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  • 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, leuprolide must be given with norethindrone acetate 5 mg/day PO for 6 months; the total duration of therapy with leuprolide plus norethindrone acetate should not exceed 12 months. Assessment of bone density is recommended before retreatment. 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.

    Contraception requirements, females, pregnancy, pregnancy testing

    Although leuprolide has been used as an adjunct in fertility protocols, leuprolide is contraindicated during pregnancy because spontaneous abortion could occur once conception ensues. Leuprolide may cause fetal harm if administered to a pregnant woman; pregnancy must be ruled out before initiating treatment with leuprolide; pregnancy testing is recommended in females of childbearing potential prior to use to establish that the patient is not pregnant. When used at the recommended dose and dosing interval, leuprolide usually inhibits ovulation and stops menstruation; however, contraception is not ensured by taking leuprolide. Therefore, contraception requirements such as non-hormonal methods are required. Advise patients to notify their healthcare provider if they believe they may be pregnant. Discontinue leuprolide if a patient becomes pregnant during treatment and inform the patient of potential risk to the fetus. The higher-dose Lupron Depot products, Viadur implant and Eligard products are contraindicated in females due to limited experience and lack of an indication for use in females.

    Breast-feeding

    Because the consequences on lactation and 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

    epididymitis / Delayed / 0-5.0
    renal tubular obstruction / 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
    erythema multiforme / Delayed / 0-0.1
    anaphylactoid reactions / Rapid / 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
    new primary malignancy / 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
    urinary incontinence / Early / 0-5.0
    bladder spasm / Early / 0-5.0
    dysuria / 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
    hyperuricemia / Delayed / 5.0
    hyperphosphatemia / 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
    nephrolithiasis / 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
    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
    melasma / Delayed / 0-5.0
    alopecia / Delayed / 0-5.0
    skin hyperpigmentation / Delayed / 0-5.0
    xerosis / 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
    seborrhea / Delayed / 3.0-3.0
    rash / Early / 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
    skin hypopigmentation / Delayed / 0-2.0
    purpura / Delayed / 0-2.0
    urticaria / Rapid / 0-0.1
    photosensitivity / Delayed / 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

    Aclidinium; Formoterol: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving long-acting beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. Androgen deprivation therapy may also prolong the QT/QTc interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Albuterol: (Minor) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving short-acting beta-agonists. Androgen deprivation therapy may prolong the QT/QTc interval. Beta-agonists may also be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Albuterol; Ipratropium: (Minor) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving short-acting beta-agonists. Androgen deprivation therapy may prolong the QT/QTc interval. Beta-agonists may also be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Alfuzosin: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving alfuzosin. Androgen deprivation therapy may prolong the QT/QTc interval. Based on electrophysiology studies performed by the manufacturer, alfuzosin may also prolong the QT interval in a dose-dependent manner.
    Amiodarone: (Major) Avoid coadministration of amiodarone with triptorelin if possible due to the risk of QT prolongation. Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks in patients receiving amiodarone. Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsade de pointes (TdP), although the frequency of TdP is less with amiodarone than with other Class III agents. Androgen deprivation therapy also prolongs 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.
    Amitriptyline: (Minor) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving tricyclic antidepressants (TCAs). Tricyclic antidepressants 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). Androgen deprivation therapy may also prolong the QT/QTc interval.
    Amitriptyline; Chlordiazepoxide: (Minor) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving tricyclic antidepressants (TCAs). Tricyclic antidepressants 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). Androgen deprivation therapy may also prolong the QT/QTc interval.
    Amoxapine: (Major) Avoid coadministration of leuprolide with amoxapine due to the risk of reduced efficacy of leuprolide. Amoxapine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog.
    Amoxicillin; Clarithromycin; Lansoprazole: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving clarithromycin. Clarithromycin is associated with an established risk for QT prolongation and torsade de pointes (TdP). Androgen deprivation therapy may also prolong the QT/QTc interval.
    Amoxicillin; Clarithromycin; Omeprazole: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving clarithromycin. Clarithromycin is associated with an established risk for QT prolongation and torsade de pointes (TdP). Androgen deprivation therapy may also prolong the QT/QTc interval.
    Anagrelide: (Major) Do not use anagrelide with other drugs that prolong the QT interval such as leuprolide. Torsade de pointes (TdP) and ventricular tachycardia have been reported with anagrelide; in addition, dose-related increases in mean QTc and heart rate were observed in healthy subjects. 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.
    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.
    Apomorphine: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving apomorphine. Androgen deprivation therapy may prolong the QT/QTc interval. Limited data indicate that QT prolongation is also possible with apomorphine administration; the change in QTc interval is not significant in most patients receiving dosages within the manufacturer's guidelines.
    Arformoterol: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving long-acting beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. Androgen deprivation therapy may also prolong the QT/QTc interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Aripiprazole: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving aripiprazole. Androgen deprivation therapy may prolong the QT/QTc interval. Prolongation of the QT interval has also occurred during therapeutic use of aripiprazole and following overdose.
    Arsenic Trioxide: (Major) Avoid concomitant use of arsenic trioxide with leuprolide; discontinue or select an alternative drug that does not prolong the QT interval prior to starting arsenic trioxide therapy. If concomitant drug use is unavoidable, frequently monitor electrocardiograms. Torsade de pointes (TdP), QT interval prolongation, and complete atrioventricular block have been reported with arsenic trioxide use. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
    Artemether; Lumefantrine: (Major) Avoid coadministration of artemether with leuprolide if possible due to the risk of QT prolongation. Consider ECG monitoring if leuprolide must be used with or after artemether; lumefantrine treatment. Artemether; lumefantrine is associated with prolongation of the QT interval. Androgen deprivation therapy (i.e., leuprolide) may prolong the QT/QTc interval. (Major) Avoid coadministration of lumefantrine with leuprolide if possible due to the risk of QT prolongation. Consider ECG monitoring if leuprolide must be used with or after artemether; lumefantrine treatment. Artemether; lumefantrine is associated with prolongation of the QT interval. Androgen deprivation therapy (i.e., leuprolide) may prolong the QT/QTc interval.
    Asenapine: (Major) Avoid coadministration of leuprolide with asenapine due to the risk of reduced efficacy of leuprolide as well as the risk of QT prolongation. Asenapine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog. Additionally, asenapine has been associated with QT prolongation. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
    Atomoxetine: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving atomoxetine as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy may prolong the QT/QTc interval. Prolongation of the QT interval has also occurred during therapeutic use of atomoxetine and following overdose.
    Azithromycin: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving azithromycin. Androgen deprivation therapy may prolong the QT/QTc interval. Prolongation of the QT interval and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance.
    Bedaquiline: (Major) Frequently monitor ECGs for QT prolongation if coadministration of bedaquiline with leuprolide is necessary. Bedaquiline has been reported to prolong the QT interval; coadministration with other QT prolonging drugs may result in additive or synergistic prolongation of the QT interval. Androgen deprivation therapy may also prolong the QT/QTc interval.
    Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving metronidazole. Potential QT prolongation has been reported in limited case reports with metronidazole. Androgen deprivation therapy may also prolong the QT/QTc interval.
    Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving metronidazole. Potential QT prolongation has been reported in limited case reports with metronidazole. Androgen deprivation therapy may also prolong the QT/QTc interval.
    Brexpiprazole: (Major) Avoid coadministration of leuprolide with brexpiprazole due to the risk of reduced efficacy of leuprolide. Brexpiprazole can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog.
    Budesonide; Formoterol: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving long-acting beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. Androgen deprivation therapy may also prolong the QT/QTc interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Buprenorphine: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving buprenorphine. Buprenorphine has 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. Androgen deprivation therapy may also prolong the QT/QTc interval.
    Buprenorphine; Naloxone: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving buprenorphine. Buprenorphine has 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. Androgen deprivation therapy may also prolong the QT/QTc interval.
    Cariprazine: (Major) Avoid coadministration of leuprolide with cariprazine due to the risk of reduced efficacy of leuprolide. Cariprazine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog.
    Ceritinib: (Major) Avoid coadministration of ceritinib with leuprolide if possible due to the risk of QT prolongation. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent QT prolongation. Androgen deprivation therapy (i.e., leuprolide) may prolong the QT/QTc interval.
    Chloroquine: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving chloroquine. Chloroquine is associated with an increased risk of QT prolongation and torsade de pointes (TdP); fatalities have been reported. The risk of QT prolongation is increased with higher chloroquine doses. Androgen deprivation therapy may also prolong the QT/QTc interval.
    Chlorpromazine: (Major) Avoid coadministration of leuprolide with chlorpromazine due to the risk of reduced efficacy of leuprolide; QT prolongation may also occur. Chlorpromazine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog. Additionally, chlorpromazine, a phenothiazine, is associated with an established risk of QT prolongation and torsade de pointes (TdP). Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
    Ciprofloxacin: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving ciprofloxacin. Androgen deprivation therapy may prolong the QT/QTc interval. Rare cases of QT prolongation and torsade de pointes (TdP) have also been reported with ciprofloxacin during postmarketing surveillance.
    Cisapride: (Severe) Because of the potential for QT prolongation and torsade de pointes (TdP), the use of leuprolide with cisapride is contraindicated. Prolongation of the QT interval and ventricular arrhythmias, including TdP and death, have been reported with cisapride. 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.
    Citalopram: (Major) Coadministration of citalopram with leuprolide is not recommended due to the risk of QT prolongation. If concurrent therapy is considered essential, ECG monitoring is recommended. Citalopram causes dose-dependent QT interval prolongation. Androgen deprivation therapy (i.e., leuprolide) may prolong the QT/QTc interval.
    Clarithromycin: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving clarithromycin. Clarithromycin is associated with an established risk for QT prolongation and torsade de pointes (TdP). Androgen deprivation therapy may also prolong the QT/QTc interval.
    Clofazimine: (Major) Monitor ECGs for QT prolongation when clofazimine is administered with leuprolide. Prolongation of the QT interval and torsade de pointes (TdP) have been reported in patients receiving clofazimine in combination with QT prolonging medications. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
    Clomipramine: (Minor) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving tricyclic antidepressants (TCAs). Tricyclic antidepressants 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). Androgen deprivation therapy may also prolong the QT/QTc interval.
    Clozapine: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving clozapine as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy may prolong the QT/QTc interval. Treatment with clozapine has been associated with QT prolongation, torsade de pointes (TdP), cardiac arrest, and sudden death. Androgen deprivation therapy may prolong the QT/QTc interval.
    Codeine; Phenylephrine; Promethazine: (Major) Avoid coadministration of leuprolide with promethazine due to the risk of reduced efficacy of leuprolide; QT prolongation may also occur. Promethazine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog. Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
    Codeine; Promethazine: (Major) Avoid coadministration of leuprolide with promethazine due to the risk of reduced efficacy of leuprolide; QT prolongation may also occur. Promethazine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog. Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
    Crizotinib: (Major) Avoid coadministration of crizotinib with leuprolide due to the risk of QT prolongation. If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary for crizotinib if QT prolongation occurs. Crizotinib has been associated with concentration-dependent QT prolongation. 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.
    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.
    Dasatinib: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving dasatinib as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy may prolong the QT/QTc interval. In vitro studies have shown that dasatinib also has the potential to prolong the QT interval.
    Desflurane: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving halogenated anesthetics. Androgen deprivation therapy may prolong the QT/QTc interval. Halogenated anesthetics can also prolong the QT interval.
    Desipramine: (Minor) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving tricyclic antidepressants (TCAs). Tricyclic antidepressants 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). Androgen deprivation therapy may also prolong the QT/QTc interval.
    Deutetrabenazine: (Major) Avoid coadministration of leuprolide with deutetrabenazine due to the risk of reduced efficacy of leuprolide; QT prolongation may also occur. Deutetrabenazine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog. Clinically relevant QTc prolongation may occur with deutetrabenazine; the manufacturer provides recommendations for ECG monitoring if deutetrabenazine is coadministered with other QT prolonging medications at doses greater than 24 mg/day. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
    Dextromethorphan; Promethazine: (Major) Avoid coadministration of leuprolide with promethazine due to the risk of reduced efficacy of leuprolide; QT prolongation may also occur. Promethazine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog. Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
    Dextromethorphan; Quinidine: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving quinidine. Quinidine administration is associated with QT prolongation and torsade de pointes (TdP). Androgen deprivation therapy may also prolong the QT/QTc interval.
    Disopyramide: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving disopyramide. Androgen deprivation therapy may prolong the QT/QTc interval. Disopyramide administration is also associated with QT prolongation and torsade de pointes (TdP).
    Dofetilide: (Major) Coadministration of dofetilide and leuprolide is not recommended as concurrent use may increase the risk of QT prolongation. Dofetilide, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Androgen deprivation therapy (i.e., leuprolide) may prolong the QT/QTc interval.
    Dolasetron: (Moderate) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving dolasetron as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy (i.e., leuprolide) may prolong the QT/QTc interval. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
    Dolutegravir; Rilpivirine: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving rilpivirine as concurrent use may increase the risk of QT prolongation. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Androgen deprivation therapy may also prolong the QT/QTc interval.
    Donepezil: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving donepezil. Androgen deprivation therapy may prolong the QT/QTc interval. Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy.
    Donepezil; Memantine: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving donepezil. Androgen deprivation therapy may prolong the QT/QTc interval. Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy.
    Doxepin: (Minor) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving tricyclic antidepressants (TCAs). Tricyclic antidepressants 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). Androgen deprivation therapy may also prolong the QT/QTc interval.
    Dronedarone: (Severe) Because of the potential for torsade de pointes (TdP), use of leuprolide with dronedarone is contraindicated. 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 1,600 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. Androgen deprivation therapy (e.g., leuprolide) may also prolong the QT/QTc interval.
    Droperidol: (Major) Droperidol should not be used in combination with any drug known to have potential to prolong the QT interval, such as leuprolide. If coadministration is unavoidable, use extreme caution; initiate droperidol at a low dose and increase the dose as needed to achieve the desired effect. Droperidol administration is associated with an established risk for QT prolongation and torsade de pointes (TdP). Some cases have occurred in patients with no known risk factors for QT prolongation and some cases have been fatal. Androgen deprivation therapy (i.e., leuprolide) may prolong the QT/QTc interval.
    Efavirenz: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving efavirenz as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy may prolong the QT/QTc interval. Prolongation of the QTc interval has also been observed with the use of efavirenz.
    Efavirenz; Emtricitabine; Tenofovir: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving efavirenz as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy may prolong the QT/QTc interval. Prolongation of the QTc interval has also been observed with the use of efavirenz.
    Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving efavirenz as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy may prolong the QT/QTc interval. Prolongation of the QTc interval has also been observed with the use of efavirenz.
    Eliglustat: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving eliglustat. Androgen deprivation therapy may prolong the QT/QTc interval. Eliglustat is also predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations.
    Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving rilpivirine as concurrent use may increase the risk of QT prolongation. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Androgen deprivation therapy may also prolong the QT/QTc interval.
    Emtricitabine; Rilpivirine; Tenofovir disoproxil fumarate: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving rilpivirine as concurrent use may increase the risk of QT prolongation. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Androgen deprivation therapy may also prolong the QT/QTc interval.
    Encorafenib: (Major) Avoid coadministration of encorafenib and leuprolide due to the risk of QT prolongation. If concurrent use cannot be avoided, monitor ECGs for QT prolongation and monitor electrolytes; correct hypokalemia and hypomagnesemia prior to treatment. Encorafenib has been associated with dose-dependent QT prolongation. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
    Enflurane: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving halogenated anesthetics. Androgen deprivation therapy may prolong the QT/QTc interval. Halogenated anesthetics can also prolong the QT interval.
    Entrectinib: (Major) Avoid coadministration of entrectinib with leuprolide due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. Androgen deprivation therapy (i.e., leuprolide) may prolong the QT/QTc interval.
    Eribulin: (Major) Closely monitor ECGs for QT prolongation if coadministration of eribulin with leuprolide is necessary. Eribulin has been associated with QT prolongation. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
    Erythromycin: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving erythromycin. Erythromycin is associated with QT prolongation and torsade de pointes (TdP). Androgen deprivation therapy may also prolong the QT/QTc interval.
    Erythromycin; Sulfisoxazole: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving erythromycin. Erythromycin is associated with QT prolongation and torsade de pointes (TdP). Androgen deprivation therapy may also prolong the QT/QTc interval.
    Escitalopram: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving escitalopram as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy may prolong the QT/QTc interval. Escitalopram has also been associated with a risk of QT prolongation and torsade de pointes (TdP).
    Esterified Estrogens; 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.
    Ezogabine: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving ezogabine. Androgen deprivation therapy may prolong the QT/QTc interval. Ezogabine has also been associated with QT prolongation.
    Fingolimod: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving fingolimod as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy may prolong the QT/QTc interval. Fingolimod initiation results in decreased heart rate and may prolong the QT interval. Fingolimod has not been studied in patients treated with drugs that prolong the QT interval, but drugs that prolong the QT interval have been associated with cases of TdP in patients with bradycardia.
    Flecainide: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving flecainide. Flecainide is a Class IC antiarrhythmic associated with a possible risk for QT prolongation and/or torsade de pointes (TdP); flecainide increases the QT interval, but largely due to prolongation of the QRS interval. Androgen deprivation therapy may also prolong the QT/QTc interval. Although causality for TdP has not been established for flecainide, patients receiving concurrent drugs that have the potential for QT prolongation may have an increased risk of developing proarrhythmias.
    Fluconazole: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving fluconazole as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy may prolong the QT/QTc interval. Fluconazole has also been associated with QT prolongation as well as rare cases of torsade de pointes (TdP).
    Fluoxetine: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks in patients receiving fluoxetine. Coadministration of fluoxetine and leuprolide may increase the risk for QT prolongation and torsade de pointes (TdP). QT prolongation and TdP have been reported in patients treated with fluoxetine. Androgen deprivation therapy may prolong the QT/QTc interval.
    Fluoxetine; Olanzapine: (Major) Avoid coadministration of leuprolide with olanzapine due to the risk of reduced efficacy of leuprolide; QT prolongation may also occur. Olanzapine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval. (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks in patients receiving fluoxetine. Coadministration of fluoxetine and leuprolide may increase the risk for QT prolongation and torsade de pointes (TdP). QT prolongation and TdP have been reported in patients treated with fluoxetine. Androgen deprivation therapy may prolong the QT/QTc interval.
    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: (Major) Avoid coadministration of leuprolide with fluphenazine due to the risk of reduced efficacy of leuprolide; QT prolongation may also occur. Fluphenazine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog. Additionally, androgen deprivation therapy (i.e., leuprolide) may prolong the QT/QTc interval. Fluphenazine is also associated with a possible risk for QT prolongation. Theoretically, fluphenazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation.
    Fluticasone; Salmeterol: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving long-acting beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. Androgen deprivation therapy may also prolong the QT/QTc interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Fluticasone; Umeclidinium; Vilanterol: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving long-acting beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. Androgen deprivation therapy may also prolong the QT/QTc interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Fluticasone; Vilanterol: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving long-acting beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. Androgen deprivation therapy may also prolong the QT/QTc interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Fluvoxamine: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving fluvoxamine. Androgen deprivation therapy may prolong the QT/QTc interval. Prolongation of the QT interval and torsade de pointes (TdP) has also been reported during fluvoxamine post-marketing use.
    Formoterol: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving long-acting beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. Androgen deprivation therapy may also prolong the QT/QTc interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Formoterol; Mometasone: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving long-acting beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. Androgen deprivation therapy may also prolong the QT/QTc interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Foscarnet: (Major) Avoid coadministration of foscarnet with leuprolide due to the risk of QT prolongation. Androgen deprivation therapy (i.e., leuprolide) may prolong the QT/QTc interval. Both QT prolongation and torsade de pointes (TdP) have been reported during postmarketing use of foscarnet.
    Gemifloxacin: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving gemifloxacin as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy may prolong the QT/QTc interval. Gemifloxacin may also prolong the QT interval in some patients. The maximal change in the QTc interval occurs approximately 5 to 10 hours following oral administration of gemifloxacin. The likelihood of QTc prolongation may increase with increasing dose of the drug; therefore, the recommended dose should not be exceeded especially in patients with renal or hepatic impairment where the Cmax and AUC are slightly higher. Androgen deprivation therapy may also prolong the QT/QTc interval.
    Gemtuzumab Ozogamicin: (Moderate) Obtain an ECG and serum electrolytes prior to initiation of concomitant use of gemtuzumab ozogamicin and leuprolide due to the potential for additive QT prolongation and the risk of torsade de pointes (TdP); monitor ECGs and electrolytes as needed during treatment. Androgen deprivation therapy (i.e., leuprolide) may prolong the QT/QTc interval. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin.
    Gilteritinib: (Moderate) Use caution and monitor for additive QT prolongation if concurrent use of gilteritinib and leuprolide is necessary as concurrent use may increase the risk of QT prolongation. Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving other QT prolonging agents. Androgen deprivation therapy (i.e., leuprolide) may prolong the QT/QTc interval. Gilteritinib has also been associated with QT prolongation.
    Glasdegib: (Major) Avoid coadministration of glasdegib with leuprolide due to the potential for additive QT prolongation. If coadministration cannot be avoided, monitor patients for increased risk of QT prolongation with increased frequency of ECG monitoring. Glasdegib therapy may result in QT prolongation and ventricular arrhythmias including ventricular fibrillation and ventricular tachycardia. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
    Glycopyrrolate; Formoterol: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving long-acting beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. Androgen deprivation therapy may also prolong the QT/QTc interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Granisetron: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving granisetron as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy may prolong the QT/QTc interval. Granisetron has also been associated with QT prolongation.
    Halogenated Anesthetics: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving halogenated anesthetics. Androgen deprivation therapy may prolong the QT/QTc interval. Halogenated anesthetics can also prolong the QT interval.
    Haloperidol: (Major) Avoid coadministration of leuprolide with haloperidol due to the risk of reduced efficacy of leuprolide; QT prolongation may also occur. Haloperidol can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog. Additionally, QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment; excessive doses (particularly in the overdose setting) or IV administration may be associated with a higher risk. Androgen deprivation therapy (i.e., leuprolide) may prolong the QT/QTc interval.
    Halothane: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving halogenated anesthetics. Androgen deprivation therapy may prolong the QT/QTc interval. Halogenated anesthetics can also prolong the QT interval.
    Hydrochlorothiazide, HCTZ; Methyldopa: (Major) Avoid coadministration of leuprolide with methyldopa due to the risk of reduced efficacy of leuprolide. Methyldopa can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog.
    Hydroxychloroquine: (Major) Avoid coadministration of hydroxychloroquine and leuprolide due to the risk of QT prolongation. Hydroxychloroquine prolongs the QT interval. Androgen deprivation therapy (e.g., leuprolide) also may prolong the QT/QTc interval.
    Hydroxyzine: (Moderate) Caution is recommended if hydroxyzine is administered with leuprolide due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Androgen deprivation therapy may prolong the QT/QTc interval.
    Ibutilide: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving ibutilide. Ibutilide administration can cause QT prolongation and torsade de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval. Androgen deprivation therapy may also prolong the QT/QTc interval.
    Iloperidone: (Major) Avoid coadministration of leuprolide with iloperidone due to the risk of reduced efficacy of leuprolide; QT prolongation may also occur. Iloperidone can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog. Iloperidone has been associated with QT prolongation. Androgen deprivation therapy (i.e., leuprolide) may prolong the QT/QTc interval.
    Imipramine: (Minor) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving tricyclic antidepressants (TCAs). Tricyclic antidepressants 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). Androgen deprivation therapy may also prolong the QT/QTc interval.
    Indacaterol: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving long-acting beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. Androgen deprivation therapy may also prolong the QT/QTc interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Indacaterol; Glycopyrrolate: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving long-acting beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. Androgen deprivation therapy may also prolong the QT/QTc interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Inotuzumab Ozogamicin: (Major) Avoid coadministration of inotuzumab with leuprolide due to the potential for additive QT prolongation and torsade de pointes (TdP). If coadministration is unavoidable, obtain ECGs prior to the start of treatment and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Androgen deprivation therapy (i.e., leuprolide ) may prolong the QT/QTc interval.
    Isoflurane: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving halogenated anesthetics. Androgen deprivation therapy may prolong the QT/QTc interval. Halogenated anesthetics can also prolong the QT interval.
    Itraconazole: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving itraconazole as concurrent use may increase the risk of QT prolongation. Itraconazole has been associated with prolongation of the QT interval. Androgen deprivation therapy may also prolong the QT/QTc interval.
    Ivosidenib: (Major) Avoid coadministration of ivosidenib with leuprolide if possible due to an increased risk of QT prolongation. If concomitant use is unavoidable, monitor ECGs for QTc prolongation and monitor electrolytes; correct any electrolyte abnormalities as clinically appropriate. An interruption of therapy and dose reduction of ivosidenib may be necessary if QT prolongation occurs. Prolongation of the QTc interval and ventricular arrhythmias have been reported in patients treated with ivosidenib. Androgen deprivation therapy (i.e., leuprolide) also may prolong the QT/QTc interval.
    Ketoconazole: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving ketoconazole as concurrent use may increase the risk of QT prolongation. Ketoconazole has been associated with prolongation of the QT interval. Androgen deprivation therapy may also prolong the QT/QTc interval.
    Lapatinib: (Moderate) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving lapatinib as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy (i.e., leuprolide) may prolong the QT/QTc interval. Lapatinib has been associated with concentration-dependent QT prolongation; ventricular arrhythmias and torsade de pointes (TdP) have been reported in postmarketing experience with lapatinib.
    Lefamulin: (Major) Avoid coadministration of lefamulin with leuprolide as concurrent use may increase the risk of QT prolongation. If coadministration cannot be avoided, monitor ECG during treatment. Lefamulin has a concentration dependent QTc prolongation effect. The pharmacodynamic interaction potential to prolong the QT interval of the electrocardiogram between lefamulin and other drugs that effect cardiac conduction is unknown. Androgen deprivation therapy (i.e., leuprolide) may prolong the QT/QTc interval.
    Lenvatinib: (Major) Avoid coadministration of lenvatinib with leuprolide due to the risk of QT prolongation. Prolongation of the QT interval has been reported with lenvatinib therapy. Androgen deprivation therapy (i.e., leuprolide) may prolong the QT/QTc interval.
    Levalbuterol: (Minor) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving short-acting beta-agonists. Androgen deprivation therapy may prolong the QT/QTc interval. Beta-agonists may also be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Levofloxacin: (Moderate) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving other QT prolonging agents. Androgen deprivation therapy (i.e., leuprolide) may prolong the QT/QTc interval. Levofloxacin has also been associated with a risk of QT prolongation and torsade de pointes (TdP). Although extremely rare, TdP has been reported during postmarketing surveillance of levofloxacin.
    Lithium: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving lithium. Lithium has been associated with QT prolongation. Androgen deprivation therapy may also prolong the QT/QTc interval.
    Lofexidine: (Moderate) Monitor ECGs for QT prolongation if coadministration of lofexidine with leuprolide is necessary. Lofexidine prolongs the QT interval. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
    Long-acting beta-agonists: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving long-acting beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. Androgen deprivation therapy may also prolong the QT/QTc interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Loperamide: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving loperamide. 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 may also prolong the QT/QTc interval.
    Loperamide; Simethicone: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving loperamide. 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 may also prolong the QT/QTc interval.
    Lopinavir; Ritonavir: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving lopinavir. Lopinavir; ritonavir is associated with QT prolongation. Androgen deprivation therapy may also prolong the QT/QTc interval. Coadministration may result in additive QT prolongation.
    Lorcaserin: (Major) Avoid coadministration of leuprolide with lorcaserin due to the risk of reduced efficacy of leuprolide. Lorcaserin can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog.
    Loxapine: (Major) Avoid coadministration of leuprolide with loxapine due to the risk of reduced efficacy of leuprolide. Loxapine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog.
    Macimorelin: (Major) Avoid concurrent administration of macimorelin with drugs that prolong the QT interval, such as leuprolide. Use of these drugs together may increase the risk of developing torsade de pointes-type ventricular tachycardia. Sufficient washout time of drugs that are known to prolong the QT interval prior to administration of macimorelin is recommended. Treatment with macimorelin has been associated with an increase in the corrected QT (QTc) interval. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
    Maprotiline: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving maprotiline. 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) tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Androgen deprivation therapy may also prolong the QT/QTc interval. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs.
    Mefloquine: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving mefloquine as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy may prolong the QT/QTc interval. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation.
    Meperidine; Promethazine: (Major) Avoid coadministration of leuprolide with promethazine due to the risk of reduced efficacy of leuprolide; QT prolongation may also occur. Promethazine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog. Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
    Metaproterenol: (Minor) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving short-acting beta-agonists. Androgen deprivation therapy may prolong the QT/QTc interval. Beta-agonists may also be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Methadone: (Major) Coadministration of methadone with leuprolide should be undertaken with extreme caution and a careful assessment of the benefits of therapy versus the risks of QT prolongation. Methadone is associated with an increased risk for QT prolongation and torsade de pointes (TdP), especially at higher doses (greater than 200 mg/day but averaging approximately 400 mg/day in adult patients). Most cases involve patients being treated for pain with large, multiple daily doses of methadone, although cases have been reported in patients receiving doses commonly used for maintenance treatment of opioid addiction. Androgen deprivation therapy may prolong the QT/QTc interval.
    Methyldopa: (Major) Avoid coadministration of leuprolide with methyldopa due to the risk of reduced efficacy of leuprolide. Methyldopa can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog.
    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: (Major) Avoid coadministration of leuprolide with metoclopramide due to the risk of reduced efficacy of leuprolide. Metoclopramide can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog.
    Metronidazole: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving metronidazole. Potential QT prolongation has been reported in limited case reports with metronidazole. Androgen deprivation therapy may also prolong the QT/QTc interval.
    Midostaurin: (Major) Consider periodic monitoring of EGCs for QT prolongation if coadministration of leuprolide and midostaurin is necessary. Prolongation of the QT interval was reported in patients who received midostaurin in clinical trials. Androgen deprivation therapy (i.e., leuprolide ) may also prolong the QT/QTc interval.
    Mifepristone: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving mifepristone. To minimize the risk of QT prolongation, the lowest effective dose of mifepristone should always be used. Mifepristone has been associated with dose-dependent prolongation of the QT interval. Androgen deprivation therapy may prolong the QT/QTc interval.
    Mirtazapine: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving mirtazapine. Mirtazapine has been associated with dose-dependent prolongation of the QT interval. Torsade de pointes (TdP) has been reported in postmarketing experience, primarily in overdose or in patients with other risk factors for QT prolongation. Androgen deprivation therapy may also prolong the QT/QTc interval.
    Molindone: (Major) Avoid coadministration of leuprolide with molindone due to the risk of reduced efficacy of leuprolide. Molindone can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog.
    Moxifloxacin: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving moxifloxacin. Quinolones have been associated with a risk of QT prolongation. Although extremely rare, torsade de pointes (TdP) has been reported during postmarketing surveillance of moxifloxacin; these reports generally involved patients with concurrent medical conditions or concomitant medications that may have been contributory. Androgen deprivation therapy may also prolong the QT/QTc interval.
    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) Avoid administration of nilotinib with leuprolide due to the risk of QT interval prolongation. Sudden death and QT prolongation have occurred in patients who received nilotinib therapy. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
    Nortriptyline: (Minor) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving tricyclic antidepressants (TCAs). Tricyclic antidepressants 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). Androgen deprivation therapy may also prolong the QT/QTc interval.
    Octreotide: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving octreotide. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy. Since bradycardia is a risk factor for development of torsade de pointes (TdP), the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval. Androgen deprivation therapy may prolong the QT/QTc interval.
    Ofloxacin: (Moderate) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving leuprolide as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy (i.e., leuprolide) may prolong the QT/QTc interval. Ofloxacin has been associated with a risk of QT prolongation and torsade de pointes (TdP). Although extremely rare, TdP has been reported during postmarketing surveillance of ofloxacin.
    Olanzapine: (Major) Avoid coadministration of leuprolide with olanzapine due to the risk of reduced efficacy of leuprolide; QT prolongation may also occur. Olanzapine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
    Olodaterol: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving long-acting beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. Androgen deprivation therapy may also prolong the QT/QTc interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Ondansetron: (Major) Monitor ECGs for QT prolongation if coadministration of ondansetron with leuprolide is necessary. Ondansetron has been associated with a dose-related increase in the QT interval and postmarketing reports of torsade de pointes (TdP). Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
    Osimertinib: (Major) Avoid coadministration of leuprolide with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
    Oxaliplatin: (Major) Monitor ECGs for QT prolongation and monitor electrolytes in patients receiving oxaliplatin concomitantly with leuprolide; correct electrolyte abnormalities prior to administration of oxaliplatin. Prolongation of the QT interval and ventricular arrhythmias including fatal torsade de pointes (TdP) have been reported with oxaliplatin use in postmarketing experience. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc 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) Avoid coadministration of leuprolide with paliperidone due to the risk of reduced efficacy of leuprolide and the risk of QT prolongation. Paliperidone can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog. Paliperidone has been associated with QT prolongation; torsade de pointes (TdP) and ventricular fibrillation have been reported in the setting of overdose. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
    Panobinostat: (Major) Coadministration of panobinostat with leuprolide is not recommended due to the risk of QT prolongation. Prolongation of the QT interval has been reported with panobinostat treatment. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
    Pasireotide: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving pasireotide as concurrent use may increase the risk of QT prolongation. Prolongation of the QT interval has occurred with pasireotide at therapeutic and supra-therapeutic doses. Androgen deprivation therapy may also prolong the QT/QTc interval.
    Pazopanib: (Major) Coadministration of pazopanib and leuprolide is not advised due to the risk of QT prolongation. If concomitant use is unavoidable, closely monitor ECGs for QT interval prolongation. Pazopanib has been reported to prolong the QT interval. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
    Pentamidine: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving pentamidine. Systemic pentamidine has been associated with QT prolongation. Androgen deprivation therapy may prolong the QT/QTc interval.
    Perphenazine: (Major) Avoid coadministration of leuprolide with perphenazine due to the risk of reduced efficacy of leuprolide; QT prolongation may also occur. Perphenazine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog. Perphenazine is associated with a possible risk for QT prolongation. Theoretically, perphenazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
    Perphenazine; Amitriptyline: (Major) Avoid coadministration of leuprolide with perphenazine due to the risk of reduced efficacy of leuprolide; QT prolongation may also occur. Perphenazine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog. Perphenazine is associated with a possible risk for QT prolongation. Theoretically, perphenazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval. (Minor) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving tricyclic antidepressants (TCAs). Tricyclic antidepressants 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). Androgen deprivation therapy may also prolong the QT/QTc interval.
    Phenylephrine; Promethazine: (Major) Avoid coadministration of leuprolide with promethazine due to the risk of reduced efficacy of leuprolide; QT prolongation may also occur. Promethazine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog. Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
    Pimavanserin: (Major) Coadministration of pimavanserin with leuprolide should generally be avoided due to the risk of QT prolongation. Pimavanserin may cause QT prolongation. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
    Pimozide: (Severe) Because of the potential for torsade de pointes (TdP), use of leuprolide with pimozide is contraindicated; the efficacy of leuprolide may also be reduced. Pimozide is associated with a well-established risk of QT prolongation and TdP. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval. Pimozide can also cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog.
    Pirbuterol: (Minor) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving short-acting beta-agonists. Androgen deprivation therapy may prolong the QT/QTc interval. Beta-agonists may also be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Pitolisant: (Major) Avoid coadministration of pitolisant with leuprolide as concurrent use may increase the risk of QT prolongation. Pitolisant prolongs the QT interval. Androgen deprivation therapy (i.e., leuprolide) may prolong the QT/QTc interval.
    Posaconazole: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving posaconazole as concurrent use may increase the risk of QT prolongation. Posaconazole has been associated with prolongation of the QT interval as well as rare cases of torsade de pointes (TdP). Androgen deprivation therapy may also prolong the QT/QTc 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: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving primaquine as concurrent use may increase the risk of QT prolongation. Primaquine has the potential to cause QT prolongation. Androgen deprivation therapy may also prolong the QT/QTc interval.
    Procainamide: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving procainamide. Procainamide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Androgen deprivation therapy may also prolong the QT/QTc interval.
    Prochlorperazine: (Major) Avoid coadministration of leuprolide with prochlorperazine due to the risk of reduced efficacy of leuprolide; QT prolongation may also occur. Prochlorperazine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog. Prochlorperazine is associated with a possible risk for QT prolongation. Theoretically, prochlorperazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
    Promethazine: (Major) Avoid coadministration of leuprolide with promethazine due to the risk of reduced efficacy of leuprolide; QT prolongation may also occur. Promethazine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog. Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
    Propafenone: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving propafenone. Propafenone is a Class IC antiarrhythmic which increases the QT interval, but largely due to prolongation of the QRS interval. Androgen deprivation therapy may also prolong the QT/QTc interval.
    Protriptyline: (Minor) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving tricyclic antidepressants (TCAs). Tricyclic antidepressants 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). Androgen deprivation therapy may also prolong the QT/QTc interval.
    Quetiapine: (Major) Avoid coadministration of quetiapine with leuprolide due to the risk of QT prolongation. Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
    Quinidine: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving quinidine. Quinidine administration is associated with QT prolongation and torsade de pointes (TdP). Androgen deprivation therapy may also prolong the QT/QTc interval.
    Quinine: (Major) Avoid coadministration of quinine with leuprolide due to the risk of QT prolongation and torsade de pointes (TdP). Quinine has been associated with QT prolongation and rare cases of TdP. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
    Ramelteon: (Major) Avoid coadministration of leuprolide with ramelteon due to the risk of reduced efficacy of leuprolide. Ramelteon can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog.
    Ranolazine: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving ranolazine as concurrent use may increase the risk of QT prolongation. Ranolazine is associated with dose- and plasma concentration-related increases in the QTc interval. Androgen deprivation therapy may prolong the QT/QTc interval. Ranolazine is associated with dose- and plasma concentration-related increases in the QTc interval. Although there are no studies examining the effects of ranolazine in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation.
    Reserpine: (Major) Avoid coadministration of leuprolide with reserpine due to the risk of reduced efficacy of leuprolide. Reserpine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog.
    Ribociclib: (Major) Avoid coadministration of ribociclib with leuprolide due to the risk of QT prolongation. Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. Ribociclib-related ECG changes typically occurred within the first four weeks of treatment and were reversible with dose interruption. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
    Ribociclib; Letrozole: (Major) Avoid coadministration of ribociclib with leuprolide due to the risk of QT prolongation. Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. Ribociclib-related ECG changes typically occurred within the first four weeks of treatment and were reversible with dose interruption. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
    Rilpivirine: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving rilpivirine as concurrent use may increase the risk of QT prolongation. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Androgen deprivation therapy may also prolong the QT/QTc interval.
    Risperidone: (Major) Avoid coadministration of leuprolide with risperidone due to the risk of reduced efficacy of leuprolide; QT prolongation may also occur. Risperidone can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
    Romidepsin: (Moderate) Monitor ECGs and monitor electrolytes at baseline and periodically during treatment if coadministration of romidepsin with leuprolide is necessary as concurrent use may increase the risk of QT prolongation. Romidepsin has been reported to prolong the QT interval. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
    Salmeterol: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving long-acting beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. Androgen deprivation therapy may also prolong the QT/QTc interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Saquinavir: (Major) Avoid coadministration of saquinavir with leuprolide if possible due to the risk of QT prolongation. If concomitant use is unavoidable, perform a baseline ECG prior to initiation of therapy and carefully follow monitoring recommendations. Saquinavir boosted with ritonavir increases the QT interval in a dose-dependent fashion, which may increase the risk for serious arrhythmias such as torsade de pointes (TdP). Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
    Sertraline: (Moderate) Consider whether the benefits of leuprolide therapy outweigh the potential risk of QT prolongation in patients receiving sertraline. If use together is necessary, use caution and monitor patients for QT prolongation. Androgen deprivation therapy (i.e., leuprolide) may prolong the QT/QTc interval. Sertraline's FDA-approved labeling recommends avoiding concomitant use with drugs known to prolong the QTc interval; however, the risk of sertraline-induced QT prolongation is generally considered to be low in clinical practice. Its effect on QTc interval is minimal (typically less than 5 msec), and the drug has been used safely in patients with cardiac disease (e.g., recent myocardial infarction, unstable angina, chronic heart failure).
    Sevoflurane: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving halogenated anesthetics. Androgen deprivation therapy may prolong the QT/QTc interval. Halogenated anesthetics can also prolong the QT interval.
    Short-acting beta-agonists: (Minor) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving short-acting beta-agonists. Androgen deprivation therapy may prolong the QT/QTc interval. Beta-agonists may also be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Siponimod: (Major) In general, do not initiate treatment with siponimod in patients receiving leuprolide due to the potential for QT prolongation. Consult a cardiologist regarding appropriate monitoring if siponimod use is required. Siponimod therapy prolonged the QT interval at recommended doses in a clinical study. Androgen deprivation therapy (i.e., leuprolide) may prolong the QT/QTc interval.
    Solifenacin: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving solifenacin. Solifenacin has been associated with dose-dependent prolongation of the QT interval; torsade de pointes (TdP) has been reported with postmarketing use, although causality was not determined. Androgen deprivation therapy may also prolong the QT/QTc interval.
    Sorafenib: (Major) Monitor ECGs for QT prolongation and monitor electrolytes if coadministration of sorafenib with leuprolide is necessary; correct any electrolyte abnormalities. An interruption or discontinuation of sorafenib therapy may be necessary if QT prolongation occurs. Sorafenib has been associated with QT prolongation. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
    Sotalol: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving sotalol. Sotalol administration is associated with QT prolongation and torsade de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. Androgen deprivation therapy may also prolong the QT/QTc interval.
    Sunitinib: (Moderate) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving sunitinib as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy (i.e., leuprolide) may prolong the QT/QTc interval. Sunitinib can prolong the QT interval.
    Tacrolimus: (Moderate) Consider the benefits of androgen deprivation therapy and monitor ECG and electrolytes periodically during treatment if tacrolimus is administered with leuprolide. Tacrolimus may prolong the QT interval and cause torsade de pointes (TdP). Androgen deprivation therapy (i.e., leuprolide) may prolong the QT/QTc interval.
    Tamoxifen: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving tamoxifen. 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 may prolong the QT/QTc interval.
    Telavancin: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving telavancin as concurrent use may increase the risk of QT prolongation. Telavancin has been associated with QT prolongation. Androgen deprivation therapy may also prolong the QT/QTc interval.
    Telithromycin: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving telithromycin as concurrent use may increase the risk of QT prolongation. Telithromycin is associated with QT prolongation and torsade de pointes (TdP). Androgen deprivation therapy may prolong the QT/QTc interval.
    Terbutaline: (Minor) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving short-acting beta-agonists. Androgen deprivation therapy may prolong the QT/QTc interval. Beta-agonists may also be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    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) Avoid coadministration of leuprolide with tetrabenazine due to the risk of reduced efficacy of leuprolide; QT prolongation may also occur. Tetrabenazine can cause leuprolide, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; goserelin is a GnRH analog. Tetrabenazine also causes a small increase in the corrected QT interval (QTc). Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
    Thioridazine: (Severe) Because of the potential for torsade de pointes (TdP), use of leuprolide with thioridazine is contraindicated; the efficacy of leuprolide may also be reduced. Thioridazine is associated with a well-established risk of QT prolongation and TdP and is considered contraindicated for use along with agents that may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval. Thioridazine can also cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog.
    Thiothixene: (Major) Avoid coadministration of leuprolide with thiothixene due to the risk of reduced efficacy of leuprolide. Thiothixene can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog.
    Tiotropium; Olodaterol: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving long-acting beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. Androgen deprivation therapy may also prolong the QT/QTc interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Tolterodine: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving tolterodine. Tolterodine has been associated with dose-dependent prolongation of the QT interval, especially in poor CYP2D6 metabolizers. Androgen deprivation therapy may also prolong the QT/QTc interval.
    Toremifene: (Major) Avoid coadministration of leuprolide with toremifene due to the risk of additive QT prolongation. If concomitant use is unavoidable, closely monitor ECGs for QT prolongation and monitor electrolytes. Toremifene has been shown to prolong the QTc interval in a dose- and concentration-related manner. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
    Trandolapril; Verapamil: (Major) Avoid coadministration of leuprolide with verapamil due to the risk of reduced efficacy of leuprolide. Verapamil can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog.
    Trazodone: (Major) Avoid coadministration of trazodone with leuprolide due to the risk of QT prolongation. Trazodone can prolong the QT/QTc interval at therapeutic doses; in addition, there are postmarketing reports of torsade de pointes (TdP). Androgen deprivation therapy (i.e., leuprolide) may prolong the QT/QTc interval.
    Tricyclic antidepressants: (Minor) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving tricyclic antidepressants (TCAs). Tricyclic antidepressants 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). Androgen deprivation therapy may also prolong the QT/QTc interval.
    Trifluoperazine: (Major) Avoid coadministration of leuprolide with trifluoperazine due to the risk of reduced efficacy of leuprolide; QT prolongation may also occur. Trifluoperazine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog. Trifluoperazine is also associated with a possible risk for QT prolongation. Theoretically, trifluoperazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
    Trimipramine: (Minor) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving tricyclic antidepressants (TCAs). Tricyclic antidepressants 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). Androgen deprivation therapy may also prolong the QT/QTc interval.
    Umeclidinium; Vilanterol: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving long-acting beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. Androgen deprivation therapy may also prolong the QT/QTc interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Vandetanib: (Major) Avoid coadministration of vandetanib with leuprolide due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. 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 (i.e., leuprolide) may also prolong the QT/QTc interval.
    Vardenafil: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving vardenafil as concurrent use may increase the risk of QT prolongation. Both therapeutic and supratherapeutic doses of vardenafil produce an increase in QTc interval. Androgen deprivation therapy may also prolong the QT/QTc interval.
    Vemurafenib: (Major) Closely monitor ECGs for QT prolongation if coadministration of vemurafenib with leuprolide is necessary. Vemurafenib has been associated with QT prolongation. Androgen deprivation therapy (i.e., leuprolide) may prolong the QT/QTc interval.
    Venlafaxine: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving venlafaxine. Venlafaxine administration is associated with a possible risk of QT prolongation; torsade de pointes (TdP) has reported with postmarketing use. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
    Verapamil: (Major) Avoid coadministration of leuprolide with verapamil due to the risk of reduced efficacy of leuprolide. Verapamil can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog.
    Voriconazole: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving voriconazole as concurrent use may increase the risk of QT prolongation. Voriconazole has been associated with QT prolongation and rare cases of torsade de pointes. Androgen deprivation therapy may also prolong the QT/QTc interval.
    Vorinostat: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving vorinostat. Vorinostat therapy is associated with a risk of QT prolongation. Androgen deprivation therapy may also prolong the QT/QTc interval.
    Ziprasidone: (Major) Concomitant use of ziprasidone and leuprolide should be avoided due to a potential for additive QT prolongation. Clinical trial data indicate that ziprasidone causes QT prolongation; there are postmarketing reports of torsade de pointes (TdP) in patients with multiple confounding factors. Androgen deprivation therapy (i.e., leuprolide) may prolong the QT/QTc interval.

    PREGNANCY AND LACTATION

    Pregnancy

    Because the consequences on lactation and 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%.