is necessary. Concurrent use may result in elevated diltiazem concentrations. Diltiazem is a CYP3A4 substrate and mifepristone is a strong CYP3A4 inhibitor.
    Diphenhydramine; Hydrocodone; Phenylephrine: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if chronic, concurrent use of mifepristone is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like mifepristone can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If mifepristone is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
    Diphenhydramine; Ibuprofen: (Moderate) Mifepristone significantly increased exposure of drugs metabolized by CYP2C8/2C9 in interaction studies. Therefore, when mifepristone is used chronically, as in the treatment of Cushing's syndrome, use caution with coadministered CYP2C8/2C9 substrates, including the NSAIDs. Use the lowest doses of the substrate and patients should be monitored closely for adverse reactions.
    Diphenhydramine; Naproxen: (Moderate) Mifepristone significantly increased exposure of drugs metabolized by CYP2C8/2C9 in interaction studies. Therefore, when mifepristone is used chronically, as in the treatment of Cushing's syndrome, use caution with coadministered CYP2C8/2C9 substrates, including the NSAIDs. Use the lowest doses of the substrate and patients should be monitored closely for adverse reactions.
    Disopyramide: (Contraindicated) When mifepristone is used chronically for hormonal conditions, such as Cushing's disease, the concomitant use of CYP3A substrates with narrow therapeutic index, such as disopyramide, is contraindicated. Disopyramide administration is associated with QT prolongation and torsade de pointes (TdP). Disopyramide is a substrate for CYP3A4. Drugs with a possible risk for QT prolongation that are also CYP3A4 inhibitors include mifepristone. Life-threatening interactions have been reported with the coadministration of disopyramide with other CYP3A4 inhibitors with a potential to prolong the QT interval. Due to the slow elimination of mifepristone from the body, such interactions may be observed for a prolonged period after mifepristone administration.
    Docetaxel: (Major) Avoid coadministration of docetaxel with mifepristone if possible due to increased plasma concentrations of docetaxel. If concomitant use of docetaxel with chronic mifepristone is unavoidable, closely monitor for docetaxel-related adverse reactions and consider a 50% dose reduction of docetaxel. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown. Docetaxel is a CYP3A4 substrate and mifepristone is a strong CYP3A4 inhibitor. Concomitant use with another strong CYP3A4 inhibitor increased docetaxel exposure by 2.2-fold.
    Dofetilide: (Major) Coadministration of dofetilide and mifepristone is not recommended as concurrent use may increase the risk of QT prolongation. Dofetilide, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Mifepristone is associated with dose-related prolongation of the QT interval. Additionally, dofetilide is metabolized to a small extent by CYP3A4, and inhibitors of CYP3A4, such as mifepristone, could increase systemic dofetilide exposure, further increasing the risk for QT prolongation.
    Dolasetron: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), mifepristone and dolasetron should be used together cautiously. Mifepristone has also been associated with dose-dependent prolongation of the QT interval. To minimize the risk of QT prolongation, the lowest effective dose should always be used. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram. Coadministration may increase the risk of QT prolongation.
    Dolutegravir; Rilpivirine: (Major) Avoid use together if possible due to the risk of elevated rilpivirine exposure and a combined risk for QT prolongation. Consider alternatives to rilpivirine when coadministered with a drug with a known risk of QT prolongation and torsade de pointes (TdP), such as mifepristone when it is used for chronic hormonal conditions, such as Cushing's syndrome. Mifepristone is an inhibitor of CYP3A4; rilpivirine is a CYP3A4 substrate. Coadministration is likely to increase rilpivirine plasma concentrations. Monitor for rilpivirine-related side effects, including rash, mood changes or depression, fast, irregular heart rate, and hepatotoxicity. To minimize the risk of QT prolongation, the lowest effect dose of mifepristone should always be used.
    Donepezil: (Moderate) Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy. Donepezil is considered a drug with a known risk of TdP. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with donepezil include mifepristone. To minimize the risk of QT prolongation, the lowest effective dose of mifepristone should always be used.
    Donepezil; Memantine: (Moderate) Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy. Donepezil is considered a drug with a known risk of TdP. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with donepezil include mifepristone. To minimize the risk of QT prolongation, the lowest effective dose of mifepristone should always be used.
    Doravirine: (Minor) Coadministration of doravirine and chronic mifepristone therapy may result in increased doravirine plasma concentrations. Doravirine is a CYP3A4 substrate; mifepristone is a strong inhibitor. In drug interaction studies, concurrent use of strong CYP3A4 inhibitors increased doravirine exposure by more than 3-fold; however, this increase was not considered clinically significant. The clinical significance of CYP450 inhibition with short-term use of mifepristone for termination of pregnancy is unknown.
    Doravirine; Lamivudine; Tenofovir disoproxil fumarate: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as mifepristone. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions. (Minor) Coadministration of doravirine and chronic mifepristone therapy may result in increased doravirine plasma concentrations. Doravirine is a CYP3A4 substrate; mifepristone is a strong inhibitor. In drug interaction studies, concurrent use of strong CYP3A4 inhibitors increased doravirine exposure by more than 3-fold; however, this increase was not considered clinically significant. The clinical significance of CYP450 inhibition with short-term use of mifepristone for termination of pregnancy is unknown.
    Doxepin: (Minor) Due to a possible risk for QT prolongation and torsade de pointes (TdP), mifepristone and tricyclic antidepressants should be used together cautiously. Mifepristone has been associated with dose-dependent prolongation of the QT interval. There is no experience with high exposure or concomitant use with other QT prolonging drugs. To minimize the risk of QT prolongation, the lowest effective dose should always be used. Drugs with a possible risk for QT prolongation and torsades de pointes that should be used cautiously with mifepristone include tricyclic antidepressants.
    Doxercalciferol: (Moderate) Cytochrome P450 enzyme inhibitors, such as mifepristone, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy.
    Doxorubicin: (Moderate) Avoid coadministration of mifepristone and doxorubicin if possible. Mifepristone is an inhibitor of CYP3A4 and may also inhibit P-glycoprotein (P-gp); doxorubicin is a major substrate of both P-gp and CYP3A4. Clinically significant interactions have been reported when doxorubicin was coadministered with inhibitors of CYP3A4 and/or P-gp, resulting in increased concentration and clinical effect of doxorubicin. When mifepristone is used chronically for hormonal conditions, as in the treatment of Cushing's disease, increased concentrations of CYP3A substrates are expected, and any drug interactions that do occur may be prolonged due to mifepristone's long duration of action. If not possible to avoid use of these drugs together, closely monitor for increased side effects of doxorubicin including myelosuppression and cardiotoxicity.
    Dronabinol: (Moderate) Use caution if coadministration of dronabinol with mifepristone is necessary; monitor for an increase in dronabinol-related CNS adverse reactions (e.g., cognitive impairment, euphoria, dizziness, confusion, somnolence, or changes in moods or behaviors) if mifepristone is used chronically for hormonal conditions such as Cushing's syndrome. A dose reduction of dronabinol may be needed in some patients to reduce the risk of central nervous system (CNS) symptoms. Dronabinol is a CYP2C9 and 3A4 substrate; mifepristone is an inhibitor of CYP3A4. Concomitant use may result in elevated plasma concentrations of dronabinol. Due to the slow elimination of mifepristone from the body, such interactions may be observed for a prolonged period after mifepristone administration.
    Dronedarone: (Contraindicated) Because of the potential for torsades de pointes, concurrent use of dronedarone and mifepristone is contraindicated. Mifepristone has been associated with dose-dependent prolongation of the QT interval. There is no experience with high exposure or concomitant use with other QT prolonging drugs. Dronedarone administration is associated with a dose-related increase in the QTc interval. The increase in QTc is approximately 10 milliseconds at doses of 400 mg twice daily (the FDA-approved dose) and up to 25 milliseconds at doses of 1600 mg twice daily. Although there are no studies examining the effects of dronedarone in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation. The concomitant use of dronedarone with other drugs that prolong the QTc may induce Torsade de Pointes (TdP) and is contraindicated.
    Droperidol: (Major) Droperidol should not be used in combination with any drug known to have potential to prolong the QT interval, such as mifepristone. Droperidol administration is associated with an established risk for QT prolongation and torsade de pointes (TdP). Some cases have occurred in patients with no known risk factors for QT prolongation and some cases have been fatal. If coadministration cannot be avoided, use extreme caution; initiate droperidol at a low dose and increase the dose as needed to achieve the desired effect. Mifepristone has been associated with dose-dependent prolongation of the QT interval. There is no experience with high exposure or concomitant use with other QT prolonging drugs. To minimize the risk of QT prolongation, the lowest effective dose should always be used.
    Dutasteride; Tamsulosin: (Moderate) Use caution when administering tamsulosin with a moderate CYP3A4 inhibitor such as mifepristone. If concomitant use in necessary, monitor patient closely for increased side effects, including hypotension, since tamsulosin exposure may be increased. Tamsulosin is extensively metabolized by CYP3A4. In clinical evaluation, concomitant treatment with a strong CYP3A4 inhibitor resulted in significant increases in tamsulosin exposure; interactions with moderate CYP3A4 inhibitors have not been evaluated. However, mifepristone is expected to increase concentrations of CYP3A4 substrates. Due to the slow elimination of mifepristone from the body, any interactions that do occur may be prolonged.
    Duvelisib: (Major) Reduce duvelisib dose to 15 mg PO twice daily and monitor for increased toxicity of both drugs when coadministered with chronic mifepristone therapy. Coadministration may increase the exposure of both drugs. Duvelisib is a substrate and moderate inhibitor of CYP3A; mifepristone is a substrate and strong inhibitor of CYP3A. The increase in exposure to duvelisib is estimated to be approximately 2-fold when used concomitantly with strong CYP3A inhibitors such as mifepristone. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
    Edoxaban: (Major) When mifepristone is used for the termination of pregnancy, the concurrent use of anticoagulants is contraindicated due to the increased risk of serious bleeding. When mifepristone is used, concurrent use of some anticoagulants should be approached with caution. Use of edoxaban and mifepristone may result in increased concentrations of edoxaban. Edoxaban is a P-glycoprotein (P-gp) substrate and mifepristone may be a P-gp inhibitor. Monitor for increased adverse effects of edoxaban; no dose reduction is recommended for concomitant P-gp inhibitor use. However, if active pathological bleeding occurs, edoxaban should be discontinued. Due to the long duration of action of mifepristone, any drug interaction that occurs may be prolonged.
    Efavirenz: (Major) Avoid use together when possible; consider alternatives to efavirenz. The use of these drugs together may increase the risk for QT prolongation or other efavirenz-induced side effects and may reduce mifepristone efficacy. Concurrent use will increase the systemic exposure of efavirenz and decrease mifepristone exposure. Efavirenz is a CYP2B6 substrate and CYP3A4 inducer, while mifepristone is a CYP3A4 substrate and CYP2B6 inhibitor. In addition, careful monitoring for mifepristone efficacy is necessary. To minimize the risk of QT prolongation, the lowest effective dose of mifepristone should always be used. Also monitor for evavirenz-associated adverse reactions, such as nervous system or psychiatric symptoms, fast irregular heart rate, QT prolongation, hepatotoxicity, and rash. QT prolongation has been observed with use of efavirenz. Mifepristone, when given chronically for hormonal conditions such as Cushing's syndrome. has also been associated with dose-dependent prolongation of the QT interval.
    Efavirenz; Emtricitabine; Tenofovir: (Major) Avoid use together when possible; consider alternatives to efavirenz. The use of these drugs together may increase the risk for QT prolongation or other efavirenz-induced side effects and may reduce mifepristone efficacy. Concurrent use will increase the systemic exposure of efavirenz and decrease mifepristone exposure. Efavirenz is a CYP2B6 substrate and CYP3A4 inducer, while mifepristone is a CYP3A4 substrate and CYP2B6 inhibitor. In addition, careful monitoring for mifepristone efficacy is necessary. To minimize the risk of QT prolongation, the lowest effective dose of mifepristone should always be used. Also monitor for evavirenz-associated adverse reactions, such as nervous system or psychiatric symptoms, fast irregular heart rate, QT prolongation, hepatotoxicity, and rash. QT prolongation has been observed with use of efavirenz. Mifepristone, when given chronically for hormonal conditions such as Cushing's syndrome. has also been associated with dose-dependent prolongation of the QT interval. (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as mifepristone. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
    Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Major) Avoid use together when possible; consider alternatives to efavirenz. The use of these drugs together may increase the risk for QT prolongation or other efavirenz-induced side effects and may reduce mifepristone efficacy. Concurrent use will increase the systemic exposure of efavirenz and decrease mifepristone exposure. Efavirenz is a CYP2B6 substrate and CYP3A4 inducer, while mifepristone is a CYP3A4 substrate and CYP2B6 inhibitor. In addition, careful monitoring for mifepristone efficacy is necessary. To minimize the risk of QT prolongation, the lowest effective dose of mifepristone should always be used. Also monitor for evavirenz-associated adverse reactions, such as nervous system or psychiatric symptoms, fast irregular heart rate, QT prolongation, hepatotoxicity, and rash. QT prolongation has been observed with use of efavirenz. Mifepristone, when given chronically for hormonal conditions such as Cushing's syndrome. has also been associated with dose-dependent prolongation of the QT interval. (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as mifepristone. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
    Elagolix: (Major) Concomitant use of elagolix 200 mg twice daily and mifepristone for more than 1 month is not recommended. Limit concomitant use of elagolix 150 mg once daily and mifepristone to 6 months. Elagolix is a CYP3A substrate; mifepristone is a strong inhibitor of CYP3A. Coadministration may increase elagolix plasma concentrations. In drug interaction studies, coadministration of elagolix with another strong CYP3A inhibitor increased the Cmax and AUC of elagolix by 77% and 120%, respectively.
    Elagolix; Estradiol; Norethindrone acetate: (Major) Concomitant use of elagolix 200 mg twice daily and mifepristone for more than 1 month is not recommended. Limit concomitant use of elagolix 150 mg once daily and mifepristone to 6 months. Elagolix is a CYP3A substrate; mifepristone is a strong inhibitor of CYP3A. Coadministration may increase elagolix plasma concentrations. In drug interaction studies, coadministration of elagolix with another strong CYP3A inhibitor increased the Cmax and AUC of elagolix by 77% and 120%, respectively.
    Elbasvir; Grazoprevir: (Moderate) Administering elbasvir; grazoprevir with mifepristone may cause the plasma concentrations of all three drugs to increase; thereby increasing the potential for adverse effects (i.e., elevated ALT concentrations and hepatotoxicity). Mifepristone is a substrate and moderate inhibitor of CYP3A. Both elbasvir and grazoprevir are metabolized by CYP3A, and grazoprevir is also a weak CYP3A inhibitor. If these drugs are used together, closely monitor for signs of hepatotoxicity. (Moderate) Administering elbasvir; grazoprevir with mifepristone, RU-486 may cause the plasma concentrations of all three drugs to increase; thereby increasing the potential for adverse effects (i.e., elevated ALT concentrations and hepatotoxicity). Mifepristone is a substrate and moderate inhibitor of CYP3A. Both elbasvir and grazoprevir are metabolized by CYP3A, and grazoprevir is also a weak CYP3A inhibitor. If these drugs are used together, closely monitor for signs of hepatotoxicity.
    Eletriptan: (Contraindicated) Eletriptan is contraindicated with recent use (i.e., within 72 hours) of chronic mifepristone therapy due to the potential for increased eletriptan exposure. The clinical significance of this interaction is not established when mifepristone is used for pregnancy termination. Eletriptan is a sensitive substrate of CYP3A4; mifepristone is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the Cmax and AUC of eletriptan by 3-fold and 6-fold, respectively.
    Elexacaftor; tezacaftor; ivacaftor: (Major) If mifepristone and ivacaftor are taken together, administer ivacaftor at the usual recommended dose but reduce the frequency to twice weekly. Ivacaftor is a CYP3A substrate, and mifepristone is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased ivacaftor exposure by 8.5-fold. (Major) Reduce the dosing frequency of elexacaftor; tezacaftor; ivacaftor when coadministered with chronic mifepristone therapy; coadministration may increase elexacaftor; tezacaftor; ivacaftor exposure and adverse reactions. When combined, dose 2 elexacaftor/tezacaftor/ivacaftor combination tablets twice a week, approximately 3 to 4 days apart (i.e., Day 1 and Day 4). The evening dose of ivacaftor should not be taken. Elexacaftor, tezacaftor, and ivacaftor are CYP3A4 substrates (ivacaftor is a sensitive substrate); mifepristone is a strong CYP3A4 inhibitor. Coadministration of a strong CYP3A4 inhibitor increased elexacaftor exposure by 2.8- fold, tezacaftor exposure by 4.5-fold, and ivacaftor exposure by 15.6-fold. The significance of this interaction when mifepristone is used for pregnancy termination is unknown. (Major) Reduce the dosing frequency of tezacaftor; ivacaftor when coadministered with mifepristone; coadministration may increase tezacaftor; ivacaftor exposure and adverse reactions. When combined, dose 1 tezacaftor; ivacaftor combination tablet twice a week, approximately 3 to 4 days apart (i.e., Day 1 and Day 4). The evening dose of ivacaftor should not be taken. Both tezacaftor and ivacaftor are CYP3A substrates (ivacaftor is a sensitive substrate); mifepristone is a strong CYP3A inhibitor. Coadministration of a strong CYP3A inhibitor increased tezacaftor and ivacaftor exposure 4- and 15.6-fold, respectively.
    Eliglustat: (Major) Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Drugs with a possible risk for QT prolongation and torsade de pointes (TdP) that should be used cautiously and with close monitoring with eliglustat include mifepristone.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Major) Caution is advised when administering cobicistat with mifepristone because increased serum concentrations of either drug may occur. When mifepristone is used in the treatment of Cushing's syndrome, coadministration with cobicistat should be done only when necessary, and in such cases the dose of mifepristone should be limited to a maximum dose of 900 mg per day. In a patient already receiving cobicistat, initiate mifepristone at a dose of 300 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with cobicistat is initiated in a patient already receiving mifepristone 300 mg, dosage adjustments are not required. If therapy with cobicistat is initiated in a patient already receiving mifepristone 600 mg, reduce dose of mifepristone to 300 mg and titrate to a maximum of 600 mg if clinically indicated. If therapy with cobicistat is initiated in a patient already receiving 900 mg, reduce dose of mifepristone to 600 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with cobicistat is initiated in a patient already receiving 1,200 mg, reduce the mifepristone dose to 900 mg. Both mifepristone and cobicistat are substrates and strong inhibitors of CYP3A4.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Caution is advised when administering cobicistat with mifepristone because increased serum concentrations of either drug may occur. When mifepristone is used in the treatment of Cushing's syndrome, coadministration with cobicistat should be done only when necessary, and in such cases the dose of mifepristone should be limited to a maximum dose of 900 mg per day. In a patient already receiving cobicistat, initiate mifepristone at a dose of 300 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with cobicistat is initiated in a patient already receiving mifepristone 300 mg, dosage adjustments are not required. If therapy with cobicistat is initiated in a patient already receiving mifepristone 600 mg, reduce dose of mifepristone to 300 mg and titrate to a maximum of 600 mg if clinically indicated. If therapy with cobicistat is initiated in a patient already receiving 900 mg, reduce dose of mifepristone to 600 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with cobicistat is initiated in a patient already receiving 1,200 mg, reduce the mifepristone dose to 900 mg. Both mifepristone and cobicistat are substrates and strong inhibitors of CYP3A4. (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as mifepristone. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
    Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Major) Avoid use together if possible due to the risk of elevated rilpivirine exposure and a combined risk for QT prolongation. Consider alternatives to rilpivirine when coadministered with a drug with a known risk of QT prolongation and torsade de pointes (TdP), such as mifepristone when it is used for chronic hormonal conditions, such as Cushing's syndrome. Mifepristone is an inhibitor of CYP3A4; rilpivirine is a CYP3A4 substrate. Coadministration is likely to increase rilpivirine plasma concentrations. Monitor for rilpivirine-related side effects, including rash, mood changes or depression, fast, irregular heart rate, and hepatotoxicity. To minimize the risk of QT prolongation, the lowest effect dose of mifepristone should always be used.
    Emtricitabine; Rilpivirine; Tenofovir disoproxil fumarate: (Major) Avoid use together if possible due to the risk of elevated rilpivirine exposure and a combined risk for QT prolongation. Consider alternatives to rilpivirine when coadministered with a drug with a known risk of QT prolongation and torsade de pointes (TdP), such as mifepristone when it is used for chronic hormonal conditions, such as Cushing's syndrome. Mifepristone is an inhibitor of CYP3A4; rilpivirine is a CYP3A4 substrate. Coadministration is likely to increase rilpivirine plasma concentrations. Monitor for rilpivirine-related side effects, including rash, mood changes or depression, fast, irregular heart rate, and hepatotoxicity. To minimize the risk of QT prolongation, the lowest effect dose of mifepristone should always be used. (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as mifepristone. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
    Emtricitabine; Tenofovir disoproxil fumarate: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as mifepristone. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
    Enalapril; Felodipine: (Moderate) Concurrent use of felodipine and mifepristone should be approached with caution and conservative dosing of felodipine due to the potential for significant increases in felodipine exposure. Monitor for evidence of increased felodipine effects including decreased blood pressure and increased heart rate. Felodipine is a sensitive CYP3A4 substrate and mifepristone is a strong CYP3A4 inhibitor. Concurrent use of another strong CYP3A4 inhibitor increased felodipine AUC and half-life by approximately 8-fold and 2-fold, respectively.
    Encorafenib: (Major) Avoid coadministration of encorafenib and mifepristone due to increased encorafenib exposure and QT prolongation. If concurrent use cannot be avoided, reduce the encorafenib dose to one-third of the dose used prior to the addition of mifepristone. Monitor ECGs for QT prolongation and monitor electrolytes; correct hypokalemia and hypomagnesemia prior to treatment. Use the lowest effective dose of mifepristone. If mifepristone is discontinued, the original encorafenib dose may be resumed after 3 to 5 elimination half-lives of mifepristone. Encorafenib is a CYP3A4 substrate that has been associated with dose-dependent QT prolongation. When administered chronically, mifepristone is a strong CYP3A4 inhibitor that has been associated with dose-dependent QT prolongation. The clinical significance of mifepristone inhibition of CYP3A4 when used for pregnancy termination is not established. Coadministration of a strong CYP3A4 inhibitor with a single 50 mg dose of encorafenib (0.1 times the recommended dose) increased the encorafenib AUC and Cmax by 3-fold and 68%, respectively.
    Enflurane: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with mifepristone. Halogenated anesthetics can prolong the QT interval. Mifepristone has been associated with dose-dependent prolongation of the QT interval. There is no experience with high exposure or concomitant use with other QT prolonging drugs. To minimize the risk of QT prolongation, the lowest effective dose should always be used.
    Enfortumab vedotin: (Moderate) Monitor for signs of enfortumab vedotin-related adverse reactions if coadministration with mifepristone is necessary. Concomitant use may increase free monomethyl auristatin E (MMAE) exposure, which may increase the incidence or severity of enfortumab-vedotin toxicities. MMAE, the microtubule-disrupting component of enfortumab vedotin, is a CYP3A4 substrate; mifepristone is a strong CYP3A4 inhibitor. Clinical drug interaction studies have not been conducted for enfortumab vedotin. However, coadministration of another antibody-drug conjugate that contains MMAE with a strong CYP3A4 inhibitor increased the Cmax and AUC of MMAE by 25% and 34%, respectively, with no change in the total exposure of the antibody-drug conjugate. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
    Enoxaparin: (Major) When mifepristone is used for the termination of pregnancy, concurrent use of anticoagulants is contraindicated due to the increased risk of serious bleeding. Consider an alternative to mifepristone in these circumstances. When mifepristone is used chronically for other conditions, such as Cushing's disease, an interaction with low-molecular weight heparins is not expected; however, follow usual cautions and monitor as per standard of care.
    Entrectinib: (Major) Avoid coadministration of entrectinib with mifepristone due to additive risk of QT prolongation and increased entrectinib exposure resulting in increased treatment-related adverse effects. If coadministration cannot be avoided in adults and pediatric patients 12 years and older with BSA greater than 1.5 m2, reduce the entrectinib dose to 100 mg PO once daily. If mifepristone is discontinued, resume the original entrectinib dose after 3 to 5 elimination half-lives of mifepristone. Entrectinib is a CYP3A4 substrate that has been associated with QT prolongation; mifepristone is a strong CYP3A4 inhibitor that is associated with dose-related prolongation of the QT interval. Coadministration of a strong CYP3A4 inhibitor increased the AUC of entrectinib by 6-fold in a drug interaction study.
    Enzalutamide: (Major) When mifepristone is administered for the treatment of Cushing's syndrome, avoid coadministration of enzalutamide. When mifepristone is administered for pregnancy termination, follow-up assessment to verify that treatment has been successful is recommended in patients receiving enzalutamide. Coadministration may decrease mifepristone exposure reducing efficacy. Mifepristone is a CYP3A4 substrate; enzalutamide is a strong CYP3A4 inducer. The impact of CYP3A4 inducers on mifepristone efficacy is unknown.
    Eplerenone: (Contraindicated) Coadministration of mifepristone and eplerenone is contraindicated. Mifepristone potently inhibits the hepatic CYP3A4 isoenzyme and can increase the serum concentrations of eplerenone. Increased eplerenone concentrations may lead to a risk of developing hyperkalemia and hypotension.
    Erdafitinib: (Major) Avoid coadministration of erdafitinib and chronic mifepristone therapy due to the risk of increased plasma concentrations of erdafitinib. If concomitant use is unavoidable, closely monitor for erdafitinib-related adverse reactions and consider dose modifications as clinically appropriate. If mifepristone is discontinued, the dose of erdafitinib may be increased in the absence of drug-related toxicity. Erdafitinib is a substrate of CYP3A4 and CYP2C9. Mifepristone is a moderate CYP2C9 inhibitor and a strong CYP3A4 inhibitor. The mean ratios for the Cmax and AUC of erdafitinib were 105% and 134%, respectively, when coadministered with another strong CYP3A4 inhibitor. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
    Ergotamine: (Contraindicated) Use of ergotamine with mifepristone is contraindicated when mifepristone is used chronically for hormonal conditions, such as in the treatment of Cushing's syndrome. Mifepristone, a CYP3A4 inhibitor, is likely to increase ergot alkaloid concentrations and adverse effects, since ergotamine is a CYP3A4 substrate with a narrow therapeutic index. Due to the slow elimination of mifepristone from the body, such interactions may be observed for a prolonged period after mifepristone administration.
    Eribulin: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), mifepristone and eribulin should be used together cautiously. Mifepristone has been associated with dose-dependent prolongation of the QT interval. There is no experience with high exposure or concomitant use with other QT prolonging drugs. To minimize the risk of QT prolongation, the lowest effective dose should always be used. Eribulin has been associated with QT prolongation. If eribulin and another drug that prolongs the QT interval must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
    Erlotinib: (Major) Avoid coadministration of erlotinib with chronic mifepristone use if possible due to the increased risk of erlotinib-related adverse reactions. If concomitant use is unavoidable and severe reactions occur, reduce the dose of erlotinib by 50 mg decrements. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown. Erlotinib is a CYP3A4 substrate and mifepristone is a strong CYP3A4 inhibitor. Due to the slow elimination of mifepristone from the body, such interaction may be observed for a prolonged period after its administration. Coadministration with another strong CYP3A4 inhibitor increased erlotinib exposure by 67%.
    Erythromycin: (Major) Mifepristone has been associated with dose-dependent prolongation of the QT interval and is a CYP3A4 substrate. Drugs that are moderate CYP3A4 inhibitors that also prolong the QT interval, such as erythromycin, should be used with caution and close monitoring. To minimize the risk of QT prolongation and torsade de pointes (TdP), the lowest effective dose of mifepristone should always be used for the treatment of chronic endocrine conditions (Cushing's syndrome). There is no experience with high exposure o fmifepristone or concomitant use with other QT prolonging drugs. Erythromycin is also associated with prolongation of the QT interval and TdP. The use of mifepristone with CYP3A inhibitors may result in increased mifepristone concentrations and an increased risk of QT prolongation.
    Erythromycin; Sulfisoxazole: (Major) Mifepristone has been associated with dose-dependent prolongation of the QT interval and is a CYP3A4 substrate. Drugs that are moderate CYP3A4 inhibitors that also prolong the QT interval, such as erythromycin, should be used with caution and close monitoring. To minimize the risk of QT prolongation and torsade de pointes (TdP), the lowest effective dose of mifepristone should always be used for the treatment of chronic endocrine conditions (Cushing's syndrome). There is no experience with high exposure o fmifepristone or concomitant use with other QT prolonging drugs. Erythromycin is also associated with prolongation of the QT interval and TdP. The use of mifepristone with CYP3A inhibitors may result in increased mifepristone concentrations and an increased risk of QT prolongation.
    Escitalopram: (Moderate) Escitalopram has been associated with QT prolongation. Coadministration with other drugs that have a possible risk for QT prolongation and torsade de pointes (TdP), such as mifepristone, should be done with caution and close monitoring.
    Esomeprazole; Naproxen: (Moderate) Mifepristone significantly increased exposure of drugs metabolized by CYP2C8/2C9 in interaction studies. Therefore, when mifepristone is used chronically, as in the treatment of Cushing's syndrome, use caution with coadministered CYP2C8/2C9 substrates, including the NSAIDs. Use the lowest doses of the substrate and patients should be monitored closely for adverse reactions.
    Estazolam: (Major) Estazolam should be used with mifepristone only with caution and consideration of appropriate estazolam dosage reduction. CNS depression, impaired motor and/or cognitive performance may occur due to increased estazolam exposure. In some patients, estazolam discontinuation may be necessary. Mifepristone inhibits CYP3A4 when it is used chronically in the treatment of hormonal conditions, such as Cushing's disease. Coadministration of mifepristone may lead to a significant increase in serum concentrations of drugs that are CYP3A4 substrates like estazolam. Due to the slow elimination of mifepristone from the body, such interactions may be observed for a prolonged period after mifepristone administration.
    Esterified Estrogens: (Minor) Estrogens are partially metabolized by CYP3A4. Drugs that inhibit CYP3A4 such as mifepristone may increase plasma concentrations of estrogens and cause estrogen-related side effects such as nausea and breast tenderness. Patients receiving estrogens should be monitored for an increase in adverse events.
    Esterified Estrogens; Methyltestosterone: (Minor) Estrogens are partially metabolized by CYP3A4. Drugs that inhibit CYP3A4 such as mifepristone may increase plasma concentrations of estrogens and cause estrogen-related side effects such as nausea and breast tenderness. Patients receiving estrogens should be monitored for an increase in adverse events.
    Estradiol: (Contraindicated) Mifepristone is a progesterone-receptor antagonist and will interfere with the effectiveness of hormonal contraceptives. Therefore, non-hormonal contraceptive methods should be used in Cushing's patients taking mifepristone.
    Estradiol; Progesterone: (Moderate) Use caution if coadministration of mifepristone with progesterone is necessary, as the systemic exposure of progesterone may be increased resulting in an increase in treatment-related adverse reactions. Mifepristone is a strong CYP3A4 inhibitor. Progesterone is metabolized primarily by hydroxylation via a CYP3A4. This interaction does not apply to vaginal preparations of progesterone (e.g., Crinone, Endometrin).
    Estropipate: (Minor) Estrogens are partially metabolized by CYP3A4. Drugs that inhibit CYP3A4 such as mifepristone may increase plasma concentrations of estrogens and cause estrogen-related side effects such as nausea and breast tenderness. Patients receiving estrogens should be monitored for an increase in adverse events.
    Eszopiclone: (Major) The total dose of eszopiclone should not exceed 2 mg when administered with chronic mifepristone therapy. Coadministration may increase eszopiclone exposure resulting in increased risk of next-day psychomotor or memory impairment and decreased ability to perform tasks requiring full mental alertness such as driving. CYP3A4 is a primary metabolic pathway for eszopiclone; mifepristone is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased eszopiclone exposure by 2.2-fold. The clinical significance of this interaction when mifepristone is used for pregnancy termination is not established.
    Etodolac: (Moderate) Mifepristone significantly increased exposure of drugs metabolized by CYP2C8/2C9 in interaction studies. Therefore, when mifepristone is used chronically, as in the treatment of Cushing's syndrome, use caution with coadministered CYP2C8/2C9 substrates, including the NSAIDs. Use the lowest doses of the substrate and patients should be monitored closely for adverse reactions.
    Etonogestrel: (Contraindicated) Mifepristone is a progesterone-receptor antagonist and will interfere with the effectiveness of hormonal contraceptives. Therefore, non-hormonal contraceptive methods should be used in Cushing's patients taking mifepristone.
    Etonogestrel; Ethinyl Estradiol: (Contraindicated) Mifepristone is a progesterone-receptor antagonist and will interfere with the effectiveness of hormonal contraceptives. Therefore, non-hormonal contraceptive methods should be used in Cushing's patients taking mifepristone.
    Everolimus: (Major) Avoid coadministration of everolimus with mifepristone due to the risk of increased everolimus-related adverse reactions. If concomitant use is unavoidable in patients receiving everolimus for either kidney or liver transplant, closely monitor everolimus whole blood trough concentrations. Everolimus is a sensitive CYP3A4 substrate and a P-glycoprotein (P-gp) substrate. Mifepristone is a strong CYP3A4 and P-gp inhibitor. Coadministration with another strong CYP3A4/P-gp inhibitor increased the AUC of everolimus by 15-fold. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
    Ezetimibe; Simvastatin: (Contraindicated) When mifepristone is used in the treatment of Cushing's syndrome, coadministration is contraindicated based on studies demonstrating significant simvastatin exposure increases which may lead to an increased risk of myopathy and rhabdomyolysis. Consider interruption of simvastatin therapy during use of mifepristone for pregnancy termination. Due to the slow elimination of mifepristone from the body, such interactions may be observed for a prolonged period after mifepristone administration. Mifepristone is a strong CYP3A4 inhibitor; simvastatin is a sensitive CYP3A4 substrate. Coadministration of mifepristone and simvastatin increased simvastatin and simvastatin acid exposure by 10.4-fold and 15.7-fold, respectively, in drug interaction studies.
    Ezogabine: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), mifepristone and ezogabine should be used together cautiously. Mifepristone has been associated with dose-dependent prolongation of the QT interval. There is no experience with high exposure or concomitant use with other QT prolonging drugs. To minimize the risk of QT prolongation, the lowest effective dose should always be used. Ezogabine has also been associated with QT prolongation. The manufacturer of ezogabine recommends caution during concurrent use of medications known to increase the QT interval.
    Famotidine; Ibuprofen: (Moderate) Mifepristone significantly increased exposure of drugs metabolized by CYP2C8/2C9 in interaction studies. Therefore, when mifepristone is used chronically, as in the treatment of Cushing's syndrome, use caution with coadministered CYP2C8/2C9 substrates, including the NSAIDs. Use the lowest doses of the substrate and patients should be monitored closely for adverse reactions.
    Fedratinib: (Major) Avoid coadministration of fedratinib with mifepristone as concurrent use may increase fedratinib exposure. If concurrent use cannot be avoided, reduce the dose of fedratinib to 200 mg PO once daily. If mifepristone is discontinued, increase the fedratinib dose as follows: 300 mg PO once daily for 2 weeks and then 400 mg PO once daily thereafter as tolerated. Fedratinib is a CYP3A4 substrate; mifepristone is a strong CYP3A4 inhibitor. The significance of the interaction when mifepristone is used for pregnancy termination is unknown. Coadministration of another strong CYP3A4 inhibitor increased fedratinib exposure by 3-fold.
    Felodipine: (Moderate) Concurrent use of felodipine and mifepristone should be approached with caution and conservative dosing of felodipine due to the potential for significant increases in felodipine exposure. Monitor for evidence of increased felodipine effects including decreased blood pressure and increased heart rate. Felodipine is a sensitive CYP3A4 substrate and mifepristone is a strong CYP3A4 inhibitor. Concurrent use of another strong CYP3A4 inhibitor increased felodipine AUC and half-life by approximately 8-fold and 2-fold, respectively.
    Fenoprofen: (Moderate) Mifepristone significantly increased exposure of drugs metabolized by CYP2C8/2C9 in interaction studies. Therefore, when mifepristone is used chronically, as in the treatment of Cushing's syndrome, use caution with coadministered CYP2C8/2C9 substrates, including the NSAIDs. Use the lowest doses of the substrate and patients should be monitored closely for adverse reactions.
    Fentanyl: (Contraindicated) Coadministration of fentanyl is contraindicated when mifepristone is used chronically, such as in the treatment of Cushing's syndrome or other hormonal conditions. Mifepristone inhibits CYP3A4. Coadministration of mifepristone may lead to a significant increase in serum concentrations of drugs that are CYP3A4 substrates and that have a narrow therapeutic index, such as fentanyl. The increase in fentanyl concentrations can increase the risk for serious CNS depression and respiratory depression, particularly when mifepristone is added after a stable dose of fentanyl is achieved. Due to the slow elimination of mifepristone from the body, such interactions may be observed for a prolonged period after mifepristone administration.
    Fesoterodine: (Major) Limit the dose of fesoterodine to 4 mg once daily in adults and pediatric patients weighing more than 35 kg if coadministered with mifepristone. Avoid use of fesoterodine and mifepristone in pediatric patients weighing 25 to 35 kg. Concurrent use may increase fesoterodine exposure. Fesoterodine is a CYP3A4 substrate and mifepristone is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor led to approximately a doubling of the overall exposure of 5-hydroxymethyl tolterodine (5-HMT), the active metabolite of fesoterodine.
    Finerenone: (Contraindicated) Concomitant use of finerenone and mifepristone is contraindicated. Concomitant use may increase finerenone exposure and the risk for finerenone-related adverse reactions. Finerenone is a CYP3A substrate and mifepristone is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased overall exposure to finerenone by more than 400%.
    Fingolimod: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), mifepristone and fingolimod should be used together cautiously. Mifepristone has been associated with dose-dependent prolongation of the QT interval. There is no experience with high exposure or concomitant use with other QT prolonging drugs. To minimize the risk of QT prolongation, the lowest effective dose should always be used. Fingolimod initiation results in decreased heart rate and may prolong the QT interval. After the first fingolimod dose, overnight monitoring with continuous ECG in a medical facility is advised for patients taking QT prolonging drugs with a known risk of TdP. Fingolimod has not been studied in patients treated with drugs that prolong the QT interval, but drugs that prolong the QT interval have been associated with cases of TdP in patients with bradycardia.
    Flecainide: (Moderate) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering mifepristone with flecainide. Mifepristone has been associated with dose-dependent prolongation of the QT interval. Flecainide, a Class IC antiarrhythmic, is also associated with a possible risk for QT prolongation and/or TdP; flecainide increases the QT interval, but largely due to prolongation of the QRS interval. Although causality for TdP has not been established for flecainide, patients receiving concurrent drugs which have the potential for QT prolongation may have an increased risk of developing proarrhythmias.
    Flibanserin: (Moderate) The concomitant use of flibanserin and multiple weak CYP3A4 inhibitors, including mifepristone, may increase flibanserin concentrations, which may increase the risk of flibanserin-induced adverse reactions. Therefore, patients should be monitored for hypotension, syncope, somnolence, or other adverse reactions, and the risks of combination therapy with multiple weak CYP3A4 inhibitors and flibanserin should be discussed with the patient.
    Fluconazole: (Contraindicated) Fluconazole has been associated with QT prolongation and rare cases of torsades de pointes (TdP). The concurrent use of fluconazole and other drugs that prolong the QT and are CYP3A4 substrates is contraindicated due to the risk of life-threatening arrhythmias such as TdP. Coadministration of fluconazole with drugs that are CYP3A4 substrates may result in an elevated plasma concentration of the interacting drug, causing an increased risk for adverse events, such as QT prolongation. Drugs that prolong QT and are substrates for CYP3A4 that are contraindicated with fluconazole include mifepristone.
    Fluoxetine: (Major) Avoid use together. Consider alternative therapy to fluoxetine if possible. QT prolongation and torsade de pointes (TdP) have been reported in patients treated with fluoxetine. Drugs with a possible risk for QT prolongation and TdP include mifepristone, when given chronically for hormonal conditions, such as the treatment of Cushing's syndrome. If use of these drugs together is medically necessary, limit the mifepristone dose to the lowest effective dose and monitor closely. Because of the prolonged actions of both mifepristone and fluoxetine, any drug interactions that occur may be prolonged.
    Fluoxetine; Olanzapine: (Major) Avoid use together. Consider alternative therapy to fluoxetine if possible. QT prolongation and torsade de pointes (TdP) have been reported in patients treated with fluoxetine. Drugs with a possible risk for QT prolongation and TdP include mifepristone, when given chronically for hormonal conditions, such as the treatment of Cushing's syndrome. If use of these drugs together is medically necessary, limit the mifepristone dose to the lowest effective dose and monitor closely. Because of the prolonged actions of both mifepristone and fluoxetine, any drug interactions that occur may be prolonged. (Moderate) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering olanzapine with mifepristone. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances. Mifepristone has also been associated with dose-dependent prolongation of the QT interval. There is no experience with high exposure or concomitant use with other QT prolonging drugs. To minimize the risk of QT prolongation, the lowest effective dose should always be used.
    Fluphenazine: (Minor) Due to a possible risk for QT prolongation and torsade de pointes (TdP), mifepristone and fluphenazine should be used together cautiously. Mifepristone has been associated with dose-dependent prolongation of the QT interval. There is no experience with high exposure or concomitant use with other QT prolonging drugs. To minimize the risk of QT prolongation, the lowest effective dose should always be used. Drugs with a possible risk for QT prolongation that should be used cautiously with mifepristone include fluphenazine.
    Flurbiprofen: (Moderate) Mifepristone significantly increased exposure of drugs metabolized by CYP2C8/2C9 in interaction studies. Therefore, when mifepristone is used chronically, as in the treatment of Cushing's syndrome, use caution with coadministered CYP2C8/2C9 substrates, including the NSAIDs. Use the lowest doses of the substrate and patients should be monitored closely for adverse reactions.
    Fluvastatin: (Major) When mifepristone is used chronically in the treatment of hormonal conditions, such as Cushing's syndrome, and given with fluvastatin, the lowest dose of fluvastatin should be used and the patient monitored closely for an increased risk for fluvastatin-related adverse events, such as myopathy and rhabdomyolysis. Consider an alternative to fluvastatin if possible. Mifepristone inhibits CYP2C8/C9 and CYP3A4. In drug interaction studies, significantly increased the exposure of fluvastatin. Fluvastatin is primarily metabolized by CYP2C9, and to a lesser extent, CYP2C8 and CYP3A4. Due to the slow elimination of mifepristone from the body, such interactions may be observed for a prolonged period after mifepristone administration.
    Fluvoxamine: (Moderate) Coadministration of drugs that have been associated with QT prolongation, such as mifepristone and fluvoxamine, may increase the risk of QT prolongation or torsade de pointes. In addition, mifepristone is a CYP3A4 substrate and fluvoxamine is a moderate CYP3A4 inhibitor, which may further increase the risk of QT prolongation.
    Fondaparinux: (Major) When mifepristone, RU-486 (Mifeprex) is used for the termination of pregnancy, concurrent use of anticoagulants is contraindicated due to the increased risk of serious bleeding. When mifepristone (Korlym) is used, concurrent use of some anticoagulants should be approached with caution.
    Food: (Moderate) The incidence of marijuana associated adverse effects may change following coadministration with mifepristone. Mifepristone is an inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of marijuana's most psychoactive compound, delta-9-tetrahydrocannabinol (Delta-9-THC). When given concurrently with mifepristone, the amount of Delta-9-THC converted to the active metabolite 11-hydroxy-delta-9-tetrahydrocannabinol (11-OH-THC) may be reduced. These changes in Delta-9-THC and 11-OH-THC plasma concentrations may result in an altered marijuana adverse event profile.
    Fosamprenavir: (Major) Caution is advised when administering fosamprenavir with mifepristone because increased serum concentrations of either drug may occur. When mifepristone is used in the treatment of Cushing's syndrome, coadministration with fosamprenavir should be done only when necessary, and in such cases the dose of mifepristone should be limited to a maximum dose of 900 mg per day. In a patient already receiving fosamprenavir, initiate mifepristone at a dose of 300 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with fosamprenavir is initiated in a patient already receiving mifepristone 300 mg, dosage adjustments are not required. If therapy with fosamprenavir is initiated in a patient already receiving mifepristone 600 mg, reduce dose of mifepristone to 300 mg and titrate to a maximum of 600 mg if clinically indicated. If therapy with fosamprenavir is initiated in a patient already receiving 900 mg, reduce dose of mifepristone to 600 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with fosamprenavir is initiated in a patient already receiving 1,200 mg, reduce the mifepristone dose to 900 mg. Both mifepristone and fosamprenavir are substrates and strong inhibitors of CYP3A4.
    Foscarnet: (Major) When possible, avoid concurrent use of foscarnet with other drugs known to prolong the QT interval, such as mifepristone. Foscarnet has been associated with postmarketing reports of both QT prolongation and torsade de pointes (TdP). Mifepristone has been associated with dose-dependent prolongation of the QT interval. To minimize the risk of QT prolongation, the lowest effective dose of mifepristone should always be used. If these drugs are administered together, obtain an electrocardiogram and electrolyte concentrations before and periodically during treatment.
    Fosphenytoin: (Major) Avoid coadministration of mifepristone and CYP3A inducers such as fosphenytoin. It is not known if lowered mifepristone serum levels would lead to reduced response or therapeutic failure. Mifepristone, when used chronically for hormonal conditions such as Cushing's disease, is a CYP2C9 inhibitor and is likely to increase plasma concentrations of fosphenytoin, a sensitive CYP2C9 substrate. Due to the slow elimination of mifepristone from the body, any drug interactions that occur may be prolonged. If use together is medically necessary, monitor the patient closely to ensure the proper therapeutic response is obtained to both medications. Monitor for signs/symptoms of phenytoin toxicity.
    Fostamatinib: (Moderate) Monitor for fostamatinib toxicities that may require fostamatinib dose reduction (i.e., elevated hepatic enzymes, neutropenia, high blood pressure, severe diarrhea) if given concurrently with a strong CYP3A4 inhibitor. Concomitant use of fostamatinib with a strong CYP3A4 inhibitor increases exposure to the major active metabolite, R406, which may increase the risk of adverse reactions. R406 is extensively metabolized by CYP3A4; mifepristone is a strong CYP3A4 inhibitor. Coadministration of fostamatinib with another strong CYP3A4 inhibitor increased R406 AUC by 102% and Cmax by 37%.
    Fostemsavir: (Major) Avoid use of mifepristone with QT interval prolonging drugs. Mifepristone is associated with dose-related prolongation of the QT interval. Supratherapeutic doses of fostemsavir (2,400 mg twice daily, four times the recommended daily dose) have been shown to cause QT prolongation. Fostemsavir causes dose-dependent QT prolongation.
    Gefitinib: (Moderate) Monitor for an increase in gefitinib-related adverse reactions if coadministration with chronic mifepristone therapy is necessary. Gefitinib is a CYP3A4 substrate and mifepristone is a strong CYP3A4 inhibitor. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown. Coadministration with another strong CYP3A4 inhibitor increased gefitinib exposure by 80%.
    Gemifloxacin: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), concurrent use of mifepristone and gemifloxacin should be avoided if possible. Mifepristone has been associated with dose-dependent prolongation of the QT interval. There is no experience with high exposure or concomitant use with other QT prolonging drugs. To minimize the risk of QT prolongation, the lowest effective dose should always be used. Gemifloxacin may prolong the QT interval in some patients. The maximal change in the QTc interval occurs approximately 5 to 10 hours following oral administration of gemifloxacin. The likelihood of QTc prolongation may increase with increasing dose of the drug; therefore, the recommended dose should not be exceeded especially in patients with renal or hepatic impairment where the Cmax and AUC are slightly higher.
    Gemtuzumab Ozogamicin: (Moderate) Use gemtuzumab ozogamicin and mifepristone together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. To minimize the risk of QT prolongation, the lowest effective dose of mifepristone should always be used. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. Mifepristone has been associated with dose-dependent prolongation of the QT interval.
    Gilteritinib: (Major) Consider an alternative to mifepristone during treatment with gilteritinib due to increased gilteritinib exposure and the potential for additive QT prolongation. If coadministration is required, frequently monitor for gilteritinib-related adverse effects and cardiac toxicity. To minimize the risk of QT prolongation, the lowest effective dose of mifepristone should always be used. Interrupt therapy and reduce the gilteritinib dose if serious or life-threatening toxicity occurs. Gilteritinib is a CYP3A4 substrate; mifepristone is a strong CYP3A4 inhibitor. Coadministration of a strong CYP3A4 inhibitor increased the gilteritinib AUC by 120% in a drug interaction study. Both drugs have been associated with QT prolongation. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
    Glasdegib: (Major) Consider an alternative to mifepristone during treatment with glasdegib due to the potential for additive QT prolongation and increased glasdegib exposure. If coadministration cannot be avoided, monitor for increased glasdegib-related adverse events and for increased risk of QT prolongation with more frequent ECG monitoring; use the lowest effective dose of mifepristone. Glasdegib is a CYP3A4 substrate that may cause QT prolongation and ventricular arrhythmias including ventricular fibrillation and ventricular tachycardia. Mifepristone is a strong CYP3A4 inhibitor that has been associated with dose-dependent prolongation of the QT interval. Coadministration of a strong CYP3A4 inhibitor increased the glasdegib AUC by 2.4-fold in a drug interaction study. The clinical significance of inhibition of CYP3A4 with the short-term use of mifepristone for termination of pregnancy is unknown.
    Glecaprevir; Pibrentasvir: (Moderate) Caution is advised with the coadministration of glecaprevir and mifepristone as coadministration may increase serum concentrations of glecaprevir and increase the risk of adverse effects. Glecaprevir is a substrate of P-glycoprotein (P-gp); mifepristone is a P-gp inhibitor. (Moderate) Caution is advised with the coadministration of pibrentasvir and mifepristone as coadministration may increase serum concentrations of pibrentasvir and increase the risk of adverse effects. Pibrentasvir is a substrate of P-glycoprotein (P-gp); mifepristone is an inhibitor of P-gp.
    Goserelin: (Major) Avoid use of mifepristone with QT interval prolonging drugs including goserelin. Mifepristone is associated with dose-related prolongation of the QT interval. Androgen deprivation therapy (i.e., goserelin) may also prolong the QT/QTc interval.
    Granisetron: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), mifepristone and granisetron should be used together cautiously. Mifepristone has been associated with dose-dependent prolongation of the QT interval. There is no experience with high exposure or concomitant use with other QT prolonging drugs. To minimize the risk of QT prolongation, the lowest effective dose should always be used. Granisetron has been associated with QT prolongation. According to the manufacturer, use of granisetron with drugs known to prolong the QT interval or are arrhythmogenic, may result in clinical consequences.
    Grapefruit juice: (Major) Advise patients to avoid grapefruit juice while taking mifepristone due to increased mifepristone exposure. Mifepristone is a CYP3A4 substrate and grapefruit juice is a strong CYP3A4 inhibitor.
    Guaifenesin; Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if chronic, concurrent use of mifepristone is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like mifepristone can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If mifepristone is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
    Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if chronic, concurrent use of mifepristone is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like mifepristone can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If mifepristone is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
    Halogenated Anesthetics: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with mifepristone. Halogenated anesthetics can prolong the QT interval. Mifepristone has been associated with dose-dependent prolongation of the QT interval. There is no experience with high exposure or concomitant use with other QT prolonging drugs. To minimize the risk of QT prolongation, the lowest effective dose should always be used.
    Haloperidol: (Major) Avoid use together if possible due to an additive risk for QT prolongation and elevated haloperidol concentrations, which may lead to drug-related adverse events. Consider alternatives to haloperidol if possible. If use together is necessary, some patients may require haloperidol dose reduction; closely monitor for adverse events. Mifepristone inhibits CYP3A4 and has been associated with QT prolongation. QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation. Mild to moderate increases in haloperidol exposure have been reported during concurrent use with inhibitors of CYP3A4.
    Halothane: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with mifepristone. Halogenated anesthetics can prolong the QT interval. Mifepristone has been associated with dose-dependent prolongation of the QT interval. There is no experience with high exposure or concomitant use with other QT prolonging drugs. To minimize the risk of QT prolongation, the lowest effective dose should always be used.
    Heparin: (Major) When mifepristone is used for the termination of pregnancy, concurrent use of anticoagulants is contraindicated due to the increased risk of serious bleeding. Consider an alternative to mifepristone in these circumstances. When mifepristone is used chronically for other conditions, such as Cushing's disease, an interaction with heparin is not expected; however, follow usual cautions and monitor as per standard of care.
    Histrelin: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., histrelin) outweigh the potential risks of QT prolongation in patients receiving mifepristone. To minimize the risk of QT prolongation, the lowest effective dose of mifepristone should always be used. Mifepristone has been associated with dose-dependent prolongation of the QT interval. Androgen deprivation therapy may prolong the QT/QTc interval.
    Homatropine; Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if chronic, concurrent use of mifepristone is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like mifepristone can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If mifepristone is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
    Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if chronic, concurrent use of mifepristone is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like mifepristone can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If mifepristone is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
    Hydrocodone; Ibuprofen: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if chronic, concurrent use of mifepristone is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like mifepristone can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If mifepristone is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown. (Moderate) Mifepristone significantly increased exposure of drugs metabolized by CYP2C8/2C9 in interaction studies. Therefore, when mifepristone is used chronically, as in the treatment of Cushing's syndrome, use caution with coadministered CYP2C8/2C9 substrates, including the NSAIDs. Use the lowest doses of the substrate and patients should be monitored closely for adverse reactions.
    Hydrocodone; Phenylephrine: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if chronic, concurrent use of mifepristone is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like mifepristone can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If mifepristone is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
    Hydrocodone; Potassium Guaiacolsulfonate: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if chronic, concurrent use of mifepristone is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like mifepristone can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If mifepristone is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
    Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if chronic, concurrent use of mifepristone is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like mifepristone can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If mifepristone is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
    Hydrocodone; Pseudoephedrine: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if chronic, concurrent use of mifepristone is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like mifepristone can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If mifepristone is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
    Hydroxychloroquine: (Major) Avoid coadministration of mifepristone and hydroxychloroquine due to an increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Mifepristone has been associated with dose-dependent prolongation of the QT interval.
    Hydroxyzine: (Major) Avoid coadministration of hydroxyzine with mifepristone due to the risk for additive QT prolongation and torsade de pointes (TdP). Mifepristone has been associated with dose-dependent prolongation of the QT interval. Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP.
    Ibrexafungerp: (Major) Decrease the ibrexafungerp dose to 150 mg PO every 12 hours for 1 day if administered concurrently with mifepristone. Coadministration may result in increased ibrexafungerp exposure and toxicity. Ibrexafungerp is a CYP3A substrate and mifepristone is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the AUC and Cmax of ibrexafungerp by 5.8-fold and 2.5-fold, respectively.
    Ibrutinib: (Major) Avoid the concomitant use of ibrutinib and chronic mifepristone therapy; ibrutinib plasma concentrations may increase resulting in severe ibrutinib toxicity (e.g., hematologic toxicity, bleeding, infection). Ibrutinib is a CYP3A4 substrate; mifepristone is a strong CYP3A4 inhibitor. When ibrutinib was administered with multiple doses of other strong CYP3A4 inhibitors, the Cmax and AUC values of ibrutinib were increased significantly. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
    Ibuprofen: (Moderate) Mifepristone significantly increased exposure of drugs metabolized by CYP2C8/2C9 in interaction studies. Therefore, when mifepristone is used chronically, as in the treatment of Cushing's syndrome, use caution with coadministered CYP2C8/2C9 substrates, including the NSAIDs. Use the lowest doses of the substrate and patients should be monitored closely for adverse reactions.
    Ibuprofen; Oxycodone: (Moderate) Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression and sedation if concurrent use of mifepristone is necessary. If mifepristone is discontinued, consider increasing the oxycodone dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oxycodone is a CYP3A4 substrate, and coadministration with a strong CYP3A4 inhibitor like mifepristone can increase oxycodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of oxycodone. If mifepristone is discontinued, oxycodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to oxycodone. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown. (Moderate) Mifepristone significantly increased exposure of drugs metabolized by CYP2C8/2C9 in interaction studies. Therefore, when mifepristone is used chronically, as in the treatment of Cushing's syndrome, use caution with coadministered CYP2C8/2C9 substrates, including the NSAIDs. Use the lowest doses of the substrate and patients should be monitored closely for adverse reactions.
    Ibuprofen; Pseudoephedrine: (Moderate) Mifepristone significantly increased exposure of drugs metabolized by CYP2C8/2C9 in interaction studies. Therefore, when mifepristone is used chronically, as in the treatment of Cushing's syndrome, use caution with coadministered CYP2C8/2C9 substrates, including the NSAIDs. Use the lowest doses of the substrate and patients should be monitored closely for adverse reactions.
    Idelalisib: (Major) Caution is advised when administering idelalisib with mifepristone because increased serum concentrations of either drug may occur. When mifepristone is used in the treatment of Cushing's syndrome, coadministration with idelalisib should be done only when necessary, and in such cases the dose of mifepristone should be limited to a maximum dose of 900 mg per day. In a patient already receiving idelalisib, initiate mifepristone at a dose of 300 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with idelalisib is initiated in a patient already receiving mifepristone 300 mg, dosage adjustments are not required. If therapy with idelalisib is initiated in a patient already receiving mifepristone 600 mg, reduce dose of mifepristone to 300 mg and titrate to a maximum of 600 mg if clinically indicated. If therapy with idelalisib is initiated in a patient already receiving 900 mg, reduce dose of mifepristone to 600 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with idelalisib is initiated in a patient already receiving 1,200 mg, reduce the mifepristone dose to 900 mg. Additionally, monitor patients frequently for signs and symptoms of idelalisib-related adverse reactions (e.g., hepatotoxicity, diarrhea, neutropenia, and infection). Both mifepristone and idelalisib are substrates and strong inhibitors of CYP3A4. Coadministration with another strong CYP3A4 inhibitor increased idelalisib exposure by 1.8-fold.
    Iloperidone: (Major) Avoid coadministration of iloperidone and chronic mifepristone therapy due to the potential for QT prolongation; increased iloperidone exposure may also occur. If coadministration cannot be avoided, reduce the iloperidone dose by one-half and use the lowest effective dose of mifepristone. If mifepristone is discontinued, increase the iloperidone dose to the previous level. Iloperidone is a CYP3A4 substrate that has been associated with QT prolongation. Mifepristone is a strong CYP3A4 inhibitor that also prolongs the QT interval. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
    Imatinib: (Moderate) Monitor for an increase in imatinib-related adverse reactions if coadministration with mifepristone is necessary. Imatinib is a CYP3A substrate and mifepristone is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased imatinib exposure by 40%.
    Imipramine: (Minor) Due to a possible risk for QT prolongation and torsade de pointes (TdP), mifepristone and tricyclic antidepressants should be used together cautiously. Mifepristone has been associated with dose-dependent prolongation of the QT interval. There is no experience with high exposure or concomitant use with other QT prolonging drugs. To minimize the risk of QT prolongation, the lowest effective dose should always be used. Drugs with a possible risk for QT prolongation and torsades de pointes that should be used cautiously with mifepristone include tricyclic antidepressants.
    Indinavir: (Major) Caution is advised when administering indinavir with mifepristone because increased serum concentrations of either drug may occur. When mifepristone is used in the treatment of Cushing's syndrome, coadministration with indinavir should be done only when necessary, and in such cases the dose of mifepristone should be limited to a maximum dose of 900 mg per day. In a patient already receiving indinavir, initiate mifepristone at a dose of 300 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with indinavir is initiated in a patient already receiving mifepristone 300 mg, dosage adjustments are not required. If therapy with indinavir is initiated in a patient already receiving mifepristone 600 mg, reduce dose of mifepristone to 300 mg and titrate to a maximum of 600 mg if clinically indicated. If therapy with indinavir is initiated in a patient already receiving 900 mg, reduce dose of mifepristone to 600 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with indinavir is initiated in a patient already receiving 1,200 mg, reduce the mifepristone dose to 900 mg. Both mifepristone and indinavir are substrates and strong inhibitors of CYP3A4.
    Indomethacin: (Moderate) Mifepristone significantly increased exposure of drugs metabolized by CYP2C8/2C9 in interaction studies. Therefore, when mifepristone is used chronically, as in the treatment of Cushing's syndrome, use caution with coadministered CYP2C8/2C9 substrates, including the NSAIDs. Use the lowest doses of the substrate and patients should be monitored closely for adverse reactions.
    Infigratinib: (Major) Avoid concomitant use of infigratinib and mifepristone. Coadministration may increase infigratinib exposure, increasing the risk for adverse effects. Infigratinib is a CYP3A4 substrate and mifepristone is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the AUC of infigratinib by 622%.
    Inotuzumab Ozogamicin: (Major) Avoid coadministration of inotuzumab ozogamicin with mifepristone due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. To minimize the risk of QT prolongation, the lowest effective dose of mifepristone should always be used. Mifepristone has also been associated with dose-dependent prolongation of the QT interval. Inotuzumab has been associated with QT interval prolongation.
    Irinotecan Liposomal: (Major) Avoid administration of chronic mifepristone therapy during treatment with irinotecan and for at least 1 week prior to starting therapy unless there are no therapeutic alternatives. Irinotecan is a CYP3A4 substrate and mifepristone is a strong CYP3A4 inhibitor. Concomitant use may increase systemic exposure of irinotecan. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
    Irinotecan: (Major) Avoid administration of chronic mifepristone therapy during treatment with irinotecan and for at least 1 week prior to starting therapy unless there are no therapeutic alternatives. Irinotecan is a CYP3A4 substrate and mifepristone is a strong CYP3A4 inhibitor. Concomitant use may increase systemic exposure of irinotecan. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
    Isavuconazonium: (Moderate) Concomitant use of isavuconazonium with mifepristone may result in increased serum concentrations of both drugs. Mifepristone is a substrate and inhibitor of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate and moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
    Isoflurane: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with mifepristone. Halogenated anesthetics can prolong the QT interval. Mifepristone has been associated with dose-dependent prolongation of the QT interval. There is no experience with high exposure or concomitant use with other QT prolonging drugs. To minimize the risk of QT prolongation, the lowest effective dose should always be used.
    Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) When mifepristone is administered for the treatment of Cushing's syndrome, avoid coadministration of rifampin. When mifepristone is administered for pregnancy termination, follow-up assessment to verify that treatment has been successful is recommended in patients receiving rifampin. Coadministration may decrease mifepristone exposure reducing efficacy. Mifepristone is a CYP3A4 substrate; rifampin is a strong CYP3A4 inducer. The impact of CYP3A4 inducers on mifepristone efficacy is unknown.
    Isoniazid, INH; Rifampin: (Major) When mifepristone is administered for the treatment of Cushing's syndrome, avoid coadministration of rifampin. When mifepristone is administered for pregnancy termination, follow-up assessment to verify that treatment has been successful is recommended in patients receiving rifampin. Coadministration may decrease mifepristone exposure reducing efficacy. Mifepristone is a CYP3A4 substrate; rifampin is a strong CYP3A4 inducer. The impact of CYP3A4 inducers on mifepristone efficacy is unknown.
    Isradipine: (Moderate) Monitor blood pressure and heart rate if coadministration of isradipine with mifepristone is necessary. Concurrent use may result in elevated isradipine concentrations. Isradipine is a CYP3A4 substrate and mifepristone is a strong CYP3A4 inhibitor.
    Istradefylline: (Major) Do not exceed 20 mg once daily of istradefylline if administered with mifepristone as istradefylline exposure and adverse effects may increase. Mifepristone is a strong CYP3A4 inhibitor. Istradefylline exposure was increased by 2.5-fold when administered with a strong inhibitor in a drug interaction study.
    Itraconazole: (Major) Avoid coadministration of mifepristone with itraconazole due to the risk of additive QT prolongation; the exposure of both drugs may also be increased. If concomitant use of mifepristone is necessary for the treatment of Cushing's syndrome in a patient already receiving itraconazole, initiate mifepristone at a dose of 300 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with itraconazole is initiated in a patient already receiving mifepristone 300 mg, dosage adjustments are not required. If therapy with itraconazole is initiated in a patient already receiving mifepristone 600 mg, reduce dose of mifepristone to 300 mg and titrate to a maximum of 600 mg if clinically indicated. If therapy with itraconazole is initiated in a patient already receiving 900 mg, reduce dose of mifepristone to 600 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with itraconazole is initiated in a patient already receiving 1,200 mg, reduce the mifepristone dose to 900 mg. Both mifepristone and itraconazole are substrates and strong inhibitors of CYP3A4 that are associated with QT prolongation.
    Ivabradine: (Major) Avoid coadministration of ivabradine and mifepristone as increased concentrations of ivabradine are possible. Ivabradine is primarily metabolized by CYP3A4; mifepristone inhibits CYP3A4. Increased ivabradine concentrations may result in bradycardia exacerbation and conduction disturbances. Due to the slow elimination of mifepristone from the body, drug interactions may be prolonged.
    Ivacaftor: (Major) If mifepristone and ivacaftor are taken together, administer ivacaftor at the usual recommended dose but reduce the frequency to twice weekly. Ivacaftor is a CYP3A substrate, and mifepristone is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased ivacaftor exposure by 8.5-fold.
    Ivosidenib: (Major) Avoid coadministration of ivosidenib with mifepristone due to increased plasma concentrations of ivosidenib and additive QT prolongation. If concomitant use is unavoidable, reduce the dose of ivosidenib to 250 mg PO once daily. Monitor ECGs for QTc prolongation and monitor electrolytes, correcting any electrolyte abnormalities as clinically appropriate. If mifepristone is discontinued, wait at least 5 half-lives of mifepristone before increasing the dose of ivosidenib to the recommended dose of 500 mg PO once daily. Ivosidenib is a CYP3A4 substrate that has been associated with QTc prolongation and ventricular arrhythmias. Mifepristone is a strong CYP3A4 inhibitor associated with dose-dependent QT prolongation. Coadministration with another strong CYP3A4 inhibitor increased ivosidenib single-dose AUC to 269% of control, with no change in Cmax.
    Ixabepilone: (Moderate) Caution should be used when administering mild or moderate CYP3A4 inhibitors during treatment with ixabepilone, and alternative therapeutic agents that do not inhibit CYP3A4 should be considered. Patients receiving CYP3A4 inhibitors during treatment with ixabepilone should be monitored closely for acute toxicities (e.g., frequent monitoring of peripheral blood counts between cycles of ixabepilone). In some patients, a dose reduction of ixabepilone should be considered. Ixabepilone is a CYP3A4 substrate, and mifepristone is a CYP3A4 inhibitor. If mifepristone is discontinued, allow 7 days to elapse before increasing the ixabepilone dose; the prolonged action of mifepristone may result in prolonged duration of any interactions.
    Ketoconazole: (Major) Avoid coadministration of mifepristone with ketoconazole due to the risk of additive QT prolongation; the exposure of both drugs may also be increased. If concomitant use of mifepristone is necessary for the treatment of Cushing's syndrome in a patient already receiving ketoconazole, initiate mifepristone at a dose of 300 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with ketoconazole is initiated in a patient already receiving mifepristone 300 mg, dosage adjustments are not required. If therapy with ketoconazole is initiated in a patient already receiving mifepristone 600 mg, reduce dose of mifepristone to 300 mg and titrate to a maximum of 600 mg if clinically indicated. If therapy with ketoconazole is initiated in a patient already receiving 900 mg, reduce dose of mifepristone to 600 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with ketoconazole is initiated in a patient already receiving 1,200 mg, reduce the mifepristone dose to 900 mg. Both mifepristone and ketoconazole are substrates and strong inhibitors of CYP3A4 that are associated with QT prolongation.
    Ketoprofen: (Moderate) Mifepristone significantly increased exposure of drugs metabolized by CYP2C8/2C9 in interaction studies. Therefore, when mifepristone is used chronically, as in the treatment of Cushing's syndrome, use caution with coadministered CYP2C8/2C9 substrates, including the NSAIDs. Use the lowest doses of the substrate and patients should be monitored closely for adverse reactions.
    Ketorolac: (Moderate) Mifepristone significantly increased exposure of drugs metabolized by CYP2C8/2C9 in interaction studies. Therefore, when mifepristone is used chronically, as in the treatment of Cushing's syndrome, use caution with coadministered CYP2C8/2C9 substrates, including the NSAIDs. Use the lowest doses of the substrate and patients should be monitored closely for adverse reactions.
    Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as mifepristone. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
    Lansoprazole; Naproxen: (Moderate) Mifepristone significantly increased exposure of drugs metabolized by CYP2C8/2C9 in interaction studies. Therefore, when mifepristone is used chronically, as in the treatment of Cushing's syndrome, use caution with coadministered CYP2C8/2C9 substrates, including the NSAIDs. Use the lowest doses of the substrate and patients should be monitored closely for adverse reactions.
    Lapatinib: (Major) Avoid coadministration of lapatinib with mifepristone due to increased plasma concentrations of lapatinib; QT prolongation may also occur. If concomitant use is unavoidable, decrease the dose of lapatinib to 500 mg PO once daily; use the lowest effective dose of mifepristone to reduce the risk of QT prolongation. Monitor ECGs for QT prolongation and monitor electrolytes; correct any electrolyte abnormalities prior to treatment. If mifepristone is discontinued, increase lapatinib to the indicated dose after a washout period of approximately 1 week. Lapatinib is a CYP3A4 substrate that has been associated with concentration-dependent QT prolongation; ventricular arrhythmias and torsade de pointes (TdP) have also been reported in postmarketing experience. Mifepristone is a strong CYP3A4 inhibitor that has also been associated with dose-dependent prolongation of the QT interval. Concomitant use with another strong CYP3A4 inhibitor increased lapatinib exposure by 3.6-fold and increased the half-life of lapatinib by 1.7-fold. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
    Larotrectinib: (Major) Avoid coadministration of larotrectinib with chronic mifepristone use due to increased larotrectinib exposure resulting in increased treatment-related adverse effects. If coadministration cannot be avoided, reduce the larotrectinib dose by 50%. If mifepristone is discontinued, resume the original larotrectinib dose after 3 to 5 elimination half-lives of mifepristone. Larotrectinib is a CYP3A4 substrate; mifepristone is a strong CYP3A4 inhibitor. Coadministration of a strong CYP3A4 inhibitor increased the AUC of larotrectinib by 4.3-fold in a drug interaction study. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
    Lefamulin: (Major) Avoid coadministration of lefamulin with mifepristone as concurrent use may increase the risk of QT prolongation; concurrent use may also increase exposure from lefamulin tablets which may increase the risk of adverse effects. Lefamulin is a CYP3A4 and P-gp substrate that has a concentration dependent QTc prolongation effect. The pharmacodynamic interaction potential to prolong the QT interval of the electrocardiogram between lefamulin and other drugs that effect cardiac conduction is unknown. Mifepristone is a P-gp and strong CYP3A4 inhibitor that is also associated with QT prolongation. Coadministration of a combined P-gp and strong CYP3A4 inhibitor increased the exposure of oral and intravenous lefamulin by 165% and 31%, respectively.
    Lemborexant: (Major) Avoid coadministration of lemborexant and mifepristone as concurrent use is expected to significantly increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; mifepristone is a strong CYP3A4 inhibitor. Coadministration of lemborexant with another strong CYP3A4 inhibitor increased the lemborexant AUC by up to 4.5-fold. Due to the long half-life of mifepristone, a drug interaction is possible for a prolonged period after discontinuation of mifepristone. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
    Lenvatinib: (Major) Avoid coadministration of lenvatinib with mifepristone due to the risk of QT prolongation. Prolongation of the QT interval has been reported with lenvatinib therapy. Mifepristone has been associated with dose-dependent prolongation of the QT interval.
    Lesinurad: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of mifepristone; monitor for potential reduction in efficacy. Mifepristone is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
    Lesinurad; Allopurinol: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of mifepristone; monitor for potential reduction in efficacy. Mifepristone is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
    Letermovir: (Moderate) An increase in the plasma concentration of mifepristone may occur if given with letermovir. In patients who are also receiving treatment with cyclosporine, the magnitude of this interaction may be amplified. Mifepristone is a CYP3A4 substrate. Letermovir is a moderate CYP3A4 inhibitor; however, when given with cyclosporine, the combined effect on CYP3A4 substrates may be similar to a strong CYP3A4 inhibitor.
    Leuprolide: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving mifepristone. To minimize the risk of QT prolongation, the lowest effective dose of mifepristone should always be used. Mifepristone has been associated with dose-dependent prolongation of the QT interval. Androgen deprivation therapy may prolong the QT/QTc interval.
    Leuprolide; Norethindrone: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving mifepristone. To minimize the risk of QT prolongation, the lowest effective dose of mifepristone should always be used. Mifepristone has been associated with dose-dependent prolongation of the QT interval. Androgen deprivation therapy may prolong the QT/QTc interval.
    Levamlodipine: (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with mifepristone is necessary; adjust the dose of amlodipine as clinically appropriate. Mifepristone is a strong CYP3A inhibitor and amlodipine is a CYP3A substrate. Coadministration with a moderate CYP3A4 inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. Strong CYP3A4 inhibitors may increase the plasma concentrations of amlodipine to a greater extent.
    Levofloxacin: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), concurrent use of mifepristone and levofloxacin should be avoided if possible. Mifepristone has been associated with dose-dependent prolongation of the QT interval. There is no experience with high exposure or concomitant use with other QT prolonging drugs. To minimize the risk of QT prolongation, the lowest effective dose should always be used. Levofloxacin has been associated with prolongation of the QT interval and infrequent cases of arrhythmia. Rare cases of TdP have been spontaneously reported during postmarketing surveillance in patients receiving levofloxacin.
    Levomethadyl: (Contraindicated) Use of mifepristone, a CYP3A4 inhibitor, may lead to an increase in levomethadyl serum concentrations, which can lead to fatal respiratory depression and QT prolongation. Use together is contraindicated. Coadministration of mifepristone may lead to an increase in serum levels of drugs that are CYP3A4 substrates that have a narrow therapeutic index, such as levomethadyl. Due to the slow elimination of mifepristone from the body, such interactions may be observed for a prolonged period after mifepristone administration.
    Lithium: (Moderate) Lithium should be used cautiously with mifepristone. Lithium has been associated with QT prolongation. Mifepristone has been associated with dose-dependent prolongation of the QT interval. There is no experience with high exposure or concomitant use with other QT prolonging drugs. To minimize the risk of QT prolongation, the lowest effective dose should always be used.
    Lofexidine: (Moderate) Monitor ECG and use the lowest effective dose of mifepristone if lofexidine is coadministered due to the potential for additive QT prolongation. Lofexidine prolongs the QT interval. In addition, there are postmarketing reports of torsade de pointes. Mifepristone has been associated with dose-dependent prolongation of the QT interval.
    Lonafarnib: (Contraindicated) Concomitant use of lonafarnib and mifepristone is contraindicated as use together increases the exposure and risk of adverse effects from both drugs. Consider alternatives. If concomitant use of mifepristone is absolutely necessary for the treatment of Cushing's syndrome in a patient already receiving lonafarnib, initiate mifepristone at a dose of 300 mg and titrate to a maximum of 900 mg/day if clinically indicated. Monitor closely for lonafarnib and mifepristone toxicity. If a patient is taking mifepristone daily and lonafarnib is necessary, consult the product literature for recommended dose adjustments. Lonafarnib is a sensitive CYP3A4 and CYP2C9 substrate and strong CYP3A4 inhibitor; mifepristone is a CYP3A4 substrate and strong CYP3A4 and moderate CYP2C9 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the exposure of lonafarnib by 425%.
    Long-acting beta-agonists: (Moderate) Mifepristone has been associated with dose-dependent prolongation of the QT interval. There is no experience with high exposure or concomitant use with other QT prolonging drugs. To minimize the risk of QT prolongation, the lowest effective dose of mifepristone should always be used. Drugs with a possible risk for QT prolongation that should be used cautiously with mifepristone include the beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Loperamide: (Moderate) Loperamide should be used cautiously and with close monitoring with mifepristone. At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, torsade de pointes (TdP), and cardiac arrest. Mifepristone has been associated with dose-dependent prolongation of the QT interval. There is no experience with high exposure or concomitant use with other QT prolonging drugs. To minimize the risk of QT prolongation, the lowest effective dose of mifepristone should always be used. In addition, the plasma concentrations of loperamide, a CYP3A4 and P-glycoprotein (P-gp) substrate, may be increased when administered concurrently with mifepristone, a potent CYP3A4 and P-gp inhibitor, further increasing the risk of toxicity. If these drugs are used together, monitor for cardiac toxicities (i.e., syncope, ventricular tachycardia, QT prolongation, TdP, cardiac arrest) and other loperamide-associated adverse reactions, such as CNS effects.
    Loperamide; Simethicone: (Moderate) Loperamide should be used cautiously and with close monitoring with mifepristone. At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, torsade de pointes (TdP), and cardiac arrest. Mifepristone has been associated with dose-dependent prolongation of the QT interval. There is no experience with high exposure or concomitant use with other QT prolonging drugs. To minimize the risk of QT prolongation, the lowest effective dose of mifepristone should always be used. In addition, the plasma concentrations of loperamide, a CYP3A4 and P-glycoprotein (P-gp) substrate, may be increased when administered concurrently with mifepristone, a potent CYP3A4 and P-gp inhibitor, further increasing the risk of toxicity. If these drugs are used together, monitor for cardiac toxicities (i.e., syncope, ventricular tachycardia, QT prolongation, TdP, cardiac arrest) and other loperamide-associated adverse reactions, such as CNS effects.
    Lopinavir; Ritonavir: (Major) Avoid coadministration of lopinavir with mifepristone due to the potential for additive QT prolongation. If use together is necessary, obtain a baseline ECG to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Monitor patients for lopinavir-related adverse effects (e.g., diarrhea, nausea, vomiting, fast irregular heartbeat, hypokalemia, pancreatic or hepatic dysfunction). Mifepristone is a strong CYP3A4 inhibitor and may lead to an increase in serum concentrations of lopinavir, a CYP3A4 substrate. Mifepristone is also associated with dose-related prolongation of the QT interval. Lopinavir is associated with QT prolongation. (Major) Caution is advised when administering ritonavir with mifepristone because increased serum concentrations of either drug may occur. When mifepristone is used in the treatment of Cushing's syndrome, coadministration with ritonavir should be done only when necessary, and in such cases the dose of mifepristone should be limited to a maximum dose of 900 mg per day. In a patient already receiving ritonavir, initiate mifepristone at a dose of 300 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with ritonavir is initiated in a patient already receiving mifepristone 300 mg, dosage adjustments are not required. If therapy with ritonavir is initiated in a patient already receiving mifepristone 600 mg, reduce dose of mifepristone to 300 mg and titrate to a maximum of 600 mg if clinically indicated. If therapy with ritonavir is initiated in a patient already receiving 900 mg, reduce dose of mifepristone to 600 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with ritonavir is initiated in a patient already receiving 1,200 mg, reduce the mifepristone dose to 900 mg. Both mifepristone and ritonavir are substrates and strong inhibitors of CYP3A4.
    Lorlatinib: (Major) Avoid coadministration of lorlatinib with mifepristone due to increased plasma concentrations of lorlatinib, which may increase the incidence and severity of adverse reactions. If concomitant use is unavoidable, reduce the starting dose of lorlatinib from 100 mg to 75 mg once daily, or from 75 mg to 50 mg once daily. If mifepristone is discontinued, resume the original dose of lorlatinib after 3 half-lives of mifepristone. Lorlatinib is a CYP3A substrate and mifepristone is a strong CYP3A inhibitor. Coadministration with another strong CYP3A4 inhibitor increased lorlatinib exposure by 42%. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
    Lovastatin: (Contraindicated) When mifepristone is used in the treatment of Cushing's syndrome, coadministration is contraindicated based on studies demonstrating significant lovastatin exposure increases which may lead to an increased risk of myopathy and rhabdomyolysis. Consider interruption of lovastatin therapy during use of mifepristone for pregnancy termination. Mifepristone inhibits CYP3A4; lovastatin is a CYP3A4 substrate. Coadministration of mifepristone increases serum levels drugs metabolized via CYP3A4 with narrow therapeutic indexes, such as lovastatin. Due to the slow elimination of mifepristone from the body, such interactions may be observed for a prolonged period after administration.
    Lovastatin; Niacin: (Contraindicated) When mifepristone is used in the treatment of Cushing's syndrome, coadministration is contraindicated based on studies demonstrating significant lovastatin exposure increases which may lead to an increased risk of myopathy and rhabdomyolysis. Consider interruption of lovastatin therapy during use of mifepristone for pregnancy termination. Mifepristone inhibits CYP3A4; lovastatin is a CYP3A4 substrate. Coadministration of mifepristone increases serum levels drugs metabolized via CYP3A4 with narrow therapeutic indexes, such as lovastatin. Due to the slow elimination of mifepristone from the body, such interactions may be observed for a prolonged period after administration.
    Low Molecular Weight Heparins: (Major) When mifepristone is used for the termination of pregnancy, concurrent use of anticoagulants is contraindicated due to the increased risk of serious bleeding. Consider an alternative to mifepristone in these circumstances. When mifepristone is used chronically for other conditions, such as Cushing's disease, an interaction with low-molecular weight heparins is not expected; however, follow usual cautions and monitor as per standard of care.
    Lumacaftor; Ivacaftor: (Major) If mifepristone and ivacaftor are taken together, administer ivacaftor at the usual recommended dose but reduce the frequency to twice weekly. Ivacaftor is a CYP3A substrate, and mifepristone is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased ivacaftor exposure by 8.5-fold.
    Lumacaftor; Ivacaftor: (Major) Lumacaftor; ivacaftor may decrease the therapeutic efficacy of mifepristone; avoid concurrent use if possible. If coadministration is necessary, monitor efficacy and adjust drug dosages as necessary. Lumacaftor; ivacaftor dosage adjustment is not required when mifepristone is started in a patient already taking lumacaftor; ivacaftor. However, if lumacaftor; ivacaftor is initiated in a patient already taking mifepristone, reduce the dose of lumacaftor; ivacaftor to 1 tablet PO daily or 1 packet of oral granules every other day for the first week of treatment, and then increase to the usual recommended daily dose. This dosage adjustment is also necessary if lumacaftor; ivacaftor therapy has been interrupted for more than 1 week and re-initiated while the patient is taking mifepristone. The 1-week lead-in period at the lower lumacaftor; ivacaftor dosage allows for lumacaftor's induction of CYP3A to reach steady state. Mifepristone is a substrate and strong inhibitor of CYP3A. Ivacaftor is a CYP3A substrate, and lumacaftor is a strong CYP3A inducer. Lumacaftor's induction of CYP3A may decrease the systemic exposure of mifepristone and decrease its therapeutic efficacy. Although mifepristone is a strong CYP3A4 inhibitor, net ivacaftor exposure at steady state is not expected to exceed that achieved with ivacaftor monotherapy (i.e., 150 mg PO every 12 hours) because of lumacaftor's CYP3A induction. In pharmacokinetic studies, coadministration of lumacaftor; ivacaftor with another strong CYP3A4 inhibitor increased ivacaftor exposure by 4.3-fold.
    Lumateperone: (Major) Avoid coadministration of lumateperone and mifepristone as concurrent use may increase lumateperone exposure and the risk of adverse effects. Lumateperone is a CYP3A4 substrate; mifepristone is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased lumateperone exposure by approximately 4-fold. Due to the long half-life of mifepristone, a drug interaction is possible for a prolonged period after discontinuation of mifepristone. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
    Lurasidone: (Major) Avoid use together if possible due to increased lurasidone exposure. The lurasidone adult dose should not exceed 40 mg/day if coadministered with moderate CYP3A4 inhibitors, such as mifepristone. Monitor closely for lurasidone-related adverse events, including increased CNS depression, changes in moods or behavirors, movement disorders, and leukopenia . Mifepristone, when used chronically for hormonal conditions such as Cushing's syndrome, inhibits CYP3A4. Lurasidone is primarily metabolized by CYP3A4 and use of mifepristone is expected to increase lurasidone exposure.
    Lurbinectedin: (Major) Avoid coadministration of lurbinectedin and mifepristone due to the risk of increased lurbinectedin exposure which may increase the incidence of lurbinectedin-related adverse reactions. Lurbinectedin is a CYP3A substrate and mifepristone is a strong CYP3A inhibitor. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
    Macimorelin: (Major) Avoid concurrent administration of macimorelin with drugs that prolong the QT interval, such as mifepristone. Use of these drugs together may increase the risk of developing torsade de pointes-type ventricular tachycardia. Sufficient washout time of drugs that are known to prolong the QT interval prior to administration of macimorelin is recommended. Treatment with macimorelin has been associated with an increase in the corrected QT (QTc) interval. Mifepristone has been associated with dose-dependent prolongation of the QT interval. To minimize the risk of QT prolongation, the lowest effective dose of mifepristone should always be used.
    Maprotiline: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), mifepristone and maprotiline should be used together cautiously. Mifepristone has been associated with dose-dependent prolongation of the QT interval. There is no experience with high exposure or concomitant use with other QT prolonging drugs. To minimize the risk of QT prolongation, the lowest effective dose should always be used. Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and TdP tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs.
    Maraviroc: (Moderate) Use caution if coadministration of maraviroc with mifepristone is necessary, due to a possible increase in maraviroc exposure. Maraviroc is a CYP3A/P-glycoprotein (P-gp) substrate and mifepristone is a CYP3A4/P-gp inhibitor. Monitor for an increase in adverse effects with concomitant use.
    Meclofenamate Sodium: (Moderate) Mifepristone significantly increased exposure of drugs metabolized by CYP2C8/2C9 in interaction studies. Therefore, when mifepristone is used chronically, as in the treatment of Cushing's syndrome, use caution with coadministered CYP2C8/2C9 substrates, including the NSAIDs. Use the lowest doses of the substrate and patients should be monitored closely for adverse reactions.
    Mefenamic Acid: (Moderate) Mifepristone significantly increased exposure of drugs metabolized by CYP2C8/2C9 in interaction studies. Therefore, when mifepristone is used chronically, as in the treatment of Cushing's syndrome, use caution with coadministered CYP2C8/2C9 substrates, including the NSAIDs. Use the lowest doses of the substrate and patients should be monitored closely for adverse reactions.
    Mefloquine: (Major) Concurrent use may increase the serum concentrations of mefloquine, further increasing the risk for mefloquine-related adverse effects. including dizziness, changes in moods or behaviors, vision changes, and QT prolongation. Mefloquine is metabolized by CYP3A4 and P-glycoprotein (P-gp). Mifepristone is a potent and prolonged inhibitor of CYP3A4 and P-gp. In addition, mifepristone may cause QT prolongation. Based on the long terminal half-life of mifepristone after reaching steady state, at least 2 weeks should elapse after cessation of mifepristone, when used for chronic conditions, before initiating or increasing the dose of any interacting concomitant medication. Discontinuation or dose reduction of mefloquine may be necessary if mifepristone must be used.
    Meloxicam: (Moderate) Mifepristone significantly increased exposure of drugs metabolized by CYP2C8/2C9 in interaction studies. Therefore, when mifepristone is used chronically, as in the treatment of Cushing's syndrome, use caution with coadministered CYP2C8/2C9 substrates, including the NSAIDs. Use the lowest doses of the substrate and patients should be monitored closely for adverse reactions.
    Meperidine; Promethazine: (Moderate) Promethazine carries a possible risk of QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with promethazine include mifepristone.
    Metformin; Repaglinide: (Moderate) Repaglinide dose reductions and increased frequency of glucose monitoring may be required when mifepristone (for chronic conditions) is prescribed concurrently. When mifepristone is used chronically, such as with Cushing's syndrome, the lowest dose of repaglinide should be used that results in proper clinical response and tolerance. Monitor closely for hypoglycemia and adverse reactions. In some patients, a lower dose of repaglinide will be needed. Repaglinide is a CYP2C8 substrate. Mifepristone significantly increases exposure of drugs metabolized by CYP2C8, and can be expected to increase repaglinide exposure. Due to the slow elimination of mifepristone from the body, such interactions may be observed for a prolonged period after mifepristone administration.
    Metformin; Saxagliptin: (Moderate) Monitor patients for hypoglycemia if saxagliptin and mifepristone are used together; dosage reduction of saxagliptin may be needed in some patients. In patients taking CYP3A substrates, the manufacturer of mifepristone recommends that the lowest dose of the CYP3A substrate that achieves the proper clinical response and tolerability be used. When potent CYP3A inhibitors are used, the initial dose of saxagliptin should be limited to 2.5 mg/day; mifepristone is a CYP3A inhibitor and has been noted to increase concentrations of CYP3A substrates. Due to the slow elimination of mifepristone from the body, such interactions may be observed for a prolonged period after mifepristone administration.
    Methadone: (Major) Avoid use together if possible. Coadministration of mifepristone may lead to a significant increase in serum concentrations of methadone. The increase in methadone concentrations can increase the risk for serious CNS and respiratory depression or QT prolongation, particularly when mifepristone is added after a stable dose of methadone is achieved. Methadone is a substrate for CYP3A4, CYP2B6, and P-glycoprotein (P-gp). Mifepristone, when used chronically for hormonal conditions such as Cushing's disease, inhibits CYP3A4, 2B6 and may inhibit P-gp. Methadone is associated with an increased risk for QT prolongation and torsade de pointes (TdP), especially at higher doses (more than 200 mg/day but averaging approximately 400 mg/day in adult patients). Mifepristone use is also associated with QT prolongation; to minimize this risk, the lowest effective dose of mifepristone should always be used. Use of these drugs together may increase the risk for QT prolongation. Due to the slow elimination of mifepristone from the body, such interactions may be observed for a prolonged period after mifepristone administration.
    Metronidazole: (Major) Concomitant use of metronidazole and mifepristone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Midazolam: (Major) Midazolam should be used with mifepristone only with caution, close monitoring, and consideration of appropriate midazolam dosage reduction. CNS depression, impaired motor and/or cognitive performance may occur due to increased midazolam exposure. Mifepristone inhibits CYP3A4 when it is used chronically in the treatment of hormonal conditions, such as Cushing's disease. Coadministration of mifepristone may lead to a significant increase in serum concentrations of drugs that are CYP3A4 substrates like midazolam. Due to the slow elimination of mifepristone from the body, such interactions may be observed for a prolonged period after mifepristone administration.
    Midostaurin: (Major) The concomitant use of midostaurin and mifepristone may lead to additive QT interval prolongation. If these drugs are used together, consider electrocardiogram monitoring. Use the lowest effective dose of mifepristone to minimize the risk of QT prolongation. In clinical trials, QT prolongation has been reported in patients who received midostaurin as single-agent therapy or in combination with cytarabine and daunorubicin. Mifepristone has been associated with dose-dependent prolongation of the QT interval.
    Mirtazapine: (Moderate) There may be an increased risk for QT prolongation and torsade de pointes (TdP) during concurrent use of mirtazapine and mifepristone (RU-486). Coadminister with caution. Mifepristone has been associated with dose-dependent prolongation of the QT interval. To minimize the risk of QT prolongation, the lowest effective dose of mifepristone should always be used. Cases of QT prolongation, TdP, ventricular tachycardia, and sudden death have been reported during postmarketing use of mirtazapine, primarily following overdose or in patients with other risk factors for QT prolongation, including concomitant use of other medications associated with QT prolongation.
    Mitotane: (Major) Avoid the concomitant use of mitotane with mifepristone due to duplication of pharmacodynamic effects and the potential for serious adrenalcortical insufficiency. The safe and effective use of these drugs together has not been established. Additionally, mitotane is a strong CYP3A4 inducer, and coadministration would be expected to decrease plasma concentrations of mifepristone. Avoid co-administration of mifepristone and CYP3A inducers such as mitotane. Use of mifepristone with CYP3A inducers has not been studied.
    Moxifloxacin: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), concurrent use of mifepristone and moxifloxacin should be avoided if possible. Mifepristone has been associated with dose-dependent prolongation of the QT interval. There is no experience with high exposure or concomitant use with other QT prolonging drugs. To minimize the risk of QT prolongation, the lowest effective dose should always be used. Prolongation of the QT interval has been reported with administration of moxifloxacin. Postmarketing surveillance has identified very rare cases of ventricular arrhythmias including TdP, usually in patients with severe underlying proarrhythmic conditions. The likelihood of QT prolongation may increase with increasing concentrations of moxifloxacin, therefore the recommended dose or infusion rate should not be exceeded.
    Nabumetone: (Moderate) Mifepristone significantly increased exposure of drugs metabolized by CYP2C8/2C9 in interaction studies. Therefore, when mifepristone is used chronically, as in the treatment of Cushing's syndrome, use caution with coadministered CYP2C8/2C9 substrates, including the NSAIDs. Use the lowest doses of the substrate and patients should be monitored closely for adverse reactions.
    Naloxegol: (Contraindicated) Concomitant use of naloxegol with chronic mifepristone therapy is contraindicated. Naloxegol is metabolized primarily by CYP3A. Strong CYP3A4 inhibitors, such as mifepristone, can significantly increase exposure to naloxegol which may precipitate opioid withdrawal symptoms such as hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning. The clinical significance of this interaction when mifepristone is used for pregnancy termination is not established.
    Nanoparticle Albumin-Bound Paclitaxel: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with mifepristone is necessary due to the risk of increased plasma concentrations of paclitaxel. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown. Nab-paclitaxel is a CYP3A4 and CYP2C8 substrate. Mifepristone is a strong CYP3A4 inhibitor and a moderate inhibitor of CYP2C8. In vitro, coadministration with both strong and moderate CYP3A4 inhibitors increased paclitaxel exposure; however, the concentrations used exceeded those found in vivo following normal therapeutic doses. The pharmacokinetics of paclitaxel may also be altered in vivo as a result of interactions with CYP3A4 inhibitors.
    Naproxen: (Moderate) Mifepristone significantly increased exposure of drugs metabolized by CYP2C8/2C9 in interaction studies. Therefore, when mifepristone is used chronically, as in the treatment of Cushing's syndrome, use caution with coadministered CYP2C8/2C9 substrates, including the NSAIDs. Use the lowest doses of the substrate and patients should be monitored closely for adverse reactions.
    Naproxen; Pseudoephedrine: (Moderate) Mifepristone significantly increased exposure of drugs metabolized by CYP2C8/2C9 in interaction studies. Therefore, when mifepristone is used chronically, as in the treatment of Cushing's syndrome, use caution with coadministered CYP2C8/2C9 substrates, including the NSAIDs. Use the lowest doses of the substrate and patients should be monitored closely for adverse reactions.
    Naproxen; Sumatriptan: (Moderate) Mifepristone significantly increased exposure of drugs metabolized by CYP2C8/2C9 in interaction studies. Therefore, when mifepristone is used chronically, as in the treatment of Cushing's syndrome, use caution with coadministered CYP2C8/2C9 substrates, including the NSAIDs. Use the lowest doses of the substrate and patients should be monitored closely for adverse reactions.
    Nefazodone: (Major) Caution is advised when administering nefazodone with mifepristone because increased serum concentrations of either drug may occur. When mifepristone is used in the treatment of Cushing's syndrome, coadministration with nefazodone should be done only when necessary, and in such cases the dose of mifepristone should be limited to a maximum dose of 900 mg per day. In a patient already receiving nefazodone, initiate mifepristone at a dose of 300 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with nefazodone is initiated in a patient already receiving mifepristone 300 mg, dosage adjustments are not required. If therapy with nefazodone is initiated in a patient already receiving mifepristone 600 mg, reduce dose of mifepristone to 300 mg and titrate to a maximum of 600 mg if clinically indicated. If therapy with nefazodone is initiated in a patient already receiving 900 mg, reduce dose of mifepristone to 600 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with nefazodone is initiated in a patient already receiving 1,200 mg, reduce the mifepristone dose to 900 mg. Both mifepristone and nefazodone are substrates and strong inhibitors of CYP3A4.
    Nelfinavir: (Major) Caution is advised when administering nelfinavir with mifepristone because increased serum concentrations of either drug may occur. When mifepristone is used in the treatment of Cushing's syndrome, coadministration with nelfinavir should be done only when necessary, and in such cases the dose of mifepristone should be limited to a maximum dose of 900 mg per day. In a patient already receiving nelfinavir, initiate mifepristone at a dose of 300 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with nelfinavir is initiated in a patient already receiving mifepristone 300 mg, dosage adjustments are not required. If therapy with nelfinavir is initiated in a patient already receiving mifepristone 600 mg, reduce dose of mifepristone to 300 mg and titrate to a maximum of 600 mg if clinically indicated. If therapy with nelfinavir is initiated in a patient already receiving 900 mg, reduce dose of mifepristone to 600 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with nelfinavir is initiated in a patient already receiving 1,200 mg, reduce the mifepristone dose to 900 mg. Both mifepristone and nelfinavir are substrates and strong inhibitors of CYP3A4.
    Neratinib: (Major) Avoid concomitant use of mifepristone with neratinib due to an increased risk of neratinib-related toxicity. Neratinib is a CYP3A4 substrate and mifepristone is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased neratinib exposure by 381%; concomitant use with other strong inhibitors of CYP3A4 may also increase neratinib concentrations. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
    Niacin; Simvastatin: (Contraindicated) When mifepristone is used in the treatment of Cushing's syndrome, coadministration is contraindicated based on studies demonstrating significant simvastatin exposure increases which may lead to an increased risk of myopathy and rhabdomyolysis. Consider interruption of simvastatin therapy during use of mifepristone for pregnancy termination. Due to the slow elimination of mifepristone from the body, such interactions may be observed for a prolonged period after mifepristone administration. Mifepristone is a strong CYP3A4 inhibitor; simvastatin is a sensitive CYP3A4 substrate. Coadministration of mifepristone and simvastatin increased simvastatin and simvastatin acid exposure by 10.4-fold and 15.7-fold, respectively, in drug interaction studies.
    Nicardipine: (Moderate) Monitor blood pressure and heart rate if coadministration of nicardipine with mifepristone is necessary. Concurrent use may result in elevated nicardipine concentrations. Nicardipine is a CYP3A4 substrate and mifepristone is a strong CYP3A4 inhibitor.
    Nifedipine: (Moderate) Monitor blood pressure and heart rate if coadministration of nifedipine with mifepristone is necessary. Concurrent use may result in elevated nifedipine concentrations. Nifedipine is a CYP3A4 substrate and mifepristone is a strong CYP3A4 inhibitor.
    Nilotinib: (Major) Avoid the concomitant use of nilotinib and mifepristone; significant prolongation of the QT interval may occur. Sudden death and QT interval prolongation have occurred in patients who received nilotinib therapy. Mifepristone has been associated with dose-dependent prolongation of the QT interval. To minimize the risk of QT prolongation, the lowest effective dose of mifepristone should always be used. If coadministration is required, monitor closely for prolongation of the QT interval and reduce the nilotinib dose to 300 mg once daily in adult patients with resistant or intolerant Ph+ CML or to 200 mg once daily in adult patients with newly diagnosed Ph+ CML. If mifepristone is discontinued, a washout period should be allowed before adjusting the nilotinib dosage upward to the indicated dose. Nilotinib is a substrate of CYP3A4 and mifepristone is a strong inhibitor of CYP3A4.
    Nimodipine: (Moderate) Monitor blood pressure and heart rate if coadministration of nimodipine with mifepristone is necessary. Concurrent use may result in elevated nimodipine concentrations. Nimodipine is a CYP3A4 substrate and mifepristone is a strong CYP3A4 inhibitor.
    Nintedanib: (Moderate) Dual inhibitors of P-glycoprotein (P-gp) and CYP3A4, such as mifepristone, are expected to increase the exposure and clinical effect of nintedanib. Due to the slow elimination of mifepristone from the body, such interactions may be observed for a prolonged period after mifepristone administration. If use together is necessary, closely monitor for increased nintedanib side effects including gastrointestinal toxicity (nausea, vomiting, diarrhea, abdominal pain, loss of appetite), headache, elevated liver enzymes, and hypertension. A dose reduction, interruption of therapy, or discontinuation of nintedanib therapy may be necessary. Mifepristone is a moderate inhibitor of P-gp and an inhibitor of CYP3A4; nintedanib is a P-gp substrate and a minor CYP3A4 substrate. In drug interactions studies, administration of nintedanib with a dual P-gp and CYP3A4 inhibitor increased nintedanib AUC by 60%.
    Nisoldipine: (Major) Avoid coadministration of nisoldipine with mifepristone due to increased plasma concentrations of nisoldipine. If coadministration is unavoidable, monitor blood pressure closely during concurrent use of these medications. Nisoldipine is a CYP3A4 substrate and mifepristone is a CYP3A4 inhibitor.
    Nonsteroidal antiinflammatory drugs: (Moderate) Mifepristone significantly increased exposure of drugs metabolized by CYP2C8/2C9 in interaction studies. Therefore, when mifepristone is used chronically, as in the treatment of Cushing's syndrome, use caution with coadministered CYP2C8/2C9 substrates, including the NSAIDs. Use the lowest doses of the substrate and patients should be monitored closely for adverse reactions.
    Norfloxacin: (Moderate) Due to a possible risk for QT prolongation and torsade de pointes (TdP), mifepristone and norfloxacin should be used together cautiously. Mifepristone has been associated with dose-dependent prolongation of the QT interval. There is no experience with high exposure or concomitant use with other QT prolonging drugs. To minimize the risk of QT prolongation, the lowest effective dose should always be used. Drugs with a possible risk for QT prolongation and torsades de pointes that should be used cautiously with mifepristone include norfloxacin.
    Nortriptyline: (Minor) Due to a possible risk for QT prolongation and torsade de pointes (TdP), mifepristone and tricyclic antidepressants should be used together cautiously. Mifepristone has been associated with dose-dependent prolongation of the QT interval. There is no experience with high exposure or concomitant use with other QT prolonging drugs. To minimize the risk of QT prolongation, the lowest effective dose should always be used. Drugs with a possible risk for QT prolongation and torsades de pointes that should be used cautiously with mifepristone include tricyclic antidepressants.
    Octreotide: (Moderate) Due to a possible risk for QT prolongation and torsade de pointes (TdP), mifepristone and octreotide should be used together cautiously. Mifepristone has been associated with dose-dependent prolongation of the QT interval. There is no experience with high exposure or concomitant use with other QT prolonging drugs. To minimize the risk of QT prolongation, the lowest effective dose should always be used. Drugs with a possible risk for QT prolongation and torsades de pointes that should be used cautiously with mifepristone include octreotide.
    Ofloxacin: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), concurrent use of mifepristone and ofloxacin should be avoided if possible. Mifepristone has been associated with dose-dependent prolongation of the QT interval. There is no experience with high exposure or concomitant use with other QT prolonging drugs. To minimize the risk of QT prolongation, the lowest effective dose should always be used. Some quinolones, including ofloxacin, have been associated with QT prolongation and infrequent cases of arrhythmia. Postmarketing surveillance for ofloxacin has identified very rare cases of TdP.
    Olanzapine: (Moderate) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering olanzapine with mifepristone. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances. Mifepristone has also been associated with dose-dependent prolongation of the QT interval. There is no experience with high exposure or concomitant use with other QT prolonging drugs. To minimize the risk of QT prolongation, the lowest effective dose should always be used.
    Olaparib: (Major) Avoid coadministration of olaparib with mifepristone due to the risk of increased olaparib-related adverse reactions. If concomitant use is unavoidable, reduce the dose of olaparib to 100 mg twice daily; the original dose may be resumed 3 to 5 elimination half-lives after mifepristone is discontinued. Olaparib is a CYP3A substrate and mifepristone is a strong CYP3A4 inhibitor; concomitant use may increase olaparib exposure. Coadministration with another strong CYP3A inhibitor increased the olaparib Cmax by 42% and the AUC by 170%. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
    Oliceridine: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and mifepristone is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and mifepristone may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If mifepristone is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP3A4 substrate and mifepristone is a strong CYP3A4 inhibitor.
    Ombitasvir; Paritaprevir; Ritonavir: (Major) Caution is advised when administering ritonavir with mifepristone because increased serum concentrations of either drug may occur. When mifepristone is used in the treatment of Cushing's syndrome, coadministration with ritonavir should be done only when necessary, and in such cases the dose of mifepristone should be limited to a maximum dose of 900 mg per day. In a patient already receiving ritonavir, initiate mifepristone at a dose of 300 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with ritonavir is initiated in a patient already receiving mifepristone 300 mg, dosage adjustments are not required. If therapy with ritonavir is initiated in a patient already receiving mifepristone 600 mg, reduce dose of mifepristone to 300 mg and titrate to a maximum of 600 mg if clinically indicated. If therapy with ritonavir is initiated in a patient already receiving 900 mg, reduce dose of mifepristone to 600 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with ritonavir is initiated in a patient already receiving 1,200 mg, reduce the mifepristone dose to 900 mg. Both mifepristone and ritonavir are substrates and strong inhibitors of CYP3A4. (Major) Elevated ombitasvir concentrations may result if mifepristone is coadministered chronically. If these drugs must be used together, closely monitor the patient for antiviral-related adverse events. Because ombitasvir is used in drug regimens that may reduce the clearance of mifepristone and increase the risk for QT prolongation, dosage reduction of mifepristone is necessary with certain medications. The response to mifepristone, when used chronically for hormonal conditions like Cushing's syndrome, requires careful monitoring. Consult the mifepristone package insert/product labeling for appropriate dose reduction. Mifepristone is a CYP3A4 inhibitor and substrate and may be a P-glycoprotein (P-gp) inhibitor. Ombitasvir is a P-gp substrate. Inhibition of P-gp may increase the plasma concentrations of ombitasvir. (Major) Elevated paritaprevir concentrations may result if mifepristone is coadministered chronically. If these drugs must be used together, closely monitor the patient for antiviral-related adverse events. Because paritaprevir is used in drug regimens that may reduce the clearance of mifepristone and increase the risk for QT prolongation, dosage reduction of mifepristone is necessary with certain medications. The response to mifepristone, when used chronically for hormonal conditions like Cushing's syndrome, requires careful monitoring. Consult the mifepristone package insert/product labeling for appropriate dose reduction. Mifepristone is a CYP3A4 inhibitor and may inhibit P-glycoprotein (P-gp). Paritaprevir is a CYP3A4 and P-gp substrate.
    Ondansetron: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), mifepristone and ondansetron should be used together cautiously. Mifepristone has been associated with dose-dependent prolongation of the QT interval. There is no experience with high exposure or concomitant use with other QT prolonging drugs. To minimize the risk of QT prolongation, the lowest effective dose should always be used. Ondansetron has been associated with QT prolongation and postmarketing reports of TdP. Among 42 patients receiving a 4 mg bolus dose of intravenous ondansetron for the treatment of postoperative nausea and vomiting, the mean maximal QTc interval prolongation was 20 +/- 13 msec at the third minute after antiemetic administration (p < 0.0001). If ondansetron and another drug that prolongs the QT interval must be coadministered, ECG monitoring is recommended.
    Oral Contraceptives: (Contraindicated) Mifepristone is a progesterone-receptor antagonist and will interfere with the effectiveness of hormonal contraceptives. Therefore, non-hormonal contraceptive methods should be used in Cushing's patients taking mifepristone.
    Oritavancin: (Moderate) Mifepristone is metabolized by CYP3A4; oritavancin is a weak CYP3A4 inducer. Plasma concentrations and efficacy of mifepristone may be reduced if these drugs are administered concurrently. Specific drug interactions with mifepristone have not been studied; it is not known if lowered mifepristone serum concentrations would lead to therapeutic failures.
    Osilodrostat: (Major) Avoid coadministration of mifepristone with osilodrostat due to the potential for additive QT prolongation. Mifepristone is associated with dose-related prolongation of the QT interval. Osilodrostat is associated with dose-dependent QT prolongation.
    Osimertinib: (Major) Avoid coadministration of mifepristone with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes. To minimize the risk of QT prolongation, the lowest effective dose of mifepristone should always be used. An interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Mifepristone has also been associated with dose-dependent prolongation of the QT interval.
    Oxaliplatin: (Major) Avoid coadministration of mifepristone with oxaliplatin due to the risk of QT prolongation. Mifepristone is associated with dose-related prolongation of the QT interval. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have also been reported with oxaliplatin use in postmarketing experience.
    Oxaprozin: (Moderate) Mifepristone significantly increased exposure of drugs metabolized by CYP2C8/2C9 in interaction studies. Therefore, when mifepristone is used chronically, as in the treatment of Cushing's syndrome, use caution with coadministered CYP2C8/2C9 substrates, including the NSAIDs. Use the lowest doses of the substrate and patients should be monitored closely for adverse reactions.
    Oxybutynin: (Moderate) Oxybutynin is metabolized by CYP3A4. Inhibitors of the CYP3A4 enzyme, such as mifepristone, may increase the serum concentrations of oxybutynin. The manufacturer recommends caution when oxybutynin is co-administered with CYP3A4 inhibitors.
    Oxycodone: (Moderate) Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression and sedation if concurrent use of mifepristone is necessary. If mifepristone is discontinued, consider increasing the oxycodone dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oxycodone is a CYP3A4 substrate, and coadministration with a strong CYP3A4 inhibitor like mifepristone can increase oxycodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of oxycodone. If mifepristone is discontinued, oxycodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to oxycodone. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
    Ozanimod: (Major) In general, do not initiate ozanimod in patients taking mifepristone due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Mifepristone is associated with dose-related prolongation of the QT interval.
    Palbociclib: (Major) Avoid coadministration of chronic mifepristone with palbociclib due to increased palbociclib exposure. If concomitant use is unavoidable, reduce the dose of palbociclib to 75 mg once daily. If mifepristone is discontinued, wait 3 to 5 half-lives of mifepristone and then increase palbociclib to its original dose. Palbociclib is a CYP3A substrate and mifepristone is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A inhibitor increased palbociclib exposure after a single dose by approximately 87%. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
    Paliperidone: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), concurrent use of mifepristone and paliperidone should be avoided if possible. Mifepristone has been associated with dose-dependent prolongation of the QT interval. There is no experience with high exposure or concomitant use with other QT prolonging drugs. To minimize the risk of QT prolongation, the lowest effective dose should always be used. Paliperidone has been associated with QT prolongation; TdP and ventricular fibrillation have been reported in the setting of overdose. According to the manufacturer, since paliperidone may prolong the QT interval, it should be avoided in combination with other agents also known to have this effect. However, if coadministration is necessary and the patient has known risk factors for cardiac disease or arrhythmias, close monitoring is essential.
    Panobinostat: (Major) The co-administration of panobinostat with mifepristone is not recommended; QT prolongation has been reported with both agents. Mifepristone is a CYP3A4 inhibitor and panobinostat is a CYP3A4 substrate. The panobinostat Cmax and AUC (0-48hr) values were increased by 62% and 73%, respectively, in patients with advanced cancer who received a single 20 mg-dose of panobinostat after taking 14 days of a strong CYP3A4 inhibitor. Although an initial panobinostat dose reduction is recommended in patients taking concomitant strong CYP3A4 inhibitors, no dose recommendations with mild or moderate CYP3A4 inhibitors are provided by the manufacturer. If concomitant use of mifepristone and panobinostat cannot be avoided, closely monitor electrocardiograms and for signs and symptoms of panobinostat toxicity such as cardiac arrhythmias, diarrhea, bleeding, infection, and hepatotoxicity. Hold panobinostat if the QTcF increases to >= 480 milliseconds during therapy; permanently discontinue if QT prolongation does not resolve.
    Pasireotide: (Major) Cautious use of pasireotide and mifepristone is needed, as coadministration may have additive effects on the prolongation of the QT interval. Mifepristone has been associated with dose-dependent prolongation of the QT interval. There is no experience with high exposure or concomitant use with other QT prolonging drugs. To minimize the risk of QT prolongation, the lowest effective dose should always be used.
    Pazopanib: (Major) Coadministration of pazopanib and other drugs that prolong the QT interval, such as mifepristone, is not advised; pazopanib has been reported to prolong the QT interval. If pazopanib and the other drug must be continued, closely monitor the patient for QT interval prolongation. Mifepristone has been associated with dose-dependent prolongation of the QT interval. There is no experience with high exposure or concomitant use with other QT prolonging drugs. To minimize the risk of QT prolongation, the lowest effective dose should always be used. Although specific drug interactions with mifepristone have not been studied, the use of mifepristone with CYP3A inhibitors may result in increased mifepristone concentrations and an increased risk of QT prolongation.
    Pemigatinib: (Major) Avoid coadministration of pemigatinib and mifepristone due to the risk of increased pemigatinib exposure which may increase the risk of adverse reactions. If coadministration is unavoidable, reduce the dose of pemigatinib to 9 mg PO once daily if original dose was 13.5 mg per day and to 4.5 mg PO once daily if original dose was 9 mg per day. If mifepristone is discontinued, resume the original pemigatinib dose after 3 elimination half-lives of mifepristone. Pemigatinib is a CYP3A4 substrate and mifepristone is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased pemigatinib exposure by 88%. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
    Pentamidine: (Major) Mifepristone has been associated with dose-dependent prolongation of the QT interval. There is no experience with high exposure or concomitant use with other QT prolonging drugs. To minimize the risk of QT prolongation, the lowest effective dose should always be used. Drugs with a possible risk for QT prolongation and torsades de pointes that should be used cautiously and with close monitoring with mifepristone include pentamidine. Systemic pentamidine is associated with QT prolongation.
    Pentosan: (Major) When mifepristone is used for the termination of pregnancy, concurrent use of anticoagulants is contraindicated due to the increased risk of serious bleeding. When mifepristone is used chronically for hormonal conditions, such as Cushing's disease, the concurrent use of some anticoagulants should be approached with caution, but specific interactions with pentosan are not expected.
    Perindopril; Amlodipine: (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with mifepristone is necessary; adjust the dose of amlodipine as clinically appropriate. Mifepristone is a strong CYP3A inhibitor and amlodipine is a CYP3A substrate. Coadministration with a moderate CYP3A4 inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. Strong CYP3A4 inhibitors may increase the plasma concentrations of amlodipine to a greater extent.
    Perphenazine: (Minor) Due to a possible risk for QT prolongation and torsade de pointes (TdP), mifepristone and perphenazine should be used together cautiously. Mifepristone has been associated with dose-dependent prolongation of the QT interval. There is no experience with high exposure or concomitant use with other QT prolonging drugs. To minimize the risk of QT prolongation, the lowest effective dose should always be used. Drugs with a possible risk for QT prolongation and torsades de pointes that should be used cautiously with mifepristone include perphenazine.
    Perphenazine; Amitriptyline: (Minor) Due to a possible risk for QT prolongation and torsade de pointes (TdP), mifepristone and perphenazine should be used together cautiously. Mifepristone has been associated with dose-dependent prolongation of the QT interval. There is no experience with high exposure or concomitant use with other QT prolonging drugs. To minimize the risk of QT prolongation, the lowest effective dose should always be used. Drugs with a possible risk for QT prolongation and torsades de pointes that should be used cautiously with mifepristone include perphenazine. (Minor) Due to a possible risk for QT prolongation and torsade de pointes (TdP), mifepristone and tricyclic antidepressants should be used together cautiously. Mifepristone has been associated with dose-dependent prolongation of the QT interval. There is no experience with high exposure or concomitant use with other QT prolonging drugs. To minimize the risk of QT prolongation, the lowest effective dose should always be used. Drugs with a possible risk for QT prolongation and torsades de pointes that should be used cautiously with mifepristone include tricyclic antidepressants.
    Pexidartinib: (Major) Avoid coadministration of pexidartinib with mifepristone as concurrent use may increase pexidartinib exposure. If concurrent use cannot be avoided, reduce the dose of pexidartinib. If mifepristone is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of mifepristone. Dose adjustments are as follows: 800 mg/day or 600 mg/day of pexidartinib, reduce to 200 mg twice daily; 400 mg/day of pexidartinib, reduce to 200 mg once daily. Pexidartinib is a CYP3A4 substrate; mifepristone is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased pexidartinib exposure by 70%.
    Phenobarbital: (Major) Avoid the use of mifepristone and potent CYP3A inducers such as phenobarbital. It is not known if lowered mifepristone serum levels would lead to reduced response or therapeutic failure. If use together is medically necessary, monitor the patient closely to ensure the proper therapeutic response is obtained.
    Phenytoin: (Major) Avoid coadministration of mifepristone and CYP3A inducers such as phenytoin. It is not known if lowered mifepristone serum levels would lead to reduced response or therapeutic failure. Mifepristone, when used chronically for hormonal conditions such as Cushing's disease, is a CYP2C9 inhibitor and is likely to increase plasma concentrations of phenytoin, a sensitive CYP2C9 substrate. Due to the slow elimination of mifepristone from the body, any drug interactions that occur may be prolonged. If use together is medically necessary, monitor the patient closely to ensure the proper therapeutic response is obtained to both medications. Monitor for signs/symptoms of phenytoin toxicity.
    Pimavanserin: (Major) Pimavanserin may cause QT prolongation and should generally be avoided in patients receiving other medications known to prolong the QT interval, such as mifepristone, due to a potential increased risk of QT prolongation. In addition, because pimavanserin is primarily metabolized by CYP3A4 and CYP3A5, the manufacturer recommends that the pimavanserin dose be reduced to 10 mg/day PO in patients receiving strong inhibitors of CYP3A4 such as mifepristone. If these agents are used in combination, the patient should be carefully monitored for pimavanserin-related adverse reactions, including nausea, vomiting, confusion, loss of balance or coordination, and QT prolongation.
    Pimozide: (Contraindicated) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Because of the potential for TdP, use of mifepristone with pimozide is contraindicated.
    Piroxicam: (Moderate) Mifepristone significantly increased exposure of drugs metabolized by CYP2C8/2C9 in interaction studies. Therefore, when mifepristone is used chronically, as in the treatment of Cushing's syndrome, use caution with coadministered CYP2C8/2C9 substrates, including the NSAIDs. Use the lowest doses of the substrate and patients should be monitored closely for adverse reactions.
    Pitolisant: (Major) Avoid coadministration of pitolisant with mifepristone as concurrent use may increase the risk of QT prolongation. Pitolisant prolongs the QT interval. Mifepristone is associated with dose-related prolongation of the QT interval.
    Polatuzumab Vedotin: (Moderate) Monitor for increased polatuzumab vedotin toxicity during coadministration of mifepristone due to the risk of elevated exposure to the cytotoxic component of polatuzumab vedotin, MMAE. MMAE is metabolized by CYP3A4; mifepristone is a strong CYP3A4 inhibitor. Strong CYP3A4 inhibitors are predicted to increase the exposure of MMAE by 45%. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
    Ponatinib: (Major) Avoid coadministration of ponatinib and mifepristone due to the potential for increased ponatinib exposure. If concurrent use cannot be avoided, reduce the ponatinib dose to the next lower dose level (45 mg to 30 mg; 30 mg to 15 mg; 15 mg to 10 mg). If the patient is taking ponatinib 10 mg once daily prior to concurrent use, avoid the use of mifepristone and consider alternative therapy. After mifepristone has been discontinued for 3 to 5 half-lives, resume the dose of ponatinib that was tolerated prior to starting mifepristone. Ponatinib is a CYP3A4 substrate; mifepristone is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the ponatinib AUC by 78%. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
    Ponesimod: (Major) In general, do not initiate ponesimod in patients taking mifepristone due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ponesimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ponesimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Mifepristone is associated with dose-related prolongation of the QT interval.
    Posaconazole: (Contraindicated) Coadministration of posaconazole and mifepristone is contraindicated due to the risk of additive QT prolongation and life threatening arrhythmias such as torsades de pointes (TdP); the exposure of both drugs may also be increased. If concomitant use of mifepristone is necessary for the treatment of Cushing's syndrome in a patient already receiving posaconazole, initiate mifepristone at a dose of 300 mg and titrate to a maximum of 900 mg daily if clinically indicated. If therapy with posaconazole is initiated in a patient already receiving mifepristone 300 mg, dosage adjustments are not required. If therapy with posaconazole is initiated in a patient already receiving mifepristone 600 mg, reduce dose of mifepristone to 300 mg and titrate to a maximum of 600 mg if clinically indicated. If therapy with posaconazole is initiated in a patient already receiving 900 mg, reduce dose of mifepristone to 600 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with posaconazole is initiated in a patient already receiving 1,200 mg, reduce the mifepristone dose to 900 mg/day. Both mifepristone and posaconazole are substrates and strong inhibitors of CYP3A4 that are associated with QT prolongation.
    Pralsetinib: (Major) Avoid coadministration of mifepristone with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is unavoidable, reduce the dose of pralsetinib to 200 mg once daily for patients taking a daily dose of 400 mg or 300 mg, and to 100 mg once daily for patients taking a daily dose of 200 mg. After mifepristone has been discontinued for 3 to 5 elimination half-lives, resume the pralsetinib dose taken prior to initiating mifepristone. Pralsetinib is a CYP3A and P-glycoprotein (P-gp) substrate and mifepristone is a combined P-gp and strong CYP3A inhibitor. Coadministration with another combined P-gp and strong CYP3A inhibitor increased the AUC of pralsetinib by 251%. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
    Primaquine: (Major) Avoid use together if possible; consider alternative therapies to primaquine. Due to the potential for QT interval prolongation with primaquine, caution is advised with other drugs that prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with primaquine include mifepristone. Mifepristone, when used chronically for hormonal conditions, such as Cushing's syndrome, has been associated with QT prolongation. To limit the risk for QT prolongation, the lowest effective dose of mifepristone should be used. Closely monitor.
    Primidone: (Major) Avoid the use of mifepristone and potent CYP3A inducers such as primidone. It is not known if lowered mifepristone serum levels would lead to reduced response or therapeutic failure. If use together is medically necessary, monitor the patient closely to ensure the proper therapeutic response is obtained.
    Procainamide: (Major) Mifepristone should be used cautiously and with close monitoring with procainamide. Procainamide is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Mifepristone has been associated with dose-dependent prolongation of the QT interval. There is no experience with high exposure or concomitant use with other QT prolonging drugs. To minimize the risk of QT prolongation, the lowest effect dose should always be used.
    Prochlorperazine: (Minor) Due to a possible risk for QT prolongation and torsade de pointes (TdP), mifepristone and prochlorperazine should be used together cautiously. Mifepristone has been associated with dose-dependent prolongation of the QT interval. There is no experience with high exposure or concomitant use with other QT prolonging drugs. To minimize the risk of QT prolongation, the lowest effective dose should always be used. Drugs with a possible risk for QT prolongation and torsades de pointes that should be used cautiously with mifepristone include prochlorperazine.
    Progesterone: (Moderate) Use caution if coadministration of mifepristone with progesterone is necessary, as the systemic exposure of progesterone may be increased resulting in an increase in treatment-related adverse reactions. Mifepristone is a strong CYP3A4 inhibitor. Progesterone is metabolized primarily by hydroxylation via a CYP3A4. This interaction does not apply to vaginal preparations of progesterone (e.g., Crinone, Endometrin).
    Promethazine: (Moderate) Promethazine carries a possible risk of QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with promethazine include mifepristone.
    Promethazine; Dextromethorphan: (Moderate) Promethazine carries a possible risk of QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with promethazine include mifepristone.
    Promethazine; Phenylephrine: (Moderate) Promethazine carries a possible risk of QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with promethazine include mifepristone.
    Propafenone: (Major) Propafenone should be used cautiously and with close monitoring with mifepristone. Propafenone is a Class IC antiarrhythmic which increases the QT interval, but largely due to prolongation of the QRS interval. Mifepristone has been associated with dose-dependent prolongation of the QT interval. There is no experience with high exposure or concomitant use with other QT prolonging drugs. To minimize the risk of QT prolongation, the lowest effective dose should always be used.
    Protriptyline: (Minor) Due to a possible risk for QT prolongation and torsade de pointes (TdP), mifepristone and tricyclic antidepressants should be used together cautiously. Mifepristone has been associated with dose-dependent prolongation of the QT interval. There is no experience with high exposure or concomitant use with other QT prolonging drugs. To minimize the risk of QT prolongation, the lowest effective dose should always be used. Drugs with a possible risk for QT prolongation and torsades de pointes that should be used cautiously with mifepristone include tricyclic antidepressants.
    Quetiapine: (Major) Quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. According to the manufacturer, use of quetiapine should be avoided in combination with drugs known to increase the QT interval. Mifepristone has been associated with dose-dependent prolongation of the QT interval. There is no experience with high exposure or concomitant use with other QT prolonging drugs. To minimize the risk of QT prolongation, the lowest effect dose should always be used. In addition, the cytochrome P450 3A4 (CYP3A4) isoenzyme is involved in the metabolism of quetiapine. Mifepristone may increase plasma concentrations of quetiapine through CYP3A4 inhibition. The manufacturer of quetiapine recommends a reduced dosage during concurrent administration of CYP3A4 inhibitors.
    Quinidine: (Contraindicated) Use of quinidine with mifepristone is contraindicated when mifepristone is used chronically for hormonal conditions, such as in the treatment of Cushing's syndrome. Mifepristone, a CYP3A4 inhibitor, is likely to increase quinidine concentrations and adverse effects, since quinidine is a CYP3A4 substrate with a narrow therapeutic index. Increased quinidine concentrations are likely to cause proarrythmia and ECG changes, as well as symptoms of cinchonism. Both quinidine and mifepristone have been associated with QT prolongation and a risk for torsade de pointes (TdP). Due to the slow elimination of mifepristone from the body, such interactions may be observed for a prolonged period after mifepristone administration.
    Quinine: (Major) Concurrent use of quinine and mifepristone should generally be avoided due to an increased risk for elevated concentrations of either drug and an increased risk for QT prolongation and torsade de pointes (TdP). Consider alternative drug therapy if possible. Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Mifepristone has also been associated with dose-dependent prolongation of the QT interval. In addition, both drugs are inhibitors and substrates of CYP3A4; coadministration may result in increased concentration of both drugs. Monitor for quinine-related "cinchonism". Monitor for adrenal suppression from Mifepristone. To minimize the risk for QT prolongation, the lowest effective dose of mifepristone should be used.
    Ramelteon: (Moderate) Ramelteon should be administered with caution in subjects taking strong CYP3A4 inhibitors. Because ramelteon is partially metabolized via CYP3A4, an increase in exposure of ramelteon is expected. An increase in ramelteon AUC by approximately 84% and Cmax by 36% was noted when coadministered with a strong CYP3A4 inhibitor (ketoconazole). Similar increases were noted in M-II pharmacokinetics. Patients should be monitored for increased ramelteon side effects. Examples of CYP3A4 inhibitors include: chloramphenicol, conivaptan, cyclosporine, dalfopristin; quinupristin, delavirdine, diltiazem, erythromycin, ethinyl estradiol, imatinib, STI-571, itraconazole, systemic miconazole, mifepristone, troleandomycin, verapamil, voriconazole, and zafirlukast. This list is not inclusive of all CYP3A4 inhibitors. Imatinib, voriconazole, and zafirlukast are also CYP2C9 inhibitors, and when administered with ramelteon may result in multiple hepatic enzyme inhibition interactions, although the significance of these interactions has not been studied. The patient should be monitored closely for ramelteon-associated toxicity.
    Ranolazine: (Major) Avoid use together if possible. Both drugs may prolong the QT interval and may increase the risk for arrhythmia. If use together is necessary, limit the ranolazine dosage to 500 mg PO twice daily. Monitor for ranolazine-related adverse reactions such as dizziness, headache, constipation, and nausea. Limit the mifepristone to the lowest effective dose to reduce QT prolongation risk. Ranolazine is metabolized mainly by CYP3A4 and to an extent by P-glycoprotein (P-gp) and mifepristone is known to inhibit CYP3A4 and may also inhibit P-glycoprotein (P-gp); use together is expected to increase ranolazine concentrations. Due to the slow elimination of mifepristone from the body, drug interactions that occur may be prolonged.
    Red Yeast Rice: (Major) Advise patients not to take red yeast rice with mifepristone. Certain red yeast rice dietary supplement products contain lovastatin. Mifepristone is a CYP3A4 inhibitor and is contraindicated with lovastatin due to the expected increase in serum concentrations of lovastatin and the potential for myopathy, rhabdomyolysis or other serious HMG-CoA reductase inhibitor effects. Due to the slow elimination of mifepristone from the body, any interactions that do occur may be prolonged.
    Regorafenib: (Major) Avoid coadministration of regorafenib with mifepristone due to increased plasma concentrations of regorafenib and decreased plasma concentrations of the active metabolites M-2 and M-5, which may lead to increased toxicity. Regorafenib is a CYP3A4 substrate and mifepristone is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased regorafenib exposure by 33% and decreased exposure of M-2 and M-5 by 93% each. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
    Relugolix: (Major) Avoid use of mifepristone with QT interval prolonging drugs. Mifepristone is associated with dose-related prolongation of the QT interval. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval. Concomitant use may also increase relugolix exposure and the risk of other relugolix-related adverse effects. If concomitant use is unavoidable, administer mifepristone at least 6 hours after relugolix and monitor for adverse reactions. Alternatively, relugolix therapy may be interrupted for up to 14 days if a short course of mifepristone is required; if treatment is interrupted for more than 7 days, resume relugolix with a 360 mg loading dose followed by 120 mg once daily. Relugolix is a P-glycoprotein (P-gp) substrate and mifepristone is a P-gp inhibitor.
    Relugolix; Estradiol; Norethindrone acetate: (Major) Avoid use of mifepristone with QT interval prolonging drugs. Mifepristone is associated with dose-related prolongation of the QT interval. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval. Concomitant use may also increase relugolix exposure and the risk of other relugolix-related adverse effects. If concomitant use is unavoidable, administer mifepristone at least 6 hours after relugolix and monitor for adverse reactions. Alternatively, relugolix therapy may be interrupted for up to 14 days if a short course of mifepristone is required; if treatment is interrupted for more than 7 days, resume relugolix with a 360 mg loading dose followed by 120 mg once daily. Relugolix is a P-glycoprotein (P-gp) substrate and mifepristone is a P-gp inhibitor.
    Repaglinide: (Moderate) Repaglinide dose reductions and increased frequency of glucose monitoring may be required when mifepristone (for chronic conditions) is prescribed concurrently. When mifepristone is used chronically, such as with Cushing's syndrome, the lowest dose of repaglinide should be used that results in proper clinical response and tolerance. Monitor closely for hypoglycemia and adverse reactions. In some patients, a lower dose of repaglinide will be needed. Repaglinide is a CYP2C8 substrate. Mifepristone significantly increases exposure of drugs metabolized by CYP2C8, and can be expected to increase repaglinide exposure. Due to the slow elimination of mifepristone from the body, such interactions may be observed for a prolonged period after mifepristone administration.
    Retapamulin: (Moderate) Coadministration of retapamulin with strong CYP3A4 inhibitors, such as chronic mifepristone therapy, in patients younger than 24 months is not recommended. Systemic exposure of topically administered retapamulin may be higher in patients younger than 24 months than in patients 2 years and older. Retapamulin is a CYP3A4 substrate.
    Ribociclib: (Major) Avoid coadministration of mifepristone with ribociclib due to the risk of additive QT prolongation; the exposure of both drugs may also be increased. If concomitant use of mifepristone is necessary for the treatment of Cushing's syndrome in a patient already receiving ribociclib, initiate mifepristone at a dose of 300 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with ribociclib is initiated in a patient already receiving mifepristone 300 mg, dosage adjustments are not required. If therapy with ribociclib is initiated in a patient already receiving mifepristone 600 mg, reduce dose of mifepristone to 300 mg and titrate to a maximum of 600 mg if clinically indicated. If therapy with ribociclib is initiated in a patient already receiving 900 mg, reduce dose of mifepristone to 600 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with ribociclib is initiated in a patient already receiving 1,200 mg, reduce the mifepristone dose to 900 mg. Both mifepristone and ribociclib are substrates and strong inhibitors of CYP3A4 that are associated with QT prolongation.
    Ribociclib; Letrozole: (Major) Avoid coadministration of mifepristone with ribociclib due to the risk of additive QT prolongation; the exposure of both drugs may also be increased. If concomitant use of mifepristone is necessary for the treatment of Cushing's syndrome in a patient already receiving ribociclib, initiate mifepristone at a dose of 300 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with ribociclib is initiated in a patient already receiving mifepristone 300 mg, dosage adjustments are not required. If therapy with ribociclib is initiated in a patient already receiving mifepristone 600 mg, reduce dose of mifepristone to 300 mg and titrate to a maximum of 600 mg if clinically indicated. If therapy with ribociclib is initiated in a patient already receiving 900 mg, reduce dose of mifepristone to 600 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with ribociclib is initiated in a patient already receiving 1,200 mg, reduce the mifepristone dose to 900 mg. Both mifepristone and ribociclib are substrates and strong inhibitors of CYP3A4 that are associated with QT prolongation.
    Rifampin: (Major) When mifepristone is administered for the treatment of Cushing's syndrome, avoid coadministration of rifampin. When mifepristone is administered for pregnancy termination, follow-up assessment to verify that treatment has been successful is recommended in patients receiving rifampin. Coadministration may decrease mifepristone exposure reducing efficacy. Mifepristone is a CYP3A4 substrate; rifampin is a strong CYP3A4 inducer. The impact of CYP3A4 inducers on mifepristone efficacy is unknown.
    Rifapentine: (Major) When mifepristone is administered for the treatment of Cushing's syndrome, avoid coadministration of rifapentine. When mifepristone is administered for pregnancy termination, follow-up assessment to verify that treatment has been successful is recommended in patients receiving rifapentine. Coadministration may decrease mifepristone exposure reducing efficacy. Mifepristone is a CYP3A4 substrate; rifapentine is a strong CYP3A4 inducer. The impact of CYP3A4 inducers on mifepristone efficacy is unknown.
    Rilpivirine: (Major) Avoid use together if possible due to the risk of elevated rilpivirine exposure and a combined risk for QT prolongation. Consider alternatives to rilpivirine when coadministered with a drug with a known risk of QT prolongation and torsade de pointes (TdP), such as mifepristone when it is used for chronic hormonal conditions, such as Cushing's syndrome. Mifepristone is an inhibitor of CYP3A4; rilpivirine is a CYP3A4 substrate. Coadministration is likely to increase rilpivirine plasma concentrations. Monitor for rilpivirine-related side effects, including rash, mood changes or depression, fast, irregular heart rate, and hepatotoxicity. To minimize the risk of QT prolongation, the lowest effect dose of mifepristone should always be used.
    Rimegepant: (Major) Avoid coadministration of rimegepant with mifepristone; concurrent use may significantly increase rimegepant exposure. Rimegepant is a CYP3A4 and P-gp substrate; mifepristone is a strong CYP3A4 inhibitor and P-gp inhibitor. Coadministration of rimegepant with another strong CYP3A4 inhibitor increased rimegepant exposure by 4-fold.
    Ripretinib: (Moderate) Monitor patients more frequently for ripretinib-related adverse reactions if coadministered with mifepristone. Coadministration may increase the exposure of ripretinib and its active metabolite (DP-5439), which may increase the risk of adverse reactions. Ripretinib and DP-5439 are metabolized by CYP3A4 and mifepristone is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased ripretinib and DP-5439 exposure by 99%.
    Risperidone: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), mifepristone and risperidone should be used together cautiously. Mifepristone has been associated with dose-dependent prolongation of the QT interval. There is no experience with high exposure or concomitant use with other QT prolonging drugs. To minimize the risk of QT prolongation, the lowest effective dose should always be used. Risperidone has been associated with a possible risk for QT prolongation and TdP; however, data are currently lacking to establish causality in association with TdP. Reports of QT prolongation and TdP during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting. Since risperidone may prolong the QT interval, it should be used cautiously with other agents also known to have this effect, taking into account the patient's underlying disease state(s) and additional potential risk factors. If coadministration is chosen, and the patient has known risk factors for cardiac disease or arrhythmia, then the patient should be closely monitored clinically.
    Ritonavir: (Major) Caution is advised when administering ritonavir with mifepristone because increased serum concentrations of either drug may occur. When mifepristone is used in the treatment of Cushing's syndrome, coadministration with ritonavir should be done only when necessary, and in such cases the dose of mifepristone should be limited to a maximum dose of 900 mg per day. In a patient already receiving ritonavir, initiate mifepristone at a dose of 300 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with ritonavir is initiated in a patient already receiving mifepristone 300 mg, dosage adjustments are not required. If therapy with ritonavir is initiated in a patient already receiving mifepristone 600 mg, reduce dose of mifepristone to 300 mg and titrate to a maximum of 600 mg if clinically indicated. If therapy with ritonavir is initiated in a patient already receiving 900 mg, reduce dose of mifepristone to 600 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with ritonavir is initiated in a patient already receiving 1,200 mg, reduce the mifepristone dose to 900 mg. Both mifepristone and ritonavir are substrates and strong inhibitors of CYP3A4.
    Rivaroxaban: (Major) When mifepristone is used for the termination of pregnancy, concurrent use of anticoagulants is contraindicated due to the increased risk of serious bleeding. These drugs may be used together with caution when mifepristone is given chronically for other conditions, such as Cushing's syndrome. Increased serum concentrations of rivaroxaban are possible. Mifepristone is a CYP3A4 inhibitor and may inhibit P-glycoprotein (P-gp). Rivaroxaban is a substrate of CYP3A4/5 and the P-gp transporter. It is not clear if mifepristone exhibits a pharmacokinetic interaction with rivaroxaban. Patients should be monitored for bleeding and increased adverse effects of rivaroxaban. Coadministration in patients with renal impairment may result in increased exposure to rivaroxaban compared with patients with normal renal function. Different recommendations may apply to the use of mifepristone with rivaroxaban when the patient is also renally impaired. If active pathological bleeding occurs, rivaroxaban should be discontinued. Due to the long duration of action of mifepristone, any drug interaction that occurs may be prolonged.
    Rofecoxib: (Moderate) Mifepristone significantly increased exposure of drugs metabolized by CYP2C8/2C9 in interaction studies. Therefore, when mifepristone is used chronically, as in the treatment of Cushing's syndrome, use caution with coadministered CYP2C8/2C9 substrates, including the NSAIDs. Use the lowest doses of the substrate and patients should be monitored closely for adverse reactions.
    Romidepsin: (Major) Avoid use together if possible. Both romidepsin and mifepristone have been reported to prolong the QT interval. If romidepsin must be coadministered with another drug that prolongs the QT interval, appropriate cardiovascular monitoring precautions should be considered, such as the monitoring of electrolytes and ECGs at baseline and periodically during treatment. To minimize the risk of QT prolongation, the lowest effect dose of mifepristone should always be used when it is given chronically for hormonal conditions, such as Cushing's syndrome. In addition, romidepsin is a substrate for CYP3A4 and P-glycoprotein (P-gp). Mifepristone is a CYP3A4 inhibitor and may inhibit P-gp. Concurrent administration of romidepsin with an inhibitor of CYP3A4 and P-gp may cause an increase in systemic romidepsin concentrations. Monitor for toxicity related to increased romidepsin exposure, including hematologic and non-hematologic toxicity and follow the romidepsin dose modifications for toxicity as clinically indicated.
    Ruxolitinib: (Major) Reduce the ruxolitinib dosage during coadministration with mifepristone in patients with myelofibrosis (MF) or polycythemia vera (PV) as increased ruxolitinib exposure and toxicity may occur; no dose adjustments are necessary for patients with graft-versus-host disease. In MF patients, reduce the initial dose to 10 mg PO twice daily for platelet count of 100,000 cells/mm3 or more and 5 mg PO once daily for platelet count of 50,000 to 99,999 cells/mm3. In PV patients, reduce the initial dose to 5 mg PO twice daily. Avoid the use of mifepristone or interrupt ruxolitinib treatment during mifepristone use in MF or PV patients who are stable on a ruxolitinib dose of 5 mg PO once daily. In MF or PV patients stable on ruxolitinib dose of 10 mg PO twice daily or more, reduce dose by 50%; in patients stable on ruxolitinib dose of 5 mg PO twice daily, reduce ruxolitinib to 5 mg PO once daily. Additional dose modifications should be made with frequent monitoring of safety and efficacy. Ruxolitinib is a CYP3A4 substrate; mifepristone is a strong CYP3A4 inhibitor.
    Saquinavir: (Contraindicated) Coadministration of saquinavir and mifepristone is contraindicated due to the risk of additive QT prolongation and life-threatening arrhythmias such as torsade de pointes (TdP); the exposure of both drugs may also be increased. If concomitant use of mifepristone is necessary for the treatment of Cushing's syndrome in a patient already receiving saquinavir, initiate mifepristone at a dose of 300 mg and titrate to a maximum of 900 mg daily if clinically indicated. If therapy with saquinavir is initiated in a patient already receiving mifepristone 300 mg, dosage adjustments are not required. If therapy with saquinavir is initiated in a patient already receiving mifepristone 600 mg, reduce dose of mifepristone to 300 mg and titrate to a maximum of 600 mg if clinically indicated. If therapy with saquinavir is initiated in a patient already receiving 900 mg, reduce dose of mifepristone to 600 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with saquinavir is initiated in a patient already receiving 1,200 mg, reduce the mifepristone dose to 900 mg/day. Both mifepristone and saquinavir are substrates and strong inhibitors of CYP3A4 that are associated with QT prolongation.
    Saxagliptin: (Moderate) Monitor patients for hypoglycemia if saxagliptin and mifepristone are used together; dosage reduction of saxagliptin may be needed in some patients. In patients taking CYP3A substrates, the manufacturer of mifepristone recommends that the lowest dose of the CYP3A substrate that achieves the proper clinical response and tolerability be used. When potent CYP3A inhibitors are used, the initial dose of saxagliptin should be limited to 2.5 mg/day; mifepristone is a CYP3A inhibitor and has been noted to increase concentrations of CYP3A substrates. Due to the slow elimination of mifepristone from the body, such interactions may be observed for a prolonged period after mifepristone administration.
    Segesterone Acetate; Ethinyl Estradiol: (Contraindicated) Mifepristone is a progesterone-receptor antagonist and will interfere with the effectiveness of hormonal contraceptives. Therefore, non-hormonal contraceptive methods should be used in Cushing's patients taking mifepristone.
    Selpercatinib: (Major) Avoid coadministration of selpercatinib and mifepristone due to the risk of additive QT prolongation and increased selpercatinib exposure resulting in increased treatment-related adverse effects. If coadministration is unavoidable, reduce the dose of selpercatinib to 40 mg PO twice daily if original dose was 120 mg twice daily, and to 80 mg PO twice daily if original dose was 160 mg twice daily. Monitor ECGs for QT prolongation more frequently. If mifepristone is discontinued, resume the original selpercatinib dose after 3 to 5 elimination half-lives of mifepristone. Selpercatinib is a CYP3A4 substrate that has been associated with concentration-dependent QT prolongation; mifepristone is a strong CYP3A4 inhibitor that is associated with dose-related prolongation of the QT interval. Coadministration with another strong CYP3A4 inhibitor increased selpercatinib exposure by 133%. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
    Selumetinib: (Major) Avoid coadministration of selumetinib and mifepristone due to the risk of increased selumetinib exposure which may increase the risk of adverse reactions. If coadministration is unavoidable, reduce the dose of selumetinib to 20 mg/m2 PO twice daily if original dose was 25 mg/m2 twice daily and 15 mg/m2 PO twice daily if original dose was 20 mg/m2 twice daily. If mifepristone is discontinued, resume the original selumetinib dose after 3 elimination half-lives of mifepristone. Selumetinib is a CYP3A4 substrate and mifepristone is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased selumetinib exposure by 49%.
    Sertraline: (Major) Avoid use of mifepristone with other QT interval prolonging drugs, such as sertraline. Mifepristone is associated with dose-related prolongation of the QT interval. QTc prolongation and torsade de pointes (TdP) have been reported during postmarketing use of sertraline; most cases had confounding risk factors. The risk of sertraline-induced QT prolongation is generally considered to be low in clinical practice. Its effect on QTc interval is minimal (typically less than 5 msec), and the drug has been used safely in patients with cardiac disease (e.g., recent myocardial infarction, unstable angina, chronic heart failure).
    Sevoflurane: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with mifepristone. Halogenated anesthetics can prolong the QT interval. Mifepristone has been associated with dose-dependent prolongation of the QT interval. There is no experience with high exposure or concomitant use with other QT prolonging drugs. To minimize the risk of QT prolongation, the lowest effective dose should always be used.
    Short-acting beta-agonists: (Minor) Mifepristone has been associated with dose-dependent prolongation of the QT interval. There is no experience with high exposure or concomitant use with other QT prolonging drugs. To minimize the risk of QT prolongation, the lowest effective dose of mifepristone should always be used. Drugs with a possible risk for QT prolongation that should be used cautiously with mifepristone include the beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Sibutramine: (Moderate) Consider alternatives to sibutramine if possible due to the risk for serotonin-related adverse reactions resulting from a probable increase in sibutramine exposure. If used together, use the lowest dose of sibutramine and monitor closely. If serotonin syndrome occurs, discontinue sibutramine and any other serotonergic drugs. Mifepristone is a CYP3A4 inhibitor and is expected to increase exposure of CYP3A4 substrates, such as sibutramine.
    Sildenafil: (Major) Avoid use of sildenafil in patients taking mifepristone chronically for hormonal conditions, such as Cushing's syndrome, due to the potential for increase sildenafil exposure. Consider alternatives to sildenafil if possible. If medically necessary, it is advisable to initiate sildenafil at the lowest dose for the condition being treated, with careful adjustment to efficacy as clinically indicated and tolerated. Monitor for sildenafil-related side effects, such as hypotension, syncope, chest pain, hearing or vision changes, or priapism. Mifepristone is a CYP3A4 and 2C9 inhibitor. Sildenafil metabolism is principally mediated by the CYP3A (major route) and CYP2C9 (minor route). Inhibitors of these enzymes are expected to reduce sildenafil clearance. Due to the slow elimination of mifepristone from the body, any interactions that occur may be prolonged.
    Silodosin: (Moderate) Silodosin is extensively metabolized by hepatic cytochrome P450 3A4 and is a P-glycoprotein (P-gp) substrate. In theory, drugs that inhibit CYP3A4 and P-gp such as mifepristone may cause significant increases in silodosin plasma concentrations.
    Simeprevir: (Moderate) Use caution when using mifepristone chronically with simeprevir. Mifepristone may increase the plasma concentrations of simeprevir, resulting in adverse effects, such as rash, abdominal pain, diarrhea, or headache. Mifepristone is an inhibitor of CYP3A4 and may also inhibit P-glycoprotein (P-gp). When mifepristone is used chronically for hormonal conditions, such as Cushing's syndrome, drug interactions are likely with CYP3A substrates. Simeprevir is primarily metabolized by CYP3A4. Due to the slow elimination of mifepristone from the body, any interaction that occurs may be observed for a prolonged period after mifepristone administration.
    Simvastatin: (Contraindicated) When mifepristone is used in the treatment of Cushing's syndrome, coadministration is contraindicated based on studies demonstrating significant simvastatin exposure increases which may lead to an increased risk of myopathy and rhabdomyolysis. Consider interruption of simvastatin therapy during use of mifepristone for pregnancy termination. Due to the slow elimination of mifepristone from the body, such interactions may be observed for a prolonged period after mifepristone administration. Mifepristone is a strong CYP3A4 inhibitor; simvastatin is a sensitive CYP3A4 substrate. Coadministration of mifepristone and simvastatin increased simvastatin and simvastatin acid exposure by 10.4-fold and 15.7-fold, respectively, in drug interaction studies.
    Simvastatin; Sitagliptin: (Contraindicated) When mifepristone is used in the treatment of Cushing's syndrome, coadministration is contraindicated based on studies demonstrating significant simvastatin exposure increases which may lead to an increased risk of myopathy and rhabdomyolysis. Consider interruption of simvastatin therapy during use of mifepristone for pregnancy termination. Due to the slow elimination of mifepristone from the body, such interactions may be observed for a prolonged period after mifepristone administration. Mifepristone is a strong CYP3A4 inhibitor; simvastatin is a sensitive CYP3A4 substrate. Coadministration of mifepristone and simvastatin increased simvastatin and simvastatin acid exposure by 10.4-fold and 15.7-fold, respectively, in drug interaction studies.
    Siponimod: (Major) Concomitant use of siponimod and mifepristone is not recommended due to a significant increase in siponimod exposure. Additionally, both drugs are associated with QT prolongation. Siponimod is a CYP2C9 and CYP3A4 substrate; mifepristone is a moderate CYP2C9/strong CYP3A4 dual inhibitor. Coadministration with a moderate CYP2C9/CYP3A4 dual inhibitor led to a 2-fold increase in the exposure of siponimod.
    Sirolimus: (Contraindicated) Coadministration of sirolimus is contraindicated when mifepristone is used chronically, such as in the treatment of Cushing's syndrome. Mifepristone, a CYP3A4 inhibitor, is likely to increase sirolimus concentrations and adverse effects, since sirolimus is a CYP3A4 substrate with a narrow therapeutic index. Due to the slow elimination of mifepristone from the body, such interactions may be observed for a prolonged period after mifepristone administration.
    Sofosbuvir; Velpatasvir: (Moderate) Use caution when administering velpatasvir with mifepristone. Taking these drugs together may increase the plasma concentrations of velpatasvir, potentially resulting in adverse events. Velpatasvir is a substrate of the drug transporter P-glycoprotein (P-gp); mifepristone is an inhibitor of P-gp. Mifepristone is also an inhibitor of the hepatic enzyme CYP3A4. Velpatasvir is a CYP3A4 substrate.
    Sofosbuvir; Velpatasvir; Voxilaprevir: (Moderate) Use caution when administering velpatasvir with mifepristone. Taking these drugs together may increase the plasma concentrations of velpatasvir, potentially resulting in adverse events. Velpatasvir is a substrate of the drug transporter P-glycoprotein (P-gp); mifepristone is an inhibitor of P-gp. Mifepristone is also an inhibitor of the hepatic enzyme CYP3A4. Velpatasvir is a CYP3A4 substrate.
    Solifenacin: (Moderate) Due to a possible risk for QT prolongation and torsade de pointes (TdP), mifepristone and solifenacin should be used together cautiously. Mifepristone has been associated with dose-dependent prolongation of the QT interval. There is no experience with high exposure or concomitant use with other QT prolonging drugs. To minimize the risk of QT prolongation, the lowest effective dose should always be used. Drugs with a possible risk for QT prolongation and torsades de pointes that should be used cautiously with mifepristone include solifenacin.
    Sonidegib: (Major) Avoid concomitant use of sonidegib and chronic use of mifepristone as increased sonidegib plasma are expected, resulting in an increased risk of adverse events, particularly musculoskeletal toxicity. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown. Mifepristone is a strong CYP3A4 inhibitor and may significantly increase the level of the CYP3A4 substrate, sonidegib. Coadministration of another strong CYP3A4 inhibitor increased the mean Cmax and AUC of sonidegib by 2.2-fold and 1.5-fold, respectively.
    Sorafenib: (Major) Avoid coadministration of sorafenib with mifepristone due to the risk of additive QT prolongation. Sorafenib is associated with QTc prolongation. Mifepristone is associated with dose-related prolongation of the QT interval.
    Sotalol: (Major) Mifepristone should be used cautiously and with close monitoring with sotalol. Sotalol administration is associated with QT prolongation and torsades de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. Mifepristone has been associated with dose-dependent prolongation of the QT interval. There is no experience with high exposure or concomitant use with other QT prolonging drugs. To minimize the risk of QT prolongation, the lowest effective dose should always be used.
    St. John's Wort, Hypericum perforatum: (Major) Avoid the use of mifepristone and potent CYP3A inducers such as St. John's wort. St. John's wort may induce mifepristone metabolism via CYP3A4. It is not known if lowered mifepristone serum levels would lead to reduced response or therapeutic failure. If use together is medically necessary, monitor the patient closely to ensure the proper therapeutic response is obtained.
    Sufentanil: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if mifepristone must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of mifepristone is necessary. If mifepristone is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate, and coadministration with a strong CYP3A4 inhibitor like mifepristone can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If mifepristone is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
    Sulindac: (Moderate) Mifepristone significantly increased exposure of drugs metabolized by CYP2C8/2C9 in interaction studies. Therefore, when mifepristone is used chronically, as in the treatment of Cushing's syndrome, use caution with coadministered CYP2C8/2C9 substrates, including the NSAIDs. Use the lowest doses of the substrate and patients should be monitored closely for adverse reactions.
    Sunitinib: (Major) Avoid use of mifepristone with sunitinib due to the risk of QT prolongation; increased sunitinib exposure may also occur. Sunitinib is a CYP3A4 substrate that can prolong the QT interval. Mifepristone is a strong CYP3A4 inhibitor that is associated with dose-related prolongation of the QT interval. Coadministration with another strong CYP3A4 inhibitor increased exposure to sunitinib and its primary active metabolite by 51%. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
    Suvorexant: (Major) Coadministration of suvorexant and chronic mifepristone therapy is not recommended due to the potential for significantly increased suvorexant exposure. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown. Suvorexant is a CYP3A4 substrate. Mifepristone is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the suvorexant AUC by 2.8-fold.
    Tacrolimus: (Contraindicated) Coadministration of systemic tacrolimus is contraindicated when mifepristone is used chronically, such as in the treatment of Cushing's syndrome. Mifepristone, a CYP3A4 inhibitor, is likely to increase tacrolimus concentrations and adverse effects, since tacrolimus is a CYP3A4 substrate with a narrow therapeutic index. Due to the slow elimination of mifepristone from the body, such interactions may be observed for a prolonged period after mifepristone administration.
    Tadalafil: (Moderate) It is advisable to initiate tadalafil at the lowest dose for the condition being treated, with careful adjustment to efficacy as clinically indicated and tolerated. Monitor for tadalafil-related side effects, such as hypotension, syncope, chest pain, hearing or vision changes, or priapism. Mifepristone inhibits CYP3A4 and is expected to increase exposure of CYP3A4 substrates, such as tadalafil. Moderate CYP3A inhibitors would likely increase tadalafil exposure. Due to the slow elimination of mifepristone from the body, such interactions may be observed for a prolonged period after mifepristone administration.
    Talazoparib: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with mifepristone is necessary. Talazoparib is a P-glycoprotein (P-gp) substrate and mifepristone is a P-gp inhibitor. Coadministration with other P-gp inhibitors increased talazoparib exposure by 8% to 45%.
    Tamoxifen: (Moderate) Use caution if coadministration of mifepristone with tamoxifen is necessary due to the risk of QT prolongation; always use the lowest effective dose of mifepristone. Mifepristone has been associated with dose-dependent prolongation of the QT interval. Tamoxifen has also been reported to prolong the QT interval, usually in overdose or when used in high doses. Rare case reports of QT prolongation have also been described when tamoxifen is used at lower doses.
    Tamsulosin: (Moderate) Use caution when administering tamsulosin with a moderate CYP3A4 inhibitor such as mifepristone. If concomitant use in necessary, monitor patient closely for increased side effects, including hypotension, since tamsulosin exposure may be increased. Tamsulosin is extensively metabolized by CYP3A4. In clinical evaluation, concomitant treatment with a strong CYP3A4 inhibitor resulted in significant increases in tamsulosin exposure; interactions with moderate CYP3A4 inhibitors have not been evaluated. However, mifepristone is expected to increase concentrations of CYP3A4 substrates. Due to the slow elimination of mifepristone from the body, any interactions that do occur may be prolonged.
    Tazemetostat: (Major) Avoid coadministration of tazemetostat with mifepristone as concurrent use may increase tazemetostat exposure and the frequency and severity of adverse reactions. Tazemetostat is a CYP3A4 substrate and mifepristone is a strong CYP3A4 inhibitor. Coadministration of a moderate CYP3A4 inhibitor increased tazemetostat exposure by 3.1-fold.
    Telaprevir: (Moderate) Close clinical monitoring is advised when administering mifepristone with telaprevir due to an increased potential for mifepristone-related adverse events. If mifepristone dose adjustments are made, re-adjust the dose upon completion of telaprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathways of mifepristone and telaprevir. Both mifepristone and telaprevir are substrates and inhibitors of the hepatic isoenzyme CYP3A4. Additionally, mifepristone is an inhibitor of the drug efflux transporter P-glycoprotein (PGP); telaprevir is partially metabolized by this efflux protein. When used in combination, the plasma concentrations of both medications may be elevated. In general, caution is warranted when mifepristone is used in the treatment of Cushing's syndrome and coadministered with drugs that inhibit CYP3A4; limit the dose of mifepristone to 300 mg/day PO during times of coadministration.
    Telavancin: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), mifepristone and telavancin should be used together cautiously. Mifepristone has been associated with dose-dependent prolongation of the QT interval. There is no experience with high exposure or concomitant use with other QT prolonging drugs. To minimize the risk of QT prolongation, the lowest effective dose should always be used. Telavancin has been associated with QT prolongation.
    Telithromycin: (Major) Avoid coadministration of mifepristone with telithromycin due to the risk of additive QT prolongation and torsade de pointes (TdP); the exposure of both drugs may also be increased. If concomitant use of mifepristone is necessary for the treatment of Cushing's syndrome in a patient already receiving telithromycin, initiate mifepristone at a dose of 300 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with telithromycin is initiated in a patient already receiving mifepristone 300 mg, dosage adjustments are not required. If therapy with telithromycin is initiated in a patient already receiving mifepristone 600 mg, reduce dose of mifepristone to 300 mg and titrate to a maximum of 600 mg if clinically indicated. If therapy with telithromycin is initiated in a patient already receiving 900 mg, reduce dose of mifepristone to 600 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with telithromycin is initiated in a patient already receiving 1,200 mg, reduce the mifepristone dose to 900 mg. Both mifepristone and telithromycin are substrates and strong inhibitors of CYP3A4 that are associated with QT prolongation.
    Temsirolimus: (Major) Avoid chronic coadministration of mifepristone with temsirolimus due to increased plasma concentrations of the primary active metabolite of temsirolimus (sirolimus). If concomitant use is unavoidable, consider reducing the dose of temsirolimus to 12.5 mg per week. Allow a washout period of approximately 1 week after discontinuation of mifepristone before increasing temsirolimus to its original dose. Temsirolimus is a CYP3A4 substrate and mifepristone is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor did not significantly affect temsirolimus exposure, but increased the AUC and Cmax of sirolimus by 3.1-fold and 2.2-fold, respectively. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
    Tenofovir Alafenamide: (Moderate) Coadministration of mifepristone and tenofovir alafenamide may result in elevated tenofovir concentrations. Mifepristone is an inhibitor of the drug transporter P-glycoprotein (P-gp). Tenofovir alafenamide is a substrate for P-gp. Of note, when tenofovir alafenamide is administered as part of a cobicistat-containing product, its availability is increased by cobicistat and a further increase of tenofovir alafenamide concentrations is not expected upon coadministration of an additional P-gp inhibitor.
    Tenofovir, PMPA: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as mifepristone. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
    Tepotinib: (Major) Avoid concomitant use of tepotinib and mifepristone due to increased plasma concentrations of tepotinib, which may increase the incidence and severity of adverse reactions. Tepotinib is a CYP3A and P-gp substrate; mifepristone is a dual strong CYP3A and P-gp inhibitor.
    Tetrabenazine: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), concurrent use of mifepristone and tetrabenazine should be avoided if possible. Mifepristone has been associated with dose-dependent prolongation of the QT interval. There is no experience with high exposure or concomitant use with other QT prolonging drugs. To minimize the risk of QT prolongation, the lowest effective dose should always be used. Tetrabenazine causes a small increase in the corrected QT interval (QTc).
    Tezacaftor; Ivacaftor: (Major) If mifepristone and ivacaftor are taken together, administer ivacaftor at the usual recommended dose but reduce the frequency to twice weekly. Ivacaftor is a CYP3A substrate, and mifepristone is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased ivacaftor exposure by 8.5-fold. (Major) Reduce the dosing frequency of tezacaftor; ivacaftor when coadministered with mifepristone; coadministration may increase tezacaftor; ivacaftor exposure and adverse reactions. When combined, dose 1 tezacaftor; ivacaftor combination tablet twice a week, approximately 3 to 4 days apart (i.e., Day 1 and Day 4). The evening dose of ivacaftor should not be taken. Both tezacaftor and ivacaftor are CYP3A substrates (ivacaftor is a sensitive substrate); mifepristone is a strong CYP3A inhibitor. Coadministration of a strong CYP3A inhibitor increased tezacaftor and ivacaftor exposure 4- and 15.6-fold, respectively.
    Thioridazine: (Contraindicated) Thioridazine is associated with a well-established risk of QT prolongation and torsades de pointes (TdP).Thioridazine is considered contraindicated for use along with agents that, when combined with a phenothiazine, may prolong the QT interval and increase the risk of TdP, or cause orthostatic hypotension. Because of the potential for TdP, use of mifepristone with thioridazine is contraindicated.
    Thiotepa: (Major) Avoid the concomitant use of thiotepa and chronic use of mifepristone if possible; reduced metabolism to the active thiotepa metabolite may result in decreased thiotepa efficacy. Consider an alternative agent with no or minimal potential to inhibit CYP3A4. If coadministration is necessary, monitor patients for signs of reduced thiotepa efficacy.The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown. In vitro, thiotepa is metabolized via CYP3A4 to the active metabolite, TEPA; mifepristone is a strong CYP3A4 inhibitor.
    Thrombin Inhibitors: (Major) When mifepristone is used for the termination of pregnancy, concurrent use of anticoagulants is contraindicated due to the increased risk of serious bleeding. Consider an alternative to mifepristone in these circumstances. When mifepristone is used for other condtions, such as Cushing's disease, an interaction with thrombin inhibitors is not expected; however, follow usual cautions and monitor as per standard of care.
    Ticagrelor: (Moderate) Use together with caution and monitor for evidence of increased antiplatelet effect, as well as side effects such as bleeding and dyspnea. CYP3A inhibitors may increase ticagrelor exposure and so increase the risk of dyspnea, bleeding, and other adverse events. No dose adjustment has been recommended. Ticagrelor is a CYP3A4 and P-glycoprotein (P-gp) substrate. Mifepristone inhibits CYP3A4 and may be a P-gp inhibitor. Due to the slow elimination of mifepristone from the body, any interactions that occur may be prolonged.
    Tinzaparin: (Major) When mifepristone is used for the termination of pregnancy, concurrent use of anticoagulants is contraindicated due to the increased risk of serious bleeding. Consider an alternative to mifepristone in these circumstances. When mifepristone is used chronically for other conditions, such as Cushing's disease, an interaction with low-molecular weight heparins is not expected; however, follow usual cautions and monitor as per standard of care.
    Tipranavir: (Major) Caution is advised when administering tipranavir with mifepristone because increased serum concentrations of either drug may occur. When mifepristone is used in the treatment of Cushing's syndrome, coadministration with tipranavir should be done only when necessary, and in such cases the dose of mifepristone should be limited to a maximum dose of 900 mg per day. In a patient already receiving tipranavir, initiate mifepristone at a dose of 300 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with tipranavir is initiated in a patient already receiving mifepristone 300 mg, dosage adjustments are not required. If therapy with tipranavir is initiated in a patient already receiving mifepristone 600 mg, reduce dose of mifepristone to 300 mg and titrate to a maximum of 600 mg if clinically indicated. If therapy with tipranavir is initiated in a patient already receiving 900 mg, reduce dose of mifepristone to 600 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with tipranavir is initiated in a patient already receiving 1,200 mg, reduce the mifepristone dose to 900 mg. Both mifepristone and tipranavir are substrates and strong inhibitors of CYP3A4.
    Tofacitinib: (Major) A dosage reduction of tofacitinib is necessary if coadministered with chronic mifepristone therapy. In patients receiving 5 mg or less twice daily, reduce to once daily dosing; in patients receiving 10 mg twice daily, reduce to 5 mg twice daily; in patients receiving 22 mg once daily of the extended-release (XR) formulation, switch to 11 mg XR once daily; in patients receiving 11 mg XR once daily, switch to the immediate-release formulation at a dose of 5 mg once daily.. Tofacitinib exposure is increased when coadministered with mifepristone. Mifepristone is a strong CYP3A4 inhibitor; tofacitinib is a CYP3A4 substrate. When mifepristone is given chronically, the half-life of the drug is prolonged, and drug-interaction potential is extended. Coadministration with another strong CYP3A4 inhibitor increased tofacitinib exposure by 2-fold. The clinical significance of this interaction when mifepristone is used in a regimen for pregnancy termination is unknown.
    Tolmetin: (Moderate) Mifepristone significantly increased exposure of drugs metabolized by CYP2C8/2C9 in interaction studies. Therefore, when mifepristone is used chronically, as in the treatment of Cushing's syndrome, use caution with coadministered CYP2C8/2C9 substrates, including the NSAIDs. Use the lowest doses of the substrate and patients should be monitored closely for adverse reactions.
    Tolterodine: (Major) Reduce the dose of immediate-release tolterodine to 1 mg twice daily and extended-release tolterodine to 2 mg once daily and monitor for evidence of QT prolongation if coadministered with chronic mifepristone therapy. Concurrent use may increase tolterodine exposure. Mifepristone has been associated with dose-dependent prolongation of the QT interval and when administered chronically is a strong CYP3A4 inhibitor. Tolterodine has been associated with dose-dependent prolongation of the QT interval, especially in poor CYP2D6 metabolizers. In CYP2D6 poor metabolizers, the CYP3A4 pathway becomes important in tolterodine elimination. Because it is difficult to assess which patients will be poor CYP2D6 metabolizers, reduced doses of tolterodine are advised when administered with strong CYP3A4 inhibitors. In a drug interaction study, coadministration of a strong CYP3A4 inhibitor increased the tolterodine AUC by 2.5-fold in CYP2D6 poor metabolizers. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
    Tolvaptan: (Contraindicated) The concomitant use of tolvaptan and chronic mifepristone therapy is contraindicated. Concurrent use is expected to increase tolvaptan exposure. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown. Tolvaptan is a sensitive CYP3A4 substrate; mifepristone is a strong inhibitor of CYP3A4. Coadministration of another strong CYP3A4 inhibitor increased tolvaptan exposure 5-fold. No data exists regarding the appropriate dose adjustment needed to allow safe administration of tolvaptan with strong CYP3A4 inhibitors.
    Topotecan: (Major) Avoid coadministration of mifepristone with oral topotecan due to increased topotecan exposure; mifepristone may be administered with intravenous topotecan. Oral topotecan is a substrate of P-glycoprotein (P-gp) and mifepristone is a P-gp inhibitor. Oral administration within 4 hours of another P-gp inhibitor increased the dose-normalized AUC of topotecan lactone and total topotecan 2-fold to 3-fold compared to oral topotecan alone.
    Toremifene: (Major) Avoid coadministration of mifepristone with toremifene if possible due to increased plasma concentrations of toremifene which may result in QT prolongation. If concomitant use is unavoidable, closely monitor ECGs for QT prolongation and monitor electrolytes; correct hypokalemia or hypomagnesemia prior to administration of toremifene. To minimize the risk of QT prolongation, the lowest effective dose of mifepristone should always be used. Toremifene is a CYP3A4 substrate that has been shown to prolong the QTc interval in a dose- and concentration-related manner. Mifepristone is a strong CYP3A4 inhibitor that has also been associated with dose-dependent prolongation of the QT interval. Coadministration with another strong CYP3A4 inhibitor increased toremifene exposure by 2.9-fold; exposure to N-demethyltoremifene was reduced by 20%. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
    Trabectedin: (Major) Avoid the concomitant use of trabectedin with chronic use of mifepristone due to the risk of increased trabectedin exposure. If short-term mifepristone (less than 14 days) cannot be avoided, begin administration 1 week after the trabectedin infusion and discontinue it the day prior to the next trabectedin infusion. Trabectedin is a CYP3A substrate and mifepristone is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the systemic exposure of a single dose of trabectedin (0.58 mg/m2 IV) by 66% compared to a single dose of trabectedin (1.3 mg/m2) given alone.
    Trandolapril; Verapamil: (Moderate) Monitor blood pressure and heart rate if coadministration of verapamil with mifepristone is necessary. Concurrent use may result in elevated verapamil concentrations. Verapamil is a CYP3A4 substrate and mifepristone is a strong CYP3A4 inhibitor.
    Trazodone: (Major) Avoid coadministration of trazodone and mifepristone due to the potential for additive effects on the QT interval; increased exposure to trazodone may also occur. Both trazodone and mifepristone are associated with QT prolongation; there are also postmarketing reports of torsade de pointes with trazodone. In addition, concurrent use may lead to substantial increases in trazodone plasma concentrations, further increasing the risk for adverse effects. If trazodone must be used with a potent CYP3A4 inhibitor, such as mifepristone, a lower dose of trazodone should be considered.
    Triazolam: (Contraindicated) Coadministration of triazolam, a primary CYP3A4 substrate, with strong CYP3A4 inhibitors, such as mifepristone, is contraindicated by the manufacturer of triazolam due to the risk for increased and prolonged sedation and respiratory depression. Concurrent use is expected to produce large increases in systemic exposure to triazolam, with the potential for serious adverse effects. Mifepristone inhibits CYP3A4 when it is used chronically in the treatment of hormonal conditions, such as Cushing's disease. Due to the slow elimination of mifepristone from the body, such interactions may be observed for a prolonged period after mifepristone administration.
    Triclabendazole: (Moderate) Monitor ECG and use the lowest effective dose of mifepristone if triclabendazole is coadministered due to the potential for additive QT prolongation. Mifepristone has been associated with dose-dependent prolongation of the QT interval. Transient prolongation of the mean QTc interval was noted on the ECG recordings in dogs administered triclabendazole.
    Tricyclic antidepressants: (Minor) Due to a possible risk for QT prolongation and torsade de pointes (TdP), mifepristone and tricyclic antidepressants should be used together cautiously. Mifepristone has been associated with dose-dependent prolongation of the QT interval. There is no experience with high exposure or concomitant use with other QT prolonging drugs. To minimize the risk of QT prolongation, the lowest effective dose should always be used. Drugs with a possible risk for QT prolongation and torsades de pointes that should be used cautiously with mifepristone include tricyclic antidepressants.
    Trifluoperazine: (Minor) Due to a possible risk for QT prolongation and torsade de pointes (TdP), mifepristone and trifluoperazine should be used together cautiously. Mifepristone has been associated with dose-dependent prolongation of the QT interval. There is no experience with high exposure or concomitant use with other QT prolonging drugs. To minimize the risk of QT prolongation, the lowest effective dose should always be used. Drugs with a possible risk for QT prolongation and torsades de pointes that should be used cautiously with mifepristone include trifluoperazine.
    Trimipramine: (Minor) Due to a possible risk for QT prolongation and torsade de pointes (TdP), mifepristone and tricyclic antidepressants should be used together cautiously. Mifepristone has been associated with dose-dependent prolongation of the QT interval. There is no experience with high exposure or concomitant use with other QT prolonging drugs. To minimize the risk of QT prolongation, the lowest effective dose should always be used. Drugs with a possible risk for QT prolongation and torsades de pointes that should be used cautiously with mifepristone include tricyclic antidepressants.
    Triptorelin: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., triptorelin) outweigh the potential risks of QT prolongation in patients receiving mifepristone. To minimize the risk of QT prolongation, the lowest effective dose of mifepristone should always be used. Mifepristone has been associated with dose-dependent prolongation of the QT interval. Androgen deprivation therapy may prolong the QT/QTc interval.
    Tucatinib: (Major) Caution is advised when administering tucatinib with mifepristone because increased serum concentrations of either drug may occur. When mifepristone is used in the treatment of Cushing's syndrome, coadministration with tucatinib should be done only when necessary, and in such cases the dose of mifepristone should be limited to a maximum dose of 900 mg per day. In a patient already receiving tucatinib, initiate mifepristone at a dose of 300 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with tucatinib is initiated in a patient already receiving mifepristone 300 mg, dosage adjustments are not required. If therapy with tucatinib is initiated in a patient already receiving mifepristone 600 mg, reduce dose of mifepristone to 300 mg and titrate to a maximum of 600 mg if clinically indicated. If therapy with tucatinib is initiated in a patient already receiving 900 mg, reduce dose of mifepristone to 600 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with tucatinib is initiated in a patient already receiving 1,200 mg, reduce the mifepristone dose to 900 mg. Mifepristone is a CYP3A4 substrate, a strong CYP3A4 inhibitor, and a moderate CYP2C8 inhibitor; tucatinib is a CYP2C8 substrate and strong CYP3A4 inhibitor.
    Ubrogepant: (Contraindicated) Coadministration of ubrogepant and mifepristone is contraindicated as concurrent use may increase ubrogepant exposure and the risk of adverse effects. Ubrogepant is a CYP3A4 substrate; mifepristone is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor resulted in a 9.7-fold increase in the exposure of ubrogepant.
    Upadacitinib: (Moderate) Use upadacitinib with caution in patients receiving chronic treatment with mifepristone as upadacitinib exposure and adverse effects may be increased. Upadacitinib is a CYP3A4 substrate; mifepristone is a strong CYP3A4 inhibitor. Concurrent use of upadacitinib with a strong inhibitor increased upadacitinib exposure by 75%. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
    Valdecoxib: (Moderate) Mifepristone significantly increased exposure of drugs metabolized by CYP2C8/2C9 in interaction studies. Therefore, when mifepristone is used chronically, as in the treatment of Cushing's syndrome, use caution with coadministered CYP2C8/2C9 substrates, including the NSAIDs. Use the lowest doses of the substrate and patients should be monitored closely for adverse reactions.
    Vandetanib: (Major) Avoid coadministration of vandetanib with mifepristone due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, use the lowest effective dose of mifepristone, monitor ECGs for QT prolongation, and monitor electrolytes. Correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Both drugs can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib.
    Vardenafil: (Major) Do not use vardenafil orally disintegrating tablets with mifepristone due to increased vardenafil exposure; do not exceed a single dose of 2.5 mg per 24-hour period of vardenafil oral tablets. Vardenafil is primarily metabolized by CYP3A4/5; mifepristone is a strong CYP3A4 inhibitor. Coadministration with other strong CYP3A4 inhibitors increased the AUC of vardenafil by 10- to 16-fold. There may also be an increased risk of QT prolongation and torsade de pointes (TdP) during coadministration of vardenfil and mifepristone. Vardenafil is associated with QT prolongation. Both therapeutic and supratherapeutic doses of vardenafil can produce an increase in QTc interval. Mifepristone has been associated with dose-dependent prolongation of the QT interval.
    Vemurafenib: (Major) Avoid vemurafenib in patients receiving medications known to prolong the QT interval such as mifepristone. Vemurafenib has been shown to prolong the QT interval in a concentration-dependent manner. The ECG changes occurred within the first month of treatment. Mifepristone has also been associated with dose-dependent prolongation of the QT interval. Additionally, coadministration may result in increased vemurafenib exposure and an increased risk of adverse events, including QT prolongation. Vemurafenib is a CYP3A4 substrate; mifepristone is a strong CYP3A4 inhibitor. Because of the prolonged action of mifepristone, the effects on CYP3A may be prolonged. Coadministration with another strong CYP3A4 inhibitor increased the exposure of vemurafenib by 40%.
    Venetoclax: (Major) Coadministration of mifepristone with venetoclax is contraindicated during the initiation and ramp-up phase in patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL); consider an alternative medication or adjust the venetoclax dose with close monitoring for toxicity (e.g., hematologic toxicity, GI toxicity, and tumor lysis syndrome) in patients receiving a steady daily dose of venetoclax if concurrent use is necessary. In patients with acute myeloid leukemia (AML), reduce the venetoclax dose and monitor for toxicity during concurrent use. Resume the original venetoclax dose 2 to 3 days after discontinuation of mifepristone. Specific venetoclax