PDR MEMBER LOGIN:
  • PDR Search

    Required field
  • Advertisement
  • CLASSES

    Cytostatic Gonadotropin-releasing Hormone Analogs
    Gonadotropin-releasing Hormones

    DEA CLASS

    Rx

    DESCRIPTION

    Synthetic analog of gonadotropin-releasing hormone (GnRH); substitution of two amino acids normally found in GnRH leads to sustained activity
    Approved uses include endometriosis, precocious puberty, prostate cancer, and uterine leiomyomata; off-label uses include benign prostatic hyperplasia (BPH), breast cancer, infertility, premenstrual syndrome (PMS), and stuttering priapism
    Pregnancy category X

    COMMON BRAND NAMES

    Eligard, Lupron, Lupron Depot, Lupron Depot-Ped

    HOW SUPPLIED

    Eligard Subcutaneous Inj Susp: 7.5mg, 22.5mg, 30mg, 45mg
    Leuprolide Acetate/Lupron Subcutaneous Inj Sol: 0.2mL, 1mg
    Lupron Depot/Lupron Depot-Ped Intramuscular Inj Pwd F/Susp: 3.75mg, 7.5mg, 11.25mg, 15mg, 22.5mg, 30mg, 45mg

    DOSAGE & INDICATIONS

    For the palliative treatment of advanced prostate cancer, particularly when orchiectomy or estrogen therapy are not indicated or are unacceptable.
    Subcutaneous dosage (solution for injection)
    Adults

    1 mg subcutaneous once daily.

    Subcutaneous dosage (Eligard)
    Adults

    Several dosage regimens are possible, depending on the depot dosage used. 7.5 mg subcutaneous (depot injection) once monthly, 22.5 mg subcutaneous (depot injection) every 3 months, 30 mg subcutaneous (depot injection) every 4 months, or 45 mg subcutaneous (depot injection) every 6 months.

    Intramuscular (injection depot suspension)
    Adults

    7.5 mg intramuscularly once monthly; treatment is usually continued upon development of metastatic castration-resistant prostate cancer. Due to different release characteristics, a fractional dose of the 3-month, 4-month, or 6-month depot formulation is not equivalent to the same dose of the monthly formulation and should not be given. After a brief increase in testosterone levels, serum testosterone was suppressed to castrate range within 30 days of the initial injection of leuprolide depot in 94% of patients with previously untreated stage D2 prostate cancer (n = 56), and in all patients by 66 days. At week 12, 77% of patients had not progressed (complete or partial response, or stable disease); 84% of patients had no progression at week 24. Local disease improved or remained stable in all patients at week 12, and in 98% of patients at week 24.

    Intramuscular dosage
    Adults

    22.5 mg intramuscularly every 3 months (12 weeks); treatment is usually continued upon development of metastatic castration-resistant prostate cancer. Due to different release characteristics, a fractional dose of the 3-month, 4-month, or 6-month depot formulation is not equivalent to the same dose of the monthly formulation and should not be given. In clinical studies, serum testosterone was suppressed to castrate levels within 30 days in 95% of patients; two additional patients had castrate levels within 45 days, and castrate levels were reached in another 2 patients by 15 and 28 weeks, respectively. During the initial 24 weeks of treatment, 85% of patient did not progress. At least a 90% decrease from baseline in serum PSA was reported in 71% of patients, while 63% of patients had PSA levels decrease to within the normal range.

    Intramuscular dosage
    Adults

    30 mg intramuscularly every 4 months (16 weeks); treatment is usually continued upon development of metastatic castration-resistant prostate cancer. Due to different release characteristics, a fractional dose of the 3-month, 4-month, or 6-month depot formulation is not equivalent to the same dose of the monthly formulation and should not be given. After a brief increase in testosterone levels during the first week of treatment with leuprolide depot, mean serum testosterone fell below castrate levels within 30 days of the first injection in 94% of patients with previously untreated stage D2 prostatic adenocarcinoma in a multicenter, open-label, single-arm clinical trial (n = 49); all patients reached castrate levels within 43 days. At week 16, 86% of patient had not progressed (complete or partial response, or stable disease); at week 32, 77% of patients had not progressed. Local disease improved or remained stable in all patients at weeks 16 and 32. Fifty percent of patients with elevated baseline PSA had a normal PSA at week 16, and 51% had normal PSA at week 32.

    Intramuscular dosage
    Adults

    45 mg intramuscularly every 6 months (24 weeks); treatment is usually continued upon development of metastatic castration-resistant prostate cancer. Due to different release characteristics, a fractional dose of the 3-month, 4-month, or 6-month depot formulation is not equivalent to the same dose of the monthly formulation and should not be given. After a brief increase in serum testosterone levels, testosterone was suppressed to castrate levels from week 4 to week 48 in 93.4% of patients with prostate cancer treated with leuprolide depot 45 mg IM every 6 months in a multicenter, open-label, single-arm clinical trial (n = 148).

    For the management of endometriosis including pain relief and reduction of endometriotic lesions.
    Intramuscular dosage (injection suspension)
    Adult females

    Initially, 3.75 mg IM once monthly OR 11.25 mg IM once every 3 months, given with or without norethindrone acetate 5 mg/day PO for a therapy duration of 6 months. For recurrence of symptoms, may use either leuprolide dose with norethindrone acetate 5 mg/day PO for 6 months. Use of greater than 1 re-treatment period is NOT recommended. Assessment of bone density is recommended before retreatment; leuprolide monotherapy is NOT recommended for re-treatment. Clinical guidelines/studies suggest the addition of hormonal add-back therapy (e.g., estrogens and/or progestins) is effective at reducing the bone mineral loss which occurs with leuprolide therapy alone. Such therapy does not compromise the efficacy of leuprolide in relieving endometriosis symptoms and may also reduce vasomotor symptoms and vaginal dryness associated with hypoestrogenism.

    For the treatment of central precocious puberty (idiopathic or neurogenic) in children.
    NOTE: Leuprolide has been designated an orphan drug by the FDA for this indication.
    NOTE: Downregulation is determined by GnRH agonist stimulation test, sex steroid concentrations, and Tanner staging. Give consideration to discontinuing treatment before 11 years of age in girls and 12 years of age in boys.
    Once monthly regimen.
    Intramuscular dosage (injection suspension, Lupron Depot-Ped 1-month)

    NOTE: Do not use partial syringes or a combination of syringes to achieve a particular dose or to titrate dosages. Each 1-month depot syringe dose strength and formulation has different release characteristics.

    Children > 37.5 kg

    The recommended dose is 15 mg IM as a single dose repeated every 4 weeks. In clinical trials, patients receiving this dosage ranged from 39.3 to 57.5 kg body weight. May adjust dose if changes in body weight occur. Monitor hormonal and clinical parameters at month 1 to 2, with dose changes, and further as appropriate to ensure adequate suppression.

    Children 25 to 37.5 kg

    The recommended dose is 11.25 mg IM as a single dose repeated every 4 weeks. Increase dose if needed to the next available higher dose (e.g., 15 mg) at next monthly injection until total down-regulation is achieved. May adjust dose if changes in body weight occur. In clinical trials, patients receiving the 11.25 mg dosage ranged from 28.4 to 36.8 kg body weight. Monitor hormonal and clinical parameters at month 1 to 2, with dose changes, and further as appropriate to ensure adequate suppression.

    Children < 25 kg

    The recommended dose is 7.5 mg IM as a single dose repeated every 4 weeks. Increase dose if needed to the next available higher dose (e.g., 11.25 or 15 mg) at next monthly injection until total down-regulation is achieved. May adjust dose if changes in body weight occur. In clinical trials, patients receiving the 7.5 mg dosage ranged from 20.2 to 27 kg body weight. Monitor hormonal and clinical parameters at month 1 to 2, with dose changes, and further as appropriate to ensure adequate suppression.

    Once every 3 months regimen.
    NOTE: Do not use partial syringes or a combination of syringes to achieve a particular dose or to titrate dosages. Each 3-month depot syringe dose strength and formulation has different release characteristics.
    Intramuscular dosage (injection suspension, Lupron Depot-Ped 3-month)
    Children 2 to 11 years

    11.25 mg or 30 mg IM as a single dose repeated every 12 weeks (3 months). In order to ensure adequate suppression, monitor hormonal and clinical parameters at month 2 to 3, month 6, and further as judged clinically appropriate; in the case of inadequate suppression, consider other available GnRH agonists indicated for the treatment of central precocious puberty.

    Once daily regimen.
    Subcutaneous dosage (solution for injection)
    Children 1 to 12 years

    50 mcg/kg subcutaneous once daily. If response is not satisfactory, dosage may be titrated upward in 10 mcg/kg/day increments.

    For the preoperative treatment of anemia due to uterine leiomyomata (fibroids) in combination with iron supplementation when iron therapy alone fails to correct the anemia.
    Intramuscular dosage (injection suspension)
    Adults

    3.75 mg IM once monthly or 11.25 mg IM every 3 months in combination with supplemental iron therapy. The recommended duration of therapy is 3 months or less. Retreatment depends on return of symptoms.

    For the treatment of benign prostatic hyperplasia (BPH)†.
    Subcutaneous dosage (solution for injection)
    Adults

    In several trials, 1 mg subcutaneous once daily has been used. Because the condition is reversible if the drug is discontinued, therapy must be continuous.

    Intramuscular dosage (injection suspension)
    Adults

    A long-acting, depot formulation administered in a dosage of 3.75 mg IM once every 28 days for 24 weeks was effective. Because the condition is reversible if the drug is discontinued, therapy must be continuous.

    For the adjuvant treatment of premenopausal women with hormone receptor-positive breast cancer†.
    Subcutaneous dosage
    Adults

    11.25 mg subcutaneous once every 3 months for 2 years has been studied. In a study of 589 patients, leuprolide as compared to 6 cycles of CMF chemotherapy (cyclophosphamide/methotrexate/5-fluorouracil) was shown to be non-inferior for 2-year relapse free survival (63.9% vs. 63.4%, p = 0.83). An exploratory survival analysis favored leuprolide at 5 years (HR 1.5, 95% CI 1.13 to 1.99, p = 0.005).

    For the treatment of nonspecific symptoms associated with premenstrual syndrome (PMS)†.
    Subcutaneous dosage (solution for injection)
    Adults

    0.5 to 1 mg subcutaneous once daily has been shown to decrease symptoms associated with PMS. Because of the adverse reaction profile (e.g., osteoporosis, premature coronary artery disease), leuprolide is generally considered a third line agent in the treatment of PMS.

    For inhibiting premature leuteinizing hormone (LH) surges in women undergoing controlled ovarian hyperstimulation and subsequent in vitro fertilization (IVF) or other assisted reproductive technology (ART) for the treatment of infertility†.
    NOTE: Drugs such as ganirelix and cetrorelix are now more commonly used and are FDA-approved for this purpose. Leuprolide should only be used by a qualified infertility specialist. Withhold HCG administration in cases where the ovaries are abnormally enlarged to reduce the chance of inducing ovarian hyperstimulation syndrome (OHSS).
    Subcutaneous dosage for 'long-protocol' (leuprolide acetate injection solution only, do NOT use depot formulations)
    Adult females

    Optimal daily dosage is adjusted for the individual patient by the ART specialist; 'long-protocols' are most common but an alternative leuprolide 'flare protocol' is also used (not discussed here, note the dosage regimens for flare protocols are much different than those of long protocols). In the long protocol, leuprolide is typically started on day 21 to 24 of the menstrual cycle prior to the ovarian stimulation cycle; dosages vary but typically range 0.5 to 1 mg/day subcutaneous. Women will menstruate, continuing to use the leuprolide during oocyte stimulation with FSH, which usually begins after estradiol suppression is documented. By day 3 of the menstrual cycle, the dosage of leuprolide is typically decreased by 50%. Leuprolide and FSH (adjusting FSH dosage as needed) are administered until sufficient follicular development is attained. HCG is then administered to induce final follicular maturation for oocyte retrieval.

    For prevention of stuttering priapism† (i.e., recurrent priapism).
    Intramuscular dosage (injection suspension)
    Adults

    Case reports suggest standard monthly injections of 1.3 to 7.5 mg IM are effective. An 18-year old male with sickle cell anemia received 5.25 mg IM once monthly for 2 months, followed by 2.625 mg IM monthly for 6 months and then 1.3 mg IM monthly for 8 months; priapism did not recur during treatment and the patient continued to receive 1.3 mg IM monthly chronically. In another case report, a 32-year old male with idiopathic recurrent priapism received 7.5 mg IM once monthly for 2 months; priapism did not recur as of 4 months after discontinuing the leuprolide. Both patients achieved castration concentrations of testosterone. The American Urological Association recommends GnRH agonist therapy as a first-line option in the prevention of stuttering priapism; however, do not use leuprolide in patients who have not achieved full sexual maturation and adult stature. Additionally, even though patients experience a decrease in libido, most are able to engage in sexual activity.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Maximum dosage must be individualized and is dependent on formulation, indication, and patient response.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

    Renal Impairment

    Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

    ADMINISTRATION

     
    NOTE: The correct dose of leuprolide for the treatment of neoplastic disease will vary from protocol to protocol. Clinicians should consult the appropriate references to verify the dose.
     
    NOTE: Due to the similarity in packaging, dose strengths, and routes of administration for some leuprolide products, always verify the dosage form, product name, intent of use, population of use and other clinically distinguishing factors prior to administration in order to avoid medication errors.

    Injectable Administration

    Leuprolide is administered subcutaneously or intramuscularly depending upon the formulation.
    Injection sites should be rotated periodically.
    Visually inspect leuprolide acetate injection for particulate matter and discoloration prior to administration whenever solution and container permit.

    Intramuscular Administration

    Depot IM injection suspensions:
    NOTE: Take care to verify the correct product and intent of use prior to administration. Due to different release characteristics, Monthly, Three-Month, Four-Month, and Six-Month depot formulations are not equivalent at multiple or fractional doses; apparent equivalent doses from different formulations should not be given.
     
    Preparation:
    The powder should be visually inspected and the syringe should NOT BE USED if clumping or caking of the powder is evident. A thin layer of powder on the wall of the syringe is normal; the diluent supplied should appear clear.
    For the monthly, three (3) month, four (4) month, and six (6) month depot formulations: Use the diluent provided by the manufacturer. Screw the white plunger into the end stopper until the stopper begins to turn. Hold the syringe upright. Release the diluent by slowing pushing the plunger for 6—8 seconds, until the first stopper is at the blue line in the middle of the barrel. Keep the syringe upright.
    Gently mix the powder thoroughly to form a uniform suspension. The suspension should appear milky. If powder adheres to the stopper or caking/clumping is present, tap the syringe to disperse. DO NOT USE if any of the powder has not gone into suspension, as the patient may not receive an accurate dose.
    After reconstitution, the suspension settles very quickly; therefore, mix and administer the suspension immediately. Discard any suspension not used within 2 hours of reconstitution because it does not contain preservatives.
    Depot IM injection Administration:
    Clean the injection site with an alcohol swab prior to injection.
    Keeping the syringe upright, pull the needle cap upward without twisting, and advance the plunger to expel the air from the syringe. Insert the needle IM at a 90 degree angle and look for blood. If present, blood can be seen through the transparent LuproLoc safety device and would be visible just below the luer lock connection. Do not inject the medicine if blood is present. If no blood is present, administer the entire contents of the syringe IM.
    For the monthly 3.75 mg and the three (3) month 11.25 mg depot formulations: Insert the needle at a 90 degree angle into the gluteal area, anterior thigh, or deltoid.
    For all Depot-Ped formulations: Insert the needle at a 90 degree angle into the gluteal area, anterior thigh, or shoulder.
    After injection, withdraw the needle from the injection site. Immediately activate the LuproLoc safety device by pushing the arrow forward with the thumb or finger until the device is fully extended and a click is heard or felt.
    Be sure to rotate injection sites when dose is next due.

    Subcutaneous Administration

    Injection solutions:
    No dilution or reconstitution necessary.
    Inject appropriate dose subcutaneously.
    For patients who are self-administering leuprolide injection, make sure they are using the syringes provided by the manufacturer. If it is absolutely necessary to use a different syringe, only a 0.5-mL disposable, low-dose, U-100 insulin syringe should be used.
    Dosage preparation and subcutaneous depot administration (Eligard):
    Allow the product to reach room temperature before mixing. Once mixed, the product must be administered within 30 minutes.
    Prepare the 2 syringes for mixing per manufacturer's instructions. Join the two syringes together by pushing in and twisting until secure.
    Mix the product by pushing the contents of both syringes back and forth between the syringes (approximately 45 seconds) to obtain a uniform suspension. When thoroughly mixed, the suspension will appear a light tan to tan color. NOTE: The product must be mixed as described; shaking the product will not provide adequate mixing of the product.
    Hold syringes vertically with syringe B on the bottom. Draw the entire mixed product into syringe B (short, wide syringe) by depressing the syringe A plunger and slightly withdrawing the syringe B plunger. Uncouple syringe A while continuing to push down on the syringe A plunger. Small air bubbles will remain in the formulation and this is acceptable.
    Hold syringe B upright. Remove the pink cap on the bottom of the sterile needle cartridge. Attach the needle cartridge to the end of syringe B.
    Remove the clear needle cover prior to administration. Administer as a single dose subcutaneously.

    STORAGE

    Eligard:
    - Product in original packaging may be stored at room temperature (59 to 86 degrees F) for up to 8 weeks
    - Refrigerate (between 36 and 46 degrees F)
    Lupron:
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Do not freeze
    - Protect from light
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    - Store in carton until time of use
    Lupron Depot:
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    Lupron Depot-Ped:
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    Viadur:
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    Benzyl alcohol hypersensitivity

    Leuprolide injection contains benzyl alcohol; the depot formulation and implant do not. Patients who are allergic to benzyl alcohol may have an allergic reaction. Leuprolide subcutaneous injections should be used with caution in patients with known benzyl alcohol hypersensitivity.

    Gonadotropin-Releasing Hormone (GnRH) analogs hypersensitivity

    Leuprolide is contraindicated in patients with hypersensitivity to leuprolide, GnRH, or with Gonadotropin-Releasing Hormone (GnRH) Analogs hypersensitivity; anaphylactic reactions to synthetic GnRH or GnRH agonist analogs have been reported.

    Renal impairment, spinal cord compression, urinary tract obstruction

    Leuprolide may cause a sudden onset or worsening of prostate cancer or breast cancer symptoms (flare) due to transient increases in testosterone or estrogen levels, respectively, such as bone pain, neuropathy, hematuria, or urethral or bladder outlet obstruction. Patients with urinary tract obstruction or metastatic vertebral lesions should be monitored carefully for signs of renal impairment or spinal cord compression, respectively, during initial leuprolide treatment.

    Pituitary insufficiency

    Since leuprolide suppresses the pituitary-gonadal axis, diagnostic tests for pituitary insufficiency or other pituitary-gonadal function conducted during treatment and after cessation of therapy may be misleading.

    Dysfunctional uterine bleeding, menstruation, vaginal bleeding

    Leuprolide therapy interrupts menstruation; women who continue to cycle or who experience breakthrough bleeding while receiving leuprolide should notify their physician. The drug should not be administered to women with dysfunctional uterine bleeding or undiagnosed vaginal bleeding.

    Children, geriatric, osteoporosis

    Leuprolide should be used with caution in patients with osteoporosis. GnRH analog therapy increases the risk of reduced bone mineral density in men as well as women, and may have particular relevance for the geriatric population. The addition of hormone replacement therapy (estrogens and/or progestins) to leuprolide therapy for endometriosis or uterine fibroids may be effective in reducing the bone mineral loss in women. Reduced bone mineral density and osteopenia are also a concern if GnRH or LHRH analogs are used in adolescent children. LHRH-analogs (aka GnRH analogs) have been used alone or added to growth hormone (rh-GH) therapy to moderately increase adult height in adolescents with normally timed puberty and idiopathic short stature; the LHRH-analogs delay puberty and thus prolong the period of bone growth via delay of sex hormone-induced growth-plate senescence. In one study, the use of a LHRH-agonist for 4 years, the typical duration needed to see an increase in adult height, was found to decrease bone mineral density in the lumbosacral region to more than 1 standard deviation below the population mean in 82% of adolescent patients receiving the LHRH-agonist (see Adverse Reactions). The authors concluded that LHRH-agonist therapy cannot be routinely recommended to augment height in short adolescents with normally timed puberty; for most adolescents the potential benefit of treatment would not outweigh the risks. Leuprolide should not be used for the treatment of stuttering priapism in adolescents or children who have not yet reached full sexual maturity or adult stature. Prescribers must use caution and be sure to select the appropriate product for use in pediatric patients. While the Lupron Depot-Ped product is indicated for use in children, the Viadur implant and Eligard brands of leuprolide are contraindicated in children and adolescents due to limited experience.

    Females, pregnancy

    Although leuprolide has been used as an adjunct in fertility protocols, leuprolide is contraindicated during pregnancy because spontaneous abortion could occur once conception ensues (FDA pregnancy category X). The Viadur implant and Eligard brands of leuprolide are contraindicated in females due to limited experience and lack of indication for use.

    Breast-feeding

    Because the consequences to the nursing infant are not known, breast-feeding should be avoided during treatment with leuprolide. The Viadur implant and Eligard brands of leuprolide are contraindicated in females due to due to a lack of indication for use and limited experience, thus these products would not be given to the lactating female.

    Cardiac disease, hypercholesterolemia, hypertension, myocardial infarction, obesity, stroke, tobacco smoking

    The use of GnRH analogs in men has been reported in association with an increased risk of myocardial infarction, sudden cardiac death, and stroke. Carefully weigh the known benefits and risks of GnRH agonists such as leuprolide when determining appropriate treatment for prostate cancer. Also, monitor patients for signs and symptoms suggestive of the development of cardiovascular disease. The risk of myocardial infarction, sudden cardiac death, and stroke appears low but needs to be evaluated carefully along with cardiovascular risk factors like cardiac disease, tobacco smoking, hypertension, hypercholesterolemia, and obesity. Manage patients according to current clinical practice. At this time, there are no known comparable studies evaluating the risk of cardiovascular events in women or children taking GnRH agonists for other indications.

    Diabetes mellitus, hyperglycemia

    The use of GnRH analogs in men has been reported in association with hyperglycemia and an increased risk of developing diabetes mellitus. Carefully weigh the known benefits and risks of GnRH agonists such as leuprolide when determining appropriate treatment for prostate cancer. Periodically monitor patients' blood glucose concentration and/or glycosylated hemoglobin; hyperglycemia may represent diabetes mellitus development or worsening of glycemic control in patients with the condition. Manage patients according to current clinical practice. At this time, there are no known comparable studies evaluating the risk of diabetes in women or children taking GnRH agonists for other indications.

    Alcoholism, cardiac arrhythmias, coronary artery disease, heart failure, hepatic disease, hypocalcemia, hypokalemia, hypomagnesemia, long QT syndrome, malnutrition, QT prolongation, thyroid disease

    Androgen deprivation therapy prolongs the QT interval. Consider whether the benefits of androgen deprivation treatments (e.g., leuprolide) outweigh the potential risk for QT prolongation in patients with congenital long QT syndrome, electrolyte imbalance (e,g., hypokalemia, hypomagnesemia, hypocalcemia), or congestive heart failure. Also use with caution in patients with cardiac disease or other conditions that may increase the risk of QT prolongation including cardiac arrhythmias, bradycardia, myocardial infarction, hypertension, coronary artery disease, or in patients receiving medications known to prolong the QT interval or cause electrolyte imbalances. Females, geriatric patients, patients with diabetes mellitus, thyroid disease, malnutrition, alcoholism, or hepatic disease may also be at increased risk for QT prolongation. . Consider periodic monitoring of electrocardiogram (ECG) and electrolytes.

    Brain tumor, cerebrovascular disease, seizure disorder

    Use leuprolide with caution in patients with a preexisting seizure disorder. Seizures have been reported during postmarketing surveillance in patients with a history of epilepsy, cerebrovascular disease, central nervous system anomalies or brain tumor, and patients on concomitant medications that have been associated with seizures. Seizures have also been reported in patients without any risk factors.

    Depression, suicidal ideation

    Use leuprolide with caution in patients with depression and emotional instability; monitor patients for worsening of psychiatric symptoms during treatment with leuprolide. During postmarketing experience, emotional lability, such as crying, irritability, impatience, anger, and aggression were reported. Depression, including rare reports of suicidal ideation and attempt, were reported in children treated for central precocious puberty. Many, but not all, of these patients had a history of psychiatric illness or other comorbidities with an increased risk of depression.

    ADVERSE REACTIONS

    Severe

    renal tubular obstruction / Delayed / 0-5.0
    epididymitis / Delayed / 0-5.0
    seizures / Delayed / 0-5.0
    visual impairment / Early / 0-5.0
    GI obstruction / Delayed / 0-5.0
    peptic ulcer / Delayed / 0-5.0
    GI bleeding / Delayed / 0-5.0
    bone fractures / Delayed / 0-5.0
    atrial fibrillation / Early / 0-5.0
    myocardial infarction / Delayed / 0-5.0
    arrhythmia exacerbation / Early / 0-5.0
    heart failure / Delayed / 0-5.0
    pulmonary embolism / Delayed / 0-5.0
    bradycardia / Rapid / 0-5.0
    thromboembolism / Delayed / 0-5.0
    pleural effusion / Delayed / 0-5.0
    pulmonary edema / Early / 0-5.0
    pulmonary fibrosis / Delayed / 0-5.0
    feminization / Delayed / 0-2.0
    thrombosis / Delayed / 2.0-2.0
    anaphylactoid reactions / Rapid / 0-0.1
    erythema multiforme / Delayed / 0-0.1
    muscle paralysis / Delayed / Incidence not known
    hearing loss / Delayed / Incidence not known
    suicidal ideation / Delayed / Incidence not known
    rectal fistula / Delayed / Incidence not known
    ovarian hyperstimulation syndrome (OHSS) / Delayed / Incidence not known
    pituitary apoplexy / Early / Incidence not known
    stroke / Early / Incidence not known

    Moderate

    hot flashes / Early / 8.3-73.3
    edema / Delayed / 0-20.8
    testicular atrophy / Delayed / 0-20.2
    peripheral edema / Delayed / 0-12.0
    constipation / Delayed / 0-9.9
    dehydration / Delayed / 0-8.2
    hypertension / Early / 0-8.0
    hematuria / Delayed / 0-6.0
    impotence (erectile dysfunction) / Delayed / 0-5.4
    depression / Delayed / 0-5.3
    anemia / Delayed / 0-5.0
    peripheral neuropathy / Delayed / 0-5.0
    hyperesthesia / Delayed / 0-5.0
    bone pain / Delayed / 0-5.0
    bladder spasm / Early / 0-5.0
    dysuria / Early / 0-5.0
    urinary incontinence / Early / 0-5.0
    memory impairment / Delayed / 0-5.0
    amnesia / Delayed / 0-5.0
    confusion / Early / 0-5.0
    amblyopia / Delayed / 0-5.0
    blurred vision / Early / 0-5.0
    hepatomegaly / Delayed / 0-5.0
    dysphagia / Delayed / 0-5.0
    impaired wound healing / Delayed / 0-5.0
    diabetes mellitus / Delayed / 0-5.0
    lymphadenopathy / Delayed / 0-5.0
    hypotension / Rapid / 0-5.0
    angina / Early / 0-5.0
    dysphonia / Delayed / 0-5.0
    hypoxia / Early / 0-5.0
    hemoptysis / Delayed / 0-5.0
    urinary retention / Early / 0-4.6
    vaginitis / Delayed / 3.0-3.0
    vaginal bleeding / Delayed / 3.0-3.0
    skin ulcer / Delayed / 0-3.0
    colitis / Delayed / 2.5-2.5
    goiter / Delayed / 0-2.0
    growth inhibition / Delayed / 0-2.0
    myopathy / Delayed / 0-2.0
    phlebitis / Rapid / 2.0-2.0
    dyspnea / Early / 2.0-2.0
    hyperphosphatemia / Delayed / 5.0
    hyperuricemia / Delayed / 5.0
    hyperglycemia / Delayed / 5.0
    hyperlipidemia / Delayed / 5.0
    leukopenia / Delayed / 5.0
    eosinophilia / Delayed / 5.0
    prostate pain / Delayed / Incidence not known
    hypokalemia / Delayed / Incidence not known
    pyuria / Delayed / Incidence not known
    hyperreflexia / Delayed / Incidence not known
    euphoria / Early / Incidence not known
    hallucinations / Early / Incidence not known
    elevated hepatic enzymes / Delayed / Incidence not known
    hepatitis / Delayed / Incidence not known
    erythema / Early / Incidence not known
    hematoma / Early / Incidence not known
    secondary malignancy / Delayed / Incidence not known
    ovarian enlargement / Delayed / Incidence not known
    osteopenia / Delayed / Incidence not known
    osteoporosis / Delayed / Incidence not known
    synovitis / Delayed / Incidence not known
    palpitations / Early / Incidence not known
    sinus tachycardia / Rapid / Incidence not known
    QT prolongation / Rapid / Incidence not known
    wheezing / Rapid / Incidence not known
    thrombocytopenia / Delayed / Incidence not known

    Mild

    injection site reaction / Rapid / 0-37.5
    ecchymosis / Delayed / 0-34.6
    musculoskeletal pain / Early / 0-32.7
    fatigue / Early / 0-17.5
    asthenia / Delayed / 0-12.2
    skin irritation / Early / 0-12.2
    infection / Delayed / 0-12.2
    headache / Early / 0-10.2
    arthralgia / Delayed / 0-9.3
    insomnia / Early / 0-8.5
    dizziness / Early / 0-8.3
    paresthesias / Delayed / 0-8.2
    myalgia / Early / 0-8.2
    mastalgia / Delayed / 3.1-7.0
    gynecomastia / Delayed / 2.2-7.0
    cough / Delayed / 1.3-6.6
    increased urinary frequency / Early / 2.2-6.0
    urinary urgency / Early / 0-6.0
    anorexia / Delayed / 0-6.0
    libido decrease / Delayed / 3.3-5.4
    hyperhidrosis / Delayed / 0-5.3
    breast enlargement / Delayed / 0-5.0
    syncope / Early / 0-5.0
    parosmia / Delayed / 0-5.0
    agitation / Early / 0-5.0
    lethargy / Early / 0-5.0
    emotional lability / Early / 0-5.0
    anxiety / Delayed / 0-5.0
    xerophthalmia / Early / 0-5.0
    tinnitus / Delayed / 0-5.0
    dysgeusia / Early / 0-5.0
    appetite stimulation / Delayed / 0-5.0
    diarrhea / Early / 0-5.0
    vomiting / Early / 0-5.0
    gingivitis / Delayed / 0-5.0
    weight loss / Delayed / 0-5.0
    nausea / Early / 0-5.0
    xerostomia / Early / 0-5.0
    skin hyperpigmentation / Delayed / 0-5.0
    xerosis / Delayed / 0-5.0
    melasma / Delayed / 0-5.0
    alopecia / Delayed / 0-5.0
    ptosis / Delayed / 0-5.0
    muscle cramps / Delayed / 0-5.0
    fever / Early / 0-5.0
    chills / Rapid / 0-5.0
    hiccups / Early / 0-5.0
    epistaxis / Delayed / 0-5.0
    testicular pain / Early / 3.8-3.8
    nocturia / Early / 0-3.8
    weakness / Early / 3.6-3.6
    night sweats / Early / 2.7-3.3
    vaginal discharge / Delayed / 3.0-3.0
    rash (unspecified) / Early / 0-3.0
    seborrhea / Delayed / 3.0-3.0
    weight gain / Delayed / 0-2.3
    dysmenorrhea / Delayed / 0-2.0
    back pain / Delayed / 0-2.0
    malaise / Early / 0-2.0
    vertigo / Early / 0-2.0
    abdominal pain / Early / 0-2.0
    flatulence / Early / 0-2.0
    dyspepsia / Early / 0-2.0
    purpura / Delayed / 0-2.0
    skin hypopigmentation / Delayed / 0-2.0
    photosensitivity / Delayed / 0-0.1
    urticaria / Rapid / 0-0.1
    eructation / Early / 5.0
    amenorrhea / Delayed / Incidence not known
    libido increase / Delayed / Incidence not known
    hyporeflexia / Delayed / Incidence not known
    tremor / Early / Incidence not known
    acneiform rash / Delayed / Incidence not known
    influenza / Delayed / Incidence not known
    rhinitis / Early / Incidence not known
    pharyngitis / Delayed / Incidence not known
    sinusitis / Delayed / Incidence not known
    nasal congestion / Early / Incidence not known
    rhinorrhea / Early / Incidence not known

    DRUG INTERACTIONS

    Abarelix: (Major) These drugs are duplicate therapies and thus would not be used together. Additionally, Androgen deprivation therapy (e.g., leuprolide or abarelix) may prolong the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Because of the potential for QT prolongation and torsade de pointes (TdP), use of these drugs together should be avoided.
    Albuterol: (Minor) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with leuprolide include beta-agonists.
    Albuterol; Ipratropium: (Minor) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with leuprolide include beta-agonists.
    Alfuzosin: (Major) Based on electrophysiology studies performed by the manufacturer, alfuzosin has a slight effect to prolong the QT interval. The QT prolongation appeared less with alfuzosin 10 mg than with 40 mg. The manufacturer warns that the QT effect of alfuzosin should be considered prior to administering the drug to patients taking other medications known to prolong the QT interval. Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Use these drugs together cautiously and with close monitoring.
    Amiodarone: (Major) Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). The concomitant use of amiodarone and other drugs known to prolong the QT interval should only be done after careful assessment of risks versus benefits. If possible, avoid coadministration of amiodarone and drugs known to prolong the QT interval. Due to the extremely long half-life of amiodarone , a drug interaction is possible for days to weeks after discontinuation of amiodarone. Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Use with caution and with close clinical monitoring with amiodarone.
    Amitriptyline: (Minor) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with leuprolide include tricyclic antidepressants. Tricyclic antidepressants (TCAs) share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations).
    Amitriptyline; Chlordiazepoxide: (Minor) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with leuprolide include tricyclic antidepressants. Tricyclic antidepressants (TCAs) share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations).
    Amoxicillin; Clarithromycin; Lansoprazole: (Major) Clarithromycin is associated with an established risk for QT prolongation and torsades de pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with clarithromycin include leuprolide. Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval.
    Amoxicillin; Clarithromycin; Omeprazole: (Major) Clarithromycin is associated with an established risk for QT prolongation and torsades de pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with clarithromycin include leuprolide. Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval.
    Anagrelide: (Moderate) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with leuprolide include anagrelide.
    Androgens: (Major) Leuprolide inhibits steroidogenesis. While no drug interactions have been reported with leuprolide, therapy with androgens would be relatively contraindicated and would counteract the therapeutic effect of leuprolide.
    Anthracyclines: (Moderate) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Leuprolide should be used with caution with cardiotoxic drugs. Acute cardiotoxicity can occur during administration of daunorubicin, doxorubicin, epirubicin, or idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Apomorphine: (Major) Limited data indicate that QT prolongation is possible with apomorphine administration; the change in QTc interval is not significant in most patients receiving dosages within the manufacturer's guidelines. In one study, a single mean dose of 5.2 mg (range 2 to 10 mg) prolonged the QT interval by about 3 msec. However, large increases (> 60 msecs from pre-dose) have occurred in two patients receiving 6 mg doses. Doses <= 6 mg SC are associated with minimal increases in QTc; doses > 6 mg SC do not provide additional clinical benefit and are not recommended. Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval. This effect may be additive to other drugs that may cause QT prolongation.
    Arformoterol: (Moderate) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with leuprolide include beta-agonists.
    Aripiprazole: (Moderate) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with leuprolide include aripiprazole.
    Arsenic Trioxide: (Major) If possible, drugs that are known to prolong the QT interval should be discontinued prior to initiating arsenic trioxide therapy. QT prolongation should be expected with the administration of arsenic trioxide. ECG monitoring is recommended during use. Torsade de pointes (TdP) and complete atrioventricular block have been reported. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with arsenic trioxide include leuprolide Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval.
    Artemether; Lumefantrine: (Major) The administration of artemether is associated with prolongation of the QT interval. Although there are no studies examining the effects of artemether in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation and should be avoided. Consider ECGs and close clinical monitoring if co-use of such drugs is medically necessary. Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use artemether. (Major) The administration of lumefantrine is associated with prolongation of the QT interval. Although there are no studies examining the effects of lumefantrine in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation and should be avoided. Consider ECGs and close clinical monitoring if co-use of such drugs is medically necessary. Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use lumefantrine.
    Asenapine: (Major) 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. Drugs with a possible risk for QT prolongation and torsade de pointes (TdP) that should be avoided in combination with asenapine include leuprolide. Androgen deprivation therapy prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Asenapine might also decrease the clinical response to leuprolide. Antipsychotic-induced hyperprolactinemia results in down-regulatation of the number of pituitary GnRH receptors and may interfere with the response to any of the gonadotropin-releasing hormone (GnRH) analogs (e.g., leuprolide).
    Atomoxetine: (Moderate) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with leuprolide include atomoxetine. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose. Atomoxetine is also considered a drug with a possible risk of TdP.
    Azithromycin: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), azithromycin and leuprolide should be used together cautiously. There have been case reports of QT prolongation and TdP with the use of azithromycin in postmarketing reports. Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval.
    Bedaquiline: (Major) Bedaquiline has been reported to prolong the QT interval. 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. Coadministration with other QT prolonging drugs may result in additive or synergistic prolongation of the QT interval; avoid such agents if possible. Drugs with a possible risk for QT prolongation and torsade de pointes (TdP) that should be used cautiously and with close monitoring with bedaquiline include leuprolide. Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval.
    Bepridil: (Severe) Bepridil has Class I antiarrhythmic properties and is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Patients receiving other drugs which have the potential for QT prolongation have an increased risk of developing proarrhythmias during bepridil therapy. According to the manufacturer, bepridil is contraindicated for use with drugs that prolong the QT interval due to the risk of TdP. Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Because of the potential for TdP, use of bepridil with leuprolide is contraindicated.
    Bretylium: (Severe) The use of bretylium in conjunction with drugs associated with QT prolongation should be used with extreme caution due to the potential risk for ventricular tachycardia, including torsade de pointes (TdP). Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Because of the potential for TdP, use of bretylium with leuprolide is contraindicated.
    Budesonide; Formoterol: (Moderate) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with leuprolide include beta-agonists.
    Buprenorphine: (Major) Buprenorphine should be used cautiously and with close monitoring with leuprolide. Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval. Buprenorphine has also been associated with QT prolongation and has a possible risk of torsade de pointes (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, such as leuprolide. If these drugs are used together, consider the potential for additive effects on the QT interval.
    Buprenorphine; Naloxone: (Major) Buprenorphine should be used cautiously and with close monitoring with leuprolide. Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval. Buprenorphine has also been associated with QT prolongation and has a possible risk of torsade de pointes (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, such as leuprolide. If these drugs are used together, consider the potential for additive effects on the QT interval.
    Ceritinib: (Major) Periodically monitor electrolytes and ECGs in patients receiving concomitant treatment with ceritinib and leuprolide; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent prolongation of the QT interval. Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval.
    Chloroquine: (Major) Chloroquine administration is associated with an increased risk of QT prolongation and torsades de pointes (TdP). The need to coadminister chloroquine with drugs known to prolong the QT interval should be done with a careful assessment of risks versus benefits and should be avoided when possible. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with chloroquine include leuprolide. Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval.
    Chlorpromazine: (Major) Androgen-deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with other medications that prolong the QT interval, such as the phenothiazines. Phenothiazines have been associated with a risk of QT prolongation and/or torsade de pointes (TdP). This risk is generally higher at elevated drugs concentrations of phenothiazines. Chlorpromazine is specifically associated with an established risk of QT prolongation and TdP ; case reports have included patients receiving therapeutic doses of chlorpromazine. Agents that prolong the QT interval could lead to torsade de pointes when combined with a phenothiazine, and therefore are generally not recommended for combined use; if they must be used, use with caution and with close monitoring. Also, drugs that cause hyperprolactinemia, such as antipsychotics, should be used with caution with gonadotropin releasing hormone (GnRH) analogs (e.g., leuprolide, others) since hyperprolactinemia downregulates the number of pituitary GnRH receptors.
    Cimetidine: (Minor) In the absence of relevant data and as a precaution, drugs that cause hyperprolactinemia, such as cimetidine, should not be administered concomitantly with gonadotropin releasing hormone analogs since hyperprolactinemia down-regulates the number of pituitary GnRH receptors.
    Ciprofloxacin: (Moderate) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with leuprolide include ciprofloxacin.
    Cisapride: (Severe) QT prolongation and ventricular arrhythmias, including torsade de pointes (TdP) and death, have been reported with cisapride. Because of the potential for TdP, cisapride is contraindicated with medications that may prolong the QT interval. Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Because of the potential for TdP, use of cisapride with leuprolide is contraindicated.
    Citalopram: (Major) Citalopram causes dose-dependent QT interval prolongation. According to the manufacturer, 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. Drugs with a possible risk for QT prolongation that should be used cautiously and with close monitoring with citalopram include leuprolide. Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval.
    Clarithromycin: (Major) Clarithromycin is associated with an established risk for QT prolongation and torsades de pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with clarithromycin include leuprolide. Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval.
    Clomipramine: (Minor) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with leuprolide include tricyclic antidepressants. Tricyclic antidepressants (TCAs) share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations).
    Clozapine: (Major) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Treatment with clozapine has been associated with QT prolongation, torsade de pointes (TdP), cardiac arrest, and sudden death. The manufacturer of clozapine recommends caution during concurrent use with medications known to cause QT prolongation. Additionally, antipsychotic-induced hyperprolactinemia results in down-regulatation of the number of pituitary GnRH receptors and may interfere with the response to leuprolide therapy; however, in contrast to most typical antipsychotics, clozapine is not often associated with hyperprolactinemia.
    Codeine; Phenylephrine; Promethazine: (Moderate) Androgen-deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with other medications that prolong the QT interval, such as the phenothiazines. Promethazine (a phenothiazine antiemetic and antihistamine) carries a possible risk of QT prolongation. Drugs with a possible risk for QT prolongation and TdP should be used cautiously together.
    Codeine; Promethazine: (Moderate) Androgen-deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with other medications that prolong the QT interval, such as the phenothiazines. Promethazine (a phenothiazine antiemetic and antihistamine) carries a possible risk of QT prolongation. Drugs with a possible risk for QT prolongation and TdP should be used cautiously together.
    Conjugated Estrogens: (Major) Concomitant use of estrogens with GnRH analogs is relatively contraindicated, as estrogens could counteract the therapeutic effect of GnRH analogs for various hormone-sensitive conditions. In the rare cases that these drugs are used together, close clinical monitoring for the desired clinical and hormonal response is necessary.
    Conjugated Estrogens; Bazedoxifene: (Major) Concomitant use of estrogens with GnRH analogs is relatively contraindicated, as estrogens could counteract the therapeutic effect of GnRH analogs for various hormone-sensitive conditions. In the rare cases that these drugs are used together, close clinical monitoring for the desired clinical and hormonal response is necessary.
    Conjugated Estrogens; Medroxyprogesterone: (Major) Concomitant use of estrogens with GnRH analogs is relatively contraindicated, as estrogens could counteract the therapeutic effect of GnRH analogs for various hormone-sensitive conditions. In the rare cases that these drugs are used together, close clinical monitoring for the desired clinical and hormonal response is necessary.
    Crizotinib: (Major) Monitor ECGs for QT prolongation and monitor electrolytes in patients receiving crizotinib concomitantly with leuprolide. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary for crizotinib patients if QT prolongation occurs. Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Crizotinib has also been associated with concentration-dependent QT prolongation.
    Cyclobenzaprine: (Moderate) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with leuprolide include cyclobenzaprine.
    Danazol: (Major) Leuprolide inhibits steroidogenesis. While no drug interactions have been reported with leuprolide, therapy with androgens would be relatively contraindicated and would counteract the therapeutic effect of leuprolide.
    Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Major) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with leuprolide include ritonavir.
    Dasatinib: (Major) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with leuprolide include dasatinib.
    Daunorubicin: (Moderate) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Leuprolide should be used with caution with cardiotoxic drugs. Acute cardiotoxicity can occur during administration of daunorubicin, doxorubicin, epirubicin, or idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Degarelix: (Major) It is not common for these two agents to be used together at the same time, due to duplicate effects on hormone regulation. Androgen deprivation therapy (e.g., leuprolide, degarelix) prolongs the QT interval; the risk may be increased with concurrent use.
    Desflurane: (Major) Halogenated anesthetics are associated with a risk for QT prolongation and potential cardiac arrhythmias. Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Halogenated anesthetics should be used cautiously and with close monitoring in patients receiving leuprolide.
    Desipramine: (Minor) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with leuprolide include tricyclic antidepressants. Tricyclic antidepressants (TCAs) share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations).
    Deutetrabenazine: (Moderate) For patients taking a deutetrabenazine dosage more than 24 mg/day with leuprolide, assess the QTc interval before and after increasing the dosage of either medication. Clinically relevant QTc prolongation may occur with deutetrabenazine. Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval.
    Dextromethorphan; Promethazine: (Moderate) Androgen-deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with other medications that prolong the QT interval, such as the phenothiazines. Promethazine (a phenothiazine antiemetic and antihistamine) carries a possible risk of QT prolongation. Drugs with a possible risk for QT prolongation and TdP should be used cautiously together.
    Dextromethorphan; Quinidine: (Major) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Quinidine is associated with QT prolongation and torsades de pointes (TdP).
    Dienogest; Estradiol valerate: (Major) Concomitant use of estrogens with GnRH analogs is relatively contraindicated, as estrogens could counteract the therapeutic effect of GnRH analogs for various hormone-sensitive conditions. In the rare cases that these drugs are used together, close clinical monitoring for the desired clinical and hormonal response is necessary.
    Diethylstilbestrol, DES: (Major) Concomitant use of estrogens with GnRH analogs is relatively contraindicated, as estrogens could counteract the therapeutic effect of GnRH analogs for various hormone-sensitive conditions. In the rare cases that these drugs are used together, close clinical monitoring for the desired clinical and hormonal response is necessary.
    Disopyramide: (Major) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with leuprolide include disopyramide.
    Dofetilide: (Severe) Dofetilide, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Because of the potential for TdP, dofetilide is contraindicated with any drugs associated with QT prolongation. Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Because of the potential for TdP, use of dofetilide with leuprolide is contraindicated.
    Dolasetron: (Major) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with leuprolide include dolasetron.
    Donepezil: (Moderate) Donepezil should be used cautiously and with close monitoring with leuprolide. Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. 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.
    Donepezil; Memantine: (Moderate) Donepezil should be used cautiously and with close monitoring with leuprolide. Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. 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.
    Doxepin: (Minor) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with leuprolide include tricyclic antidepressants. Tricyclic antidepressants (TCAs) share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations).
    Doxorubicin: (Moderate) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Leuprolide should be used with caution with cardiotoxic drugs. Acute cardiotoxicity can occur during administration of daunorubicin, doxorubicin, epirubicin, or idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Dronedarone: (Severe) 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. Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Because of the potential for TdP, use of dronedarone with leuprolide is contraindicated.
    Droperidol: (Major) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with leuprolide include droperidol.
    Drospirenone; Estradiol: (Major) Concomitant use of estrogens with GnRH analogs is relatively contraindicated, as estrogens could counteract the therapeutic effect of GnRH analogs for various hormone-sensitive conditions. In the rare cases that these drugs are used together, close clinical monitoring for the desired clinical and hormonal response is necessary.
    Drospirenone; Ethinyl Estradiol: (Major) Concomitant use of estrogens with GnRH analogs is relatively contraindicated, as estrogens could counteract the therapeutic effect of GnRH analogs for various hormone-sensitive conditions. In the rare cases that these drugs are used together, close clinical monitoring for the desired clinical and hormonal response is necessary.
    Drospirenone; Ethinyl Estradiol; Levomefolate: (Major) Concomitant use of estrogens with GnRH analogs is relatively contraindicated, as estrogens could counteract the therapeutic effect of GnRH analogs for various hormone-sensitive conditions. In the rare cases that these drugs are used together, close clinical monitoring for the desired clinical and hormonal response is necessary.
    Efavirenz: (Major) Although data are limited, coadministration of efavirenz and leuprolide may increase the risk for QT prolongation and torsade de pointes (TdP). QT prolongation has been observed with use of efavirenz. Androgen deprivation therapy (e.g., leuprolide) also prolongs the QT interval.
    Efavirenz; Emtricitabine; Tenofovir: (Major) Although data are limited, coadministration of efavirenz and leuprolide may increase the risk for QT prolongation and torsade de pointes (TdP). QT prolongation has been observed with use of efavirenz. Androgen deprivation therapy (e.g., leuprolide) also prolongs the QT interval.
    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 leuprolide (including leuprolide; norethindrone).
    Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Major) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with leuprolide include rilpivirine.
    Emtricitabine; Rilpivirine; Tenofovir disoproxil fumarate: (Major) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with leuprolide include rilpivirine.
    Enflurane: (Major) Halogenated anesthetics are associated with a risk for QT prolongation and potential cardiac arrhythmias. Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Halogenated anesthetics should be used cautiously and with close monitoring in patients receiving leuprolide.
    Epirubicin: (Moderate) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Leuprolide should be used with caution with cardiotoxic drugs. Acute cardiotoxicity can occur during administration of daunorubicin, doxorubicin, epirubicin, or idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Eribulin: (Major) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with leuprolide include eribulin.
    Erythromycin: (Major) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with leuprolide include erythromycin.
    Erythromycin; Sulfisoxazole: (Major) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with leuprolide include erythromycin.
    Escitalopram: (Moderate) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with leuprolide include escitalopram.
    Esterified Estrogens: (Major) Concomitant use of estrogens with GnRH analogs is relatively contraindicated, as estrogens could counteract the therapeutic effect of GnRH analogs for various hormone-sensitive conditions. In the rare cases that these drugs are used together, close clinical monitoring for the desired clinical and hormonal response is necessary.
    Esterified Estrogens; Methyltestosterone: (Major) Concomitant use of estrogens with GnRH analogs is relatively contraindicated, as estrogens could counteract the therapeutic effect of GnRH analogs for various hormone-sensitive conditions. In the rare cases that these drugs are used together, close clinical monitoring for the desired clinical and hormonal response is necessary. (Major) Leuprolide inhibits steroidogenesis. While no drug interactions have been reported with leuprolide, therapy with androgens would be relatively contraindicated and would counteract the therapeutic effect of leuprolide.
    Estradiol Cypionate; Medroxyprogesterone: (Major) Concomitant use of estrogens with GnRH analogs is relatively contraindicated, as estrogens could counteract the therapeutic effect of GnRH analogs for various hormone-sensitive conditions. In the rare cases that these drugs are used together, close clinical monitoring for the desired clinical and hormonal response is necessary.
    Estradiol: (Major) Concomitant use of estrogens with GnRH analogs is relatively contraindicated, as estrogens could counteract the therapeutic effect of GnRH analogs for various hormone-sensitive conditions. In the rare cases that these drugs are used together, close clinical monitoring for the desired clinical and hormonal response is necessary.
    Estradiol; Levonorgestrel: (Major) Concomitant use of estrogens with GnRH analogs is relatively contraindicated, as estrogens could counteract the therapeutic effect of GnRH analogs for various hormone-sensitive conditions. In the rare cases that these drugs are used together, close clinical monitoring for the desired clinical and hormonal response is necessary.
    Estradiol; Norethindrone: (Major) Concomitant use of estrogens with GnRH analogs is relatively contraindicated, as estrogens could counteract the therapeutic effect of GnRH analogs for various hormone-sensitive conditions. In the rare cases that these drugs are used together, close clinical monitoring for the desired clinical and hormonal response is necessary.
    Estradiol; Norgestimate: (Major) Concomitant use of estrogens with GnRH analogs is relatively contraindicated, as estrogens could counteract the therapeutic effect of GnRH analogs for various hormone-sensitive conditions. In the rare cases that these drugs are used together, close clinical monitoring for the desired clinical and hormonal response is necessary.
    Estrogens: (Major) Concomitant use of estrogens with GnRH analogs is relatively contraindicated, as estrogens could counteract the therapeutic effect of GnRH analogs for various hormone-sensitive conditions. In the rare cases that these drugs are used together, close clinical monitoring for the desired clinical and hormonal response is necessary.
    Estropipate: (Major) Concomitant use of estrogens with GnRH analogs is relatively contraindicated, as estrogens could counteract the therapeutic effect of GnRH analogs for various hormone-sensitive conditions. In the rare cases that these drugs are used together, close clinical monitoring for the desired clinical and hormonal response is necessary.
    Ethinyl Estradiol: (Major) Concomitant use of estrogens with GnRH analogs is relatively contraindicated, as estrogens could counteract the therapeutic effect of GnRH analogs for various hormone-sensitive conditions. In the rare cases that these drugs are used together, close clinical monitoring for the desired clinical and hormonal response is necessary.
    Ethinyl Estradiol; Desogestrel: (Major) Concomitant use of estrogens with GnRH analogs is relatively contraindicated, as estrogens could counteract the therapeutic effect of GnRH analogs for various hormone-sensitive conditions. In the rare cases that these drugs are used together, close clinical monitoring for the desired clinical and hormonal response is necessary.
    Ethinyl Estradiol; Ethynodiol Diacetate: (Major) Concomitant use of estrogens with GnRH analogs is relatively contraindicated, as estrogens could counteract the therapeutic effect of GnRH analogs for various hormone-sensitive conditions. In the rare cases that these drugs are used together, close clinical monitoring for the desired clinical and hormonal response is necessary.
    Ethinyl Estradiol; Etonogestrel: (Major) Concomitant use of estrogens with GnRH analogs is relatively contraindicated, as estrogens could counteract the therapeutic effect of GnRH analogs for various hormone-sensitive conditions. In the rare cases that these drugs are used together, close clinical monitoring for the desired clinical and hormonal response is necessary.
    Ethinyl Estradiol; Levonorgestrel: (Major) Concomitant use of estrogens with GnRH analogs is relatively contraindicated, as estrogens could counteract the therapeutic effect of GnRH analogs for various hormone-sensitive conditions. In the rare cases that these drugs are used together, close clinical monitoring for the desired clinical and hormonal response is necessary.
    Ethinyl Estradiol; Levonorgestrel; Folic Acid; Levomefolate: (Major) Concomitant use of estrogens with GnRH analogs is relatively contraindicated, as estrogens could counteract the therapeutic effect of GnRH analogs for various hormone-sensitive conditions. In the rare cases that these drugs are used together, close clinical monitoring for the desired clinical and hormonal response is necessary.
    Ethinyl Estradiol; Norelgestromin: (Major) Concomitant use of estrogens with GnRH analogs is relatively contraindicated, as estrogens could counteract the therapeutic effect of GnRH analogs for various hormone-sensitive conditions. In the rare cases that these drugs are used together, close clinical monitoring for the desired clinical and hormonal response is necessary.
    Ethinyl Estradiol; Norethindrone Acetate: (Major) Concomitant use of estrogens with GnRH analogs is relatively contraindicated, as estrogens could counteract the therapeutic effect of GnRH analogs for various hormone-sensitive conditions. In the rare cases that these drugs are used together, close clinical monitoring for the desired clinical and hormonal response is necessary.
    Ethinyl Estradiol; Norethindrone Acetate; Ferrous fumarate: (Major) Concomitant use of estrogens with GnRH analogs is relatively contraindicated, as estrogens could counteract the therapeutic effect of GnRH analogs for various hormone-sensitive conditions. In the rare cases that these drugs are used together, close clinical monitoring for the desired clinical and hormonal response is necessary.
    Ethinyl Estradiol; Norethindrone: (Major) Concomitant use of estrogens with GnRH analogs is relatively contraindicated, as estrogens could counteract the therapeutic effect of GnRH analogs for various hormone-sensitive conditions. In the rare cases that these drugs are used together, close clinical monitoring for the desired clinical and hormonal response is necessary.
    Ethinyl Estradiol; Norethindrone; Ferrous fumarate: (Major) Concomitant use of estrogens with GnRH analogs is relatively contraindicated, as estrogens could counteract the therapeutic effect of GnRH analogs for various hormone-sensitive conditions. In the rare cases that these drugs are used together, close clinical monitoring for the desired clinical and hormonal response is necessary.
    Ethinyl Estradiol; Norgestimate: (Major) Concomitant use of estrogens with GnRH analogs is relatively contraindicated, as estrogens could counteract the therapeutic effect of GnRH analogs for various hormone-sensitive conditions. In the rare cases that these drugs are used together, close clinical monitoring for the desired clinical and hormonal response is necessary.
    Ethinyl Estradiol; Norgestrel: (Major) Concomitant use of estrogens with GnRH analogs is relatively contraindicated, as estrogens could counteract the therapeutic effect of GnRH analogs for various hormone-sensitive conditions. In the rare cases that these drugs are used together, close clinical monitoring for the desired clinical and hormonal response is necessary.
    Ezogabine: (Major) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with leuprolide include ezogabine.
    Fingolimod: (Major) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with leuprolide include fingolimod.
    Flecainide: (Major) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with leuprolide include flecainide.
    Fluconazole: (Major) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with leuprolide include fluconazole.
    Fluoxetine: (Major) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with leuprolide include fluoxetine.
    Fluoxetine; Olanzapine: (Major) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with leuprolide include fluoxetine. (Moderate) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with leuprolide include olanzapine.
    Fluoxymesterone: (Major) Leuprolide inhibits steroidogenesis. While no drug interactions have been reported with leuprolide, therapy with androgens would be relatively contraindicated and would counteract the therapeutic effect of leuprolide.
    Fluphenazine: (Minor) Androgen-deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with other medications that prolong the QT interval, such as the phenothiazines. Phenothiazines have been associated with a risk of QT prolongation and/or torsade de pointes (TdP). This risk is generally higher at elevated drugs concentrations of phenothiazines. Agents that prolong the QT interval could lead to torsade de pointes when combined with a phenothiazine, and therefore are generally not recommended for combined use; if they must be used, use with caution and with close monitoring. Also, drugs that cause hyperprolactinemia, such as antipsychotics, should be used with caution with gonadotropin releasing hormone (GnRH) analogs (e.g., leuprolide, others) since hyperprolactinemia downregulates the number of pituitary GnRH receptors.
    Fluticasone; Salmeterol: (Moderate) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with leuprolide include beta-agonists.
    Fluticasone; Umeclidinium; Vilanterol: (Moderate) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with leuprolide include beta-agonists.
    Fluticasone; Vilanterol: (Moderate) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with leuprolide include beta-agonists.
    Fluvoxamine: (Moderate) There may be an increased risk for QT prolongation and torsade de pointes (TdP) during concurrent use of fluvoxamine and leuprolide. Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Cases of QT prolongation and TdP have been reported during postmarketing use of fluvoxamine.
    Formoterol: (Moderate) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with leuprolide include beta-agonists.
    Formoterol; Mometasone: (Moderate) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with leuprolide include beta-agonists.
    Foscarnet: (Major) When possible, avoid concurrent use of foscarnet with other drugs known to prolong the QT interval, such as leuprolide. Foscarnet has been associated with postmarketing reports of both QT prolongation and torsade de pointes (TdP). Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. If these drugs are administered together, obtain an electrocardiogram and electrolyte concentrations before and periodically during treatment.
    Gemifloxacin: (Major) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with leuprolide include gemifloxacin.
    Gemtuzumab Ozogamicin: (Moderate) Use gemtuzumab ozogamicin and leuprolide 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. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. Androgen deprivation therapy (e.g., leuprolide) also prolongs the QT interval.
    Glycopyrrolate; Formoterol: (Moderate) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with leuprolide include beta-agonists.
    Goserelin: (Moderate) Androgen deprivation therapy (e.g., goserelin) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with goserelin include leuprolide.
    Granisetron: (Major) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with leuprolide include granisetron.
    Halofantrine: (Severe) Halofantrine is considered to have a well-established risk for QT prolongation and torsades de pointes (TdP). Halofantrine should be avoided in patients receiving drugs which may induce QT prolongation. Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Because of the potential for TdP, use of halofantrine with leuprolide is contraindicated.
    Halogenated Anesthetics: (Major) Halogenated anesthetics are associated with a risk for QT prolongation and potential cardiac arrhythmias. Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Halogenated anesthetics should be used cautiously and with close monitoring in patients receiving leuprolide.
    Haloperidol: (Major) When possible, avoid use of other drugs that may prolong the QT interval with haloperidol, due to additive risk factors. When use is necessary, close clinical monitoring may be needed. 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. Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval. Additionally, hjyperprolactinemia, which may be caused by antipsychotics, down-regulates the number of pituitary GnRH receptors and may interfere with the response to leuprolide therapy.
    Halothane: (Major) Halogenated anesthetics are associated with a risk for QT prolongation and potential cardiac arrhythmias. Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Halogenated anesthetics should be used cautiously and with close monitoring in patients receiving leuprolide.
    Hydrochlorothiazide, HCTZ; Methyldopa: (Minor) Drugs that cause hyperprolactinemia, such as methyldopa, should generally not be administered concomitantly with GnRH analogs since hyperprolactinemia downregulates the number of pituitary GnRH receptors. Monitor the patient for the proper clinical response to GnRH therapy.
    Hydroxychloroquine: (Major) Avoid coadministration of hydroxychloroquine and leuprolide. Hydroxychloroquine increases the QT interval and should not be administered with other drugs known to prolong the QT interval. Ventricular arrhythmias and torsade de pointes have been reported with the use of hydroxychloroquine. Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval.
    Hydroxyzine: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include leuprolide.
    Ibutilide: (Major) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with leuprolide include ibutilide.
    Idarubicin: (Moderate) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Leuprolide should be used with caution with cardiotoxic drugs. Acute cardiotoxicity can occur during administration of daunorubicin, doxorubicin, epirubicin, or idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Iloperidone: (Major) Iloperidone has been associated with QT prolongation; however, torsade de pointes (TdP) has not been reported. Since iloperidone may prolong the QT interval, it should be avoided in combination with other agents also known to have this effect. Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Additionally, antipsychotic-induced hyperprolactinemia results in down-regulatation of the number of pituitary GnRH receptors and may interfere with the response to leuprolide therapy.
    Imipramine: (Minor) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with leuprolide include tricyclic antidepressants. Tricyclic antidepressants (TCAs) share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations).
    Indacaterol: (Moderate) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with leuprolide include beta-agonists.
    Indacaterol; Glycopyrrolate: (Moderate) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with leuprolide include beta-agonists.
    Inotuzumab Ozogamicin: (Major) Avoid coadministration of inotuzumab ozogamicin with leuprolide 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. Inotuzumab has been associated with QT interval prolongation. Androgen deprivation therapy (e.g., leuprolide) also prolongs the QT interval.
    Isoflurane: (Major) Halogenated anesthetics are associated with a risk for QT prolongation and potential cardiac arrhythmias. Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Halogenated anesthetics should be used cautiously and with close monitoring in patients receiving leuprolide.
    Itraconazole: (Major) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with leuprolide include itraconazole.
    Ketoconazole: (Major) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with leuprolide include ketoconazole.
    Lapatinib: (Major) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with leuprolide include lapatinib.
    Lenvatinib: (Major) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with leuprolide include lenvatinib. QT prolongation was reported in patients with radioactive iodine-refractory differentiated thyroid cancer (RAI-refractory DTC) in a double-blind, randomized, placebo-controlled clinical trial after receiving lenvatinib daily at the recommended dose; the QT/QTc interval was not prolonged, however, after a single 32 mg dose (1.3 times the recommended daily dose) in healthy subjects.
    Levalbuterol: (Minor) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with leuprolide include beta-agonists.
    Levofloxacin: (Major) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with leuprolide include levofloxacin.
    Levomethadyl: (Severe) Levomethadyl is associated with an established risk of QT prolongation and/or torsades de pointes (TdP), particularly at high drug concentrations. Levomethadyl is contraindicated in combination with other agents that may prolong the QT interval. Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Because of the potential for TdP, use of . levomethady with leuprolide is contraindicated.
    Lithium: (Moderate) Lithium should be used cautiously with leuprolide. Lithium has been associated with QT prolongation. Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval.
    Long-acting beta-agonists: (Moderate) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with leuprolide include beta-agonists.
    Loperamide: (Moderate) Loperamide should be used cautiously and with close monitoring with leuprolide. At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, torsade de pointes (TdP), and cardiac arrest. Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of loperamide.
    Loperamide; Simethicone: (Moderate) Loperamide should be used cautiously and with close monitoring with leuprolide. At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, torsade de pointes (TdP), and cardiac arrest. Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of loperamide.
    Lopinavir; Ritonavir: (Major) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with leuprolide include ritonavir.
    Loxapine: (Moderate) Antipsychotic induced hyperprolactinemia results in down-regulatation of the number of pituitary GnRH receptors and may interfere with the response to leuprolide therapy.
    Maprotiline: (Moderate) 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 torsade de pointes (TdP) 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. Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval.
    Mefloquine: (Major) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with leuprolide include mefloquine.
    Meperidine; Promethazine: (Moderate) Androgen-deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with other medications that prolong the QT interval, such as the phenothiazines. Promethazine (a phenothiazine antiemetic and antihistamine) carries a possible risk of QT prolongation. Drugs with a possible risk for QT prolongation and TdP should be used cautiously together.
    Mesoridazine: (Severe) Mesoridazine carries a known risk for QT prolongation and torsade de pointes (TdP), and is contraindicated for use with other medications that may prolong the QT interval. Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Additionally, hjyperprolactinemia, which may be caused by antipsychotics, down-regulates the number of pituitary GnRH receptors and may interfere with the response to leuprolide therapy.
    Mestranol; Norethindrone: (Major) Concomitant use of estrogens with GnRH analogs is relatively contraindicated, as estrogens could counteract the therapeutic effect of GnRH analogs for various hormone-sensitive conditions. In the rare cases that these drugs are used together, close clinical monitoring for the desired clinical and hormonal response is necessary.
    Metaproterenol: (Minor) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with leuprolide include beta-agonists.
    Methadone: (Major) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with leuprolide include methadone.
    Methyldopa: (Minor) Drugs that cause hyperprolactinemia, such as methyldopa, should generally not be administered concomitantly with GnRH analogs since hyperprolactinemia downregulates the number of pituitary GnRH receptors. Monitor the patient for the proper clinical response to GnRH therapy.
    Methyltestosterone: (Major) Leuprolide inhibits steroidogenesis. While no drug interactions have been reported with leuprolide, therapy with androgens would be relatively contraindicated and would counteract the therapeutic effect of leuprolide.
    Metoclopramide: (Minor) Drugs that cause hyperprolactinemia, such as metoclopramide, should generally not be administered concomitantly with GnRH analogs since hyperprolactinemia downregulates the number of pituitary GnRH receptors. Monitor the patient for the proper clinical response to GnRH therapy.
    Midostaurin: (Major) The concomitant use of midostaurin and leuprolide may lead to additive QT interval prolongation. If these drugs are used together, consider electrocardiogram monitoring. In clinical trials, QT prolongation has been reported in patients who received midostaurin as single-agent therapy or in combination with cytarabine and daunorubicin. Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval.
    Mifepristone, RU-486: (Moderate) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with leuprolide include mifepristone, RU-486.
    Mirtazapine: (Moderate) There may be an increased risk for QT prolongation and torsade de pointes (TdP) during concurrent use of mirtazapine and leuprolide. Coadminister with caution. Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. 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.
    Molindone: (Moderate) Antipsychotics may cause hyperprolactinemia should not be administered concomitantly with leuprolide since hyperprolactinemia down-regulates the number of pituitary GnRH receptors.
    Moxifloxacin: (Major) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with leuprolide include moxifloxacin.
    Nandrolone Decanoate: (Major) Leuprolide inhibits steroidogenesis. While no drug interactions have been reported with leuprolide, therapy with androgens would be relatively contraindicated and would counteract the therapeutic effect of leuprolide.
    Nilotinib: (Major) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with leuprolide include nilotinib.
    Norfloxacin: (Moderate) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with leuprolide include norfloxacin.
    Nortriptyline: (Minor) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with leuprolide include tricyclic antidepressants. Tricyclic antidepressants (TCAs) share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations).
    Octreotide: (Moderate) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with leuprolide include octreotide.
    Olanzapine: (Moderate) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with leuprolide include olanzapine.
    Olodaterol: (Moderate) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with leuprolide include beta-agonists.
    Ombitasvir; Paritaprevir; Ritonavir: (Major) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with leuprolide include ritonavir.
    Ondansetron: (Major) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with leuprolide include ondansetron.
    Osimertinib: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of leuprolide with osimertinib is necessary; an interruption of osimertinib therapy and dose reduction may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Androgen deprivation therapy (e.g., leuprolide) also prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval.
    Oxaliplatin: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of leuprolide with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have been reported with oxaliplatin use in postmarketing experience. Androgen deprivation therapy (e.g., leuprolide) also prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval.
    Oxandrolone: (Major) Leuprolide inhibits steroidogenesis. While no drug interactions have been reported with leuprolide, therapy with androgens would be relatively contraindicated and would counteract the therapeutic effect of leuprolide.
    Oxymetholone: (Major) Leuprolide inhibits steroidogenesis. While no drug interactions have been reported with leuprolide, therapy with androgens would be relatively contraindicated and would counteract the therapeutic effect of leuprolide.
    Paliperidone: (Major) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with leuprolide include paliperidone.
    Panobinostat: (Moderate) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with leuprolide include panobinostat. The co-administration of panobinostat with leuprolide is not recommended; QT prolongation has been reported with both agents.
    Pasireotide: (Major) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with leuprolide include pasireotide.
    Pazopanib: (Major) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with leuprolide include pazopanib.
    Pentamidine: (Major) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with leuprolide include pentamidine.
    Perphenazine: (Minor) Androgen-deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with other medications that prolong the QT interval, such as the phenothiazines. Phenothiazines have been associated with a risk of QT prolongation and/or torsade de pointes (TdP). This risk is generally higher at elevated drugs concentrations of phenothiazines. Agents that prolong the QT interval could lead to torsade de pointes when combined with a phenothiazine, and therefore are generally not recommended for combined use; if they must be used, use with caution and with close monitoring. Also, drugs that cause hyperprolactinemia, such as antipsychotics, should be used with caution with gonadotropin releasing hormone (GnRH) analogs (e.g., leuprolide, others) since hyperprolactinemia downregulates the number of pituitary GnRH receptors.
    Perphenazine; Amitriptyline: (Minor) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with leuprolide include tricyclic antidepressants. Tricyclic antidepressants (TCAs) share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). (Minor) Androgen-deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with other medications that prolong the QT interval, such as the phenothiazines. Phenothiazines have been associated with a risk of QT prolongation and/or torsade de pointes (TdP). This risk is generally higher at elevated drugs concentrations of phenothiazines. Agents that prolong the QT interval could lead to torsade de pointes when combined with a phenothiazine, and therefore are generally not recommended for combined use; if they must be used, use with caution and with close monitoring. Also, drugs that cause hyperprolactinemia, such as antipsychotics, should be used with caution with gonadotropin releasing hormone (GnRH) analogs (e.g., leuprolide, others) since hyperprolactinemia downregulates the number of pituitary GnRH receptors.
    Phenylephrine; Promethazine: (Moderate) Androgen-deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with other medications that prolong the QT interval, such as the phenothiazines. Promethazine (a phenothiazine antiemetic and antihistamine) carries a possible risk of QT prolongation. Drugs with a possible risk for QT prolongation and TdP should be used cautiously together.
    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 leuprolide. Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval.
    Pimozide: (Severe) Pimozide carries a known risk for QT prolongation and torsade de pointes (TdP), and is contraindicated for use with other medications that may prolong the QT interval. Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Additionally, hjyperprolactinemia, which may be caused by antipsychotics, down-regulates the number of pituitary GnRH receptors and may interfere with the response to leuprolide therapy.
    Pirbuterol: (Minor) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with leuprolide include beta-agonists.
    Posaconazole: (Major) Posaconazole has been associated with prolongation of the QT interval as well as rare cases of torsade de pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with posaconazole include leuprolide. Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval.
    Prasterone, Dehydroepiandrosterone, DHEA (Dietary Supplements): (Major) Leuprolide inhibits steroidogenesis. While no drug interactions have been reported with leuprolide, therapy with androgens would be relatively contraindicated and would counteract the therapeutic effect of leuprolide.
    Prasterone, Dehydroepiandrosterone, DHEA (FDA-approved): (Major) Leuprolide inhibits steroidogenesis. While no drug interactions have been reported with leuprolide, therapy with androgens would be relatively contraindicated and would counteract the therapeutic effect of leuprolide.
    Primaquine: (Major) 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 leuprolide.
    Procainamide: (Major) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with leuprolide include procainamide.
    Prochlorperazine: (Minor) Androgen-deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with other medications that prolong the QT interval, such as the phenothiazines. Phenothiazines have been associated with a risk of QT prolongation and/or torsade de pointes (TdP). This risk is generally higher at elevated drugs concentrations of phenothiazines. Agents that prolong the QT interval could lead to torsade de pointes when combined with a phenothiazine, and therefore are generally not recommended for combined use; if they must be used, use with caution and with close monitoring. Also, drugs that cause hyperprolactinemia, such as antipsychotics, should be used with caution with gonadotropin releasing hormone (GnRH) analogs (e.g., leuprolide, others) since hyperprolactinemia downregulates the number of pituitary GnRH receptors.
    Promethazine: (Moderate) Androgen-deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with other medications that prolong the QT interval, such as the phenothiazines. Promethazine (a phenothiazine antiemetic and antihistamine) carries a possible risk of QT prolongation. Drugs with a possible risk for QT prolongation and TdP should be used cautiously together.
    Propafenone: (Major) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with leuprolide include propafenone.
    Protriptyline: (Minor) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with leuprolide include tricyclic antidepressants. Tricyclic antidepressants (TCAs) share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations).
    Quetiapine: (Moderate) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Quetiapine is associated with a possible risk for QT prolongation and TdP and should be used cautiously and with close monitoring with leuprolide. Additionally, some antipsychotics may induce hyperprolactinemia, resulting in down-regulation of the number of pituitary GnRH receptors and may interfere with the response to leuprolide therapy.
    Quinidine: (Major) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Quinidine is associated with QT prolongation and torsades de pointes (TdP).
    Ranolazine: (Major) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with leuprolide include ranolazine.
    Regadenoson: (Moderate) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with leuprolide include regadenoson.
    Reserpine: (Minor) Drugs that cause hyperprolactinemia, such as reserpine, should not be administered concomitantly with GnRH analogs since hyperprolactinemia downregulates the number of pituitary GnRH receptors.
    Ribociclib: (Major) Avoid coadministration of ribociclib with leuprolide due to an increased risk for QT prolongation. Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval.
    Ribociclib; Letrozole: (Major) Avoid coadministration of ribociclib with leuprolide due to an increased risk for QT prolongation. Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval.
    Rilpivirine: (Major) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with leuprolide include rilpivirine.
    Risperidone: (Major) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with leuprolide include risperidone.
    Ritonavir: (Major) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with leuprolide include ritonavir.
    Romidepsin: (Major) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with leuprolide include romidepsin.
    Salmeterol: (Moderate) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with leuprolide include beta-agonists.
    Saquinavir: (Major) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with leuprolide include saquinavir.
    Sertraline: (Moderate) There have been post-marketing reports of QT prolongation and torsade de pointes (TdP) during treatment with sertraline; therefore, caution is advisable when using sertraline in patients with risk factors for QT prolongation, including concurrent use of other drugs that prolong the QTc interval. Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval
    Sevoflurane: (Major) Halogenated anesthetics are associated with a risk for QT prolongation and potential cardiac arrhythmias. Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Halogenated anesthetics should be used cautiously and with close monitoring in patients receiving leuprolide.
    Short-acting beta-agonists: (Minor) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with leuprolide include beta-agonists.
    Solifenacin: (Moderate) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with leuprolide include solifenacin.
    Sorafenib: (Major) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with leuprolide include sorafenib.
    Sotalol: (Major) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with leuprolide include sotalol.
    Sparfloxacin: (Severe) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Because of the potential for TdP, use of sparfloxacin with leuprolide is contraindicated.
    Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole: (Moderate) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with leuprolide include sulfamethoxazole; trimethoprim. (Moderate) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with leuprolide include trimethoprim.
    Sunitinib: (Major) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with leuprolide include sunitinib.
    Tacrolimus: (Major) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with leuprolide include tacrolimus.
    Tamoxifen: (Moderate) Caution is advised with the concomitant use of tamoxifen and leuprolide due to an increased risk of QT prolongation. Tamoxifen has 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. Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval.
    Telavancin: (Major) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with leuprolide include telavancin.
    Telithromycin: (Major) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with leuprolide include telithromycin.
    Terbutaline: (Minor) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with leuprolide include beta-agonists.
    Terfenadine: (Severe) Androgen deprivation therapy (e.g., leuprolide) may prolong the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Because of the potential for QT prolongation and torsade de pointes (TdP), use of terfenadine, a drug with an established risk for TdP, with leuprolide is contraindicated.
    Testolactone: (Major) Leuprolide inhibits steroidogenesis. While no drug interactions have been reported with leuprolide, therapy with androgens would be relatively contraindicated and would counteract the therapeutic effect of leuprolide.
    Testosterone: (Major) Leuprolide inhibits steroidogenesis. While no drug interactions have been reported with leuprolide, therapy with androgens would be relatively contraindicated and would counteract the therapeutic effect of leuprolide.
    Tetrabenazine: (Major) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval, such as tetrabenazine. In addition, drugs that cause hyperprolactinemia, such as tetrabenazine, should not be administered concomitantly with gonadotropin-releasing hormone (GnRH) analogs (leuprolide) since hyperprolactinemia down regulates the number of pituitary GnRH receptors.
    Thioridazine: (Severe) Thioridazine carries a known risk for QT prolongation and torsade de pointes (TdP), and is contraindicated for use with other medications that may prolong the QT interval. Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Because of the potential for TdP, use of thioridazine with leuprolide is contraindicated. Additionally, antipsychotic-induced hyperprolactinemia results in down-regulatation of the number of pituitary GnRH receptors and may interfere with the response to leuprolide therapy.
    Thiothixene: (Moderate) Antipsychotic induced hyperprolactinemia results in down-regulatation of the number of pituitary GnRH receptors and may interfere with the response to leuprolide therapy.
    Tiotropium; Olodaterol: (Moderate) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with leuprolide include beta-agonists.
    Tizanidine: (Moderate) Tizanidine should be used cautiously and with close monitoring with leuprolide. Tizanidine administration may result in QT prolongation. Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval.
    Tolterodine: (Moderate) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with leuprolide include tolterodine.
    Toremifene: (Major) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with leuprolide include toremifene.
    Trazodone: (Major) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with leuprolide include trazodone.
    Tricyclic antidepressants: (Minor) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with leuprolide include tricyclic antidepressants. Tricyclic antidepressants (TCAs) share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations).
    Trifluoperazine: (Minor) Androgen-deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with other medications that prolong the QT interval, such as the phenothiazines. Phenothiazines have been associated with a risk of QT prolongation and/or torsade de pointes (TdP). This risk is generally higher at elevated drugs concentrations of phenothiazines. Agents that prolong the QT interval could lead to torsade de pointes when combined with a phenothiazine, and therefore are generally not recommended for combined use; if they must be used, use with caution and with close monitoring. Also, drugs that cause hyperprolactinemia, such as antipsychotics, should be used with caution with gonadotropin releasing hormone (GnRH) analogs (e.g., leuprolide) since hyperprolactinemia downregulates the number of pituitary GnRH receptors.
    Trimethoprim: (Moderate) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with leuprolide include trimethoprim.
    Trimipramine: (Minor) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with leuprolide include tricyclic antidepressants. Tricyclic antidepressants (TCAs) share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations).
    Umeclidinium; Vilanterol: (Moderate) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with leuprolide include beta-agonists.
    Vandetanib: (Major) The manufacturer of vandetanib advises against coadministration with other drugs that prolong the QT interval due to an increased risk of QT prolongation and torsade de pointes (TdP).Vandetanib can prolong the QT interval in a concentration-dependent manner. TdP and sudden death have been reported in patients receiving vandetanib. Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval. If a drug that can prolong the QT interval, such as leuprolide, is given to a patient already taking vandetanib and no alternative therapy exists, perform more frequent monitoring of the QT interval. Monitor an ECG before and during use. If QTcF is greater than 500 msec, interrupt vandetanib dosing until the QTcF is less than 450 msec; then, vandetanib may be resumed at a reduced dose.
    Vardenafil: (Major) Therapeutic (10 mg) and supratherapeutic (80 mg) doses of vardenafil produce an increase in QTc interval (e.g., 4 to 6 msec calculated by individual QT correction). When vardenafil (10 mg) was given with another drug that is known to cause QT prolongation, an additive effect on the QT interval was observed. The effect of vardenafil on the QT interval should be considered when prescribing the drug. Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Use leuprolide and vardenafil together with caution and with close clinical monitoring if use together is not avoidable.
    Vemurafenib: (Major) Vemurafenib has been associated with QT prolongation. If vemurafenib and another drug associated with a possible risk for QT prolongation and torsade de pointes (TdP) must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation. Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval.
    Venlafaxine: (Moderate) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with leuprolide include venlafaxine.
    Voriconazole: (Major) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with leuprolide include voriconazole. Voriconazole has been associated with QT prolongation and rare cases of torsades de pointes.
    Vorinostat: (Moderate) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with leuprolide include vorinostat.
    Ziprasidone: (Severe) Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Ziprasidone is contraindicated with any drug that lists QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Because of the potential for TdP, use of ziprasidone with leuprolide is contraindicated. Additionally, antipsychotic-induced hyperprolactinemia results in down-regulatation of the number of pituitary GnRH receptors and may interfere with the response to leuprolide therapy.

    PREGNANCY AND LACTATION

    Pregnancy

    Because the consequences to the nursing infant are not known, breast-feeding should be avoided during treatment with leuprolide. The Viadur implant and Eligard brands of leuprolide are contraindicated in females due to due to a lack of indication for use and limited experience, thus these products would not be given to the lactating female.

    MECHANISM OF ACTION

    Leuprolide provides a medical castration for the patient and deprives hormonally-dependent tumors of testosterone or estrogen. During short-term or intermittent therapy, leuprolide has the same stimulatory action as GnRH, but long-term therapy suppresses gonadotropin release from the pituitary gland and reduces steroidogenesis in the ovaries and testicles. Normally, GnRH is released in a pulsatile fashion, but the sustained activity of leuprolide leads to downregulation of the receptor and decreased production of follicle-stimulating hormone (FSH) and luteinizing hormone (LH). In the male, this activity stops testosterone production in the testis. In the female, it stops estrogen production in the ovaries. In patients with endometriosis, this reversible hypoestrogenic state produces symptomatic relief of the pain of endometriosis and decreases the number of endometriotic lesions. Initially, there is a surge of FSH and LH, which can cause a flare reaction in prostate or breast carcinoma. Eventually, the flare reaction will diminish. Total castration can be expected in 1—2 weeks.

    PHARMACOKINETICS

    Leuprolide is administered subcutaneously or intramuscularly. Once absorbed, relatively high concentrations of the drug can be found in liver, pineal, kidney, and pituitary tissues. In vitro binding to human protein ranged 43—49%. Like the naturally occurring hormone, leuprolide can be metabolized in the anterior pituitary and hypothalamus. The plasma elimination half-life of leuprolide is estimated to be about 3 hours.

    Intramuscular Route

    Peak levels following an intramuscular injection of leuprolide occur at 4 hours. Studies of the depot intramuscular injection in adults indicate that about 20—25% is absorbed each week into the circulation.

    Subcutaneous Route

    Leuprolide subcutaneous injection is rapidly and completely absorbed with a bioavailability of about 94%.