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    Leuprolide

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    Apr.07.2024

    Leuprolide

    Indications/Dosage

    Labeled

    • endometriosis
    • precocious puberty
    • prostate cancer
    • uterine leiomyomata

    Off-Label

    • benign prostatic hyperplasia (BPH)
    • breast cancer
    • fertility preservation
    • infertility
    • premenstrual syndrome (PMS)
    • stuttering priapism
    † Off-label indication

    For the treatment of benign prostatic hyperplasia (BPH)†

    Subcutaneous dosage (injection solution)

    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.[24155]

    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.[24156]

    For the treatment of prostate cancer

    for the treatment of advanced prostate cancer

    Subcutaneous dosage (leuprolide acetate for injectable suspension [Eligard 1-Month])

    Adults

    7.5 mg subcutaneously once monthly. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. In a multicenter, open-label study, the mean testosterone concentration on day 28 after treatment with once-monthly subcutaneous leuprolide acetate was 21.8 ng/dL; 94.1% of patients had testosterone concentrations below the castrate threshold (50 ng/dL) at day 28 and 100% were below the castrate threshold at day 42. There were no breakthrough occurrences of testosterone concentration greater than 50 ng/dL at any time point after testosterone suppression was achieved.[45097]

    Subcutaneous dosage (leuprolide acetate for injectable suspension [Eligard 3-Month])

    Adults

    22.5 mg subcutaneously every 3 months. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. In a multicenter, open-label study, the mean testosterone concentration on day 21 after treatment with every3-month subcutaneous leuprolide acetate was 27.7 ng/dL; 99% of patients had testosterone concentrations below the castrate threshold (50 ng/dL) at day 28 and 100% were below the castrate threshold at day 35. Once testosterone suppression was achieved, one patient (less than 1%) demonstrated breakthrough (testosterone concentration greater than 50 ng/dL) following the initial injection; that patient remained below the castrate threshold following the second injection.[45097]

    Subcutaneous dosage (leuprolide acetate for injectable suspension [Eligard 4-Month])

    Adults

    30 mg subcutaneously every 4 months. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. In a multicenter, open-label study, the mean testosterone concentration on day 28 after treatment with once-monthly subcutaneous leuprolide acetate was 17.2 ng/dL; 96% of patients had testosterone concentrations below the castrate threshold (50 ng/dL) at day 28 and 100% were below the castrate threshold at day 42. Three patients (3%) demonstrated breakthrough testosterone concentrations (greater than 50 ng/dL) after the second injection once testosterone suppression was achieved; castrate suppression was reached again up to 18 days after the second injection and was maintained thereafter in all 3 patients.[45097]

    Subcutaneous dosage (leuprolide acetate for injectable suspension [Eligard 6-Month])

    Adults

    45 mg subcutaneously every 6 months. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. In a multicenter, open-label study, the mean testosterone concentration on day 28 after treatment with once-monthly subcutaneous leuprolide acetate was 16.7 ng/dL; 99.1% of patients had testosterone concentrations below the castrate threshold (50 ng/dL) at day 28. One patient (less than 1%) demonstrated a breakthrough testosterone concentration (greater than 50 ng/dL) once testosterone suppression was achieved. This patient reached castrate suppression at day 21 and remained suppressed until day 308 (testosterone concentration, 112 ng/dL); at day 336, his testosterone concentration was 210 ng/dL.[45097]

    Subcutaneous dosage (leuprolide mesylate emulsion [Camcevi])

    Adults

    42 mg subcutaneously once every 6 months. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. After the first injection of leuprolide mesylate, serum testosterone concentrations were suppressed to 50 ng/dL or less by week 4 in 98.5% of patients with advanced prostate cancer and a baseline serum testosterone concentration greater than 150 ng/dL in a multinational, single-arm study; serum testosterone was 50 ng/dL or less from week 4 to week 48 in 97% of patients. Serum testosterone concentrations were 20 ng/dL or less on day 28 in 69.3% of patients.[66709] [66714]

    Intramuscular dosage (leuprolide acetate for depot suspension [Lupron Depot 1-Month])

    Adults

    7.5 mg IM every 4 weeks. Do not use concurrently a fractional dose, or a combination of doses of this or any depot formulation due to different release characteristics. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. In a multicenter, noncomparative trial, patients with previously untreated stage D2 prostate cancer received leuprolide as a once-monthly IM depot injection. Serum testosterone increased by 50% or more above baseline during the first week of treatment in the majority of patients; it was suppressed to castrate levels within 30 days in 94% of patients and within 66 days in all patients. One patient had a breakthrough testosterone concentration (greater than 50 ng/dL) that was associated with a substantial dosing delay.[43800]

    Intramuscular dosage (leuprolide acetate for depot suspension [Lupron Depot 3-Month])

    Adults

    22.5 mg IM every 12 weeks. Do not use concurrently a fractional dose, or a combination of doses of this or any depot formulation due to different release characteristics. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. In clinical studies, serum testosterone was suppressed to castrate levels within 30 days in 95% of patients; one patient later experienced a transient minimal elevation of testosterone. During the initial 24 weeks of treatment, 85% of patients did not progress.[43800] [68727]

    Intramuscular dosage (leuprolide acetate for depot suspension [Lupron Depot 4-Month])

    Adults

    30 mg IM every 16 weeks. Do not use concurrently a fractional dose, or a combination of doses of this or any depot formulation due to different release characteristics. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. In a multicenter, noncomparative trial, patients with previously untreated stage D2 prostate cancer were treated with leuprolide 30 mg IM every 4 months. Serum testosterone increased by 50% or more above baseline during the first week of treatment in the majority of patients; it was suppressed to castrate levels within 30 days in 94% of patients and within 43 days in all patients. Two patients had breakthrough testosterone concentrations (greater than 50 ng/dL) at week 16 and 17, respectively, which returned to castrate level by week 18.[43800]

    Intramuscular dosage (leuprolide acetate for depot suspension [Lupron Depot 6-Month])

    Adults

    45 mg IM every 24 weeks. Do not use concurrently a fractional dose, or a combination of doses of this or any depot formulation due to different release characteristics. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. In a multicenter, noncomparative trial, patients with prostate cancer were treated with leuprolide 45 mg IM every 24 weeks. Serum testosterone was suppressed to castrate levels (less than 50 ng/dL) from week 4 through week 48 in 93.4% of patients; 8 patients had breakthrough testosterone concentrations (greater than 50 ng/dL).[43800]

    for the palliative treatment of advanced prostate cancer

    Subcutaneous dosage (leuprolide acetate for injection [Lupron and generic equivalents])

    Adults

    1 mg subcutaneously once daily. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. In a controlled study, the survival rate for leuprolide acetate 1 mg subcutaneously once daily was comparable to diethylstilbestrol (DES) 3 mg daily in patients with advanced prostate cancer after 2 years of treatment; the objective response to treatment was also similar for the 2 groups.[66721]

    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).[45417]

    For the management of endometriosis including pain relief and reduction of endometriotic lesions

    Intramuscular dosage (injection suspension)

    Adults

    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.[42683] [51299] Clinical guidelines/studies suggest the addition of hormonal add-back therapy 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.[69730]

    For the treatment of central precocious puberty

    NOTE: Leuprolide has been designated an orphan drug by the FDA for this indication.

    for the treatment of central precocious puberty as a once monthly regimen

    Intramuscular dosage (injection suspension, Lupron Depot-Ped 1-month)

    Children weighing more than 37.5 kg

    15 mg IM every 4 weeks. May adjust dose if changes in body weight occur. Max: 15 mg/dose. Monitor hormonal and clinical parameters at month 1 to 2, with dose changes, and further as clinically appropriate to ensure adequate suppression. In the case of inadequate suppression, consider other available GnRH agonists indicated for the treatment of central precocious puberty.[41676]

    Children weighing more than 25 kg to 37.5 kg

    11.25 mg IM every 4 weeks. Increase the dose to the next available higher dose (e.g., 15 mg) at next monthly injection if inadequate hormonal and clinical suppression with starting dose. May adjust dose if changes in body weight occur. Max: 15 mg/dose. Monitor hormonal and clinical parameters at month 1 to 2, with dose changes, and further as clinically appropriate to ensure adequate suppression.[41676]

    Children weighing 25 kg or less

    7.5 mg IM every 4 weeks. Increase the dose to the next available higher dose (e.g., 11.25 mg) at next monthly injection if inadequate hormonal and clinical suppression with the starting dose. May adjust dose if changes in body weight occur. Max: 15 mg/dose. Monitor hormonal and clinical parameters at month 1 to 2, with dose changes, and further as clinically appropriate to ensure adequate suppression.[41676]

    for the treatment of central precocious puberty as an every 3 months regimen

    Intramuscular dosage (injection suspension, Lupron Depot-Ped 3-month)

    Children

    11.25 or 30 mg IM every 12 weeks. Monitor hormonal and clinical parameters at month 2 to 3, month 6, and further as clinically appropriate to ensure adequate suppression. In the case of inadequate suppression, consider other available GnRH agonists indicated for the treatment of central precocious puberty.[41676]

    for the treatment of central precocious puberty as an every 6 months regimen

    Subcutaneous dosage (injection suspension, Fensolvi)

    Children 2 to 12 years

    45 mg subcutaneously every 6 months. Monitor hormonal and clinical parameters at month 1 to 2 and further as clinically appropriate to ensure adequate suppression. In the case of inadequate suppression, consider other available GnRH agonists indicated for the treatment of central precocious puberty.[65368]

    Intramuscular dosage (injection suspension, Lupron Depot-Ped 6-month)

    Children

    45 mg IM every 6 months. Monitor hormonal and clinical parameters at months 5 to 6 and further as clinically appropriate to ensure adequate suppression. In the case of inadequate suppression, consider other available GnRH agonists indicated for the treatment of central precocious puberty.[41676]

    for the treatment of central precocious puberty as a once daily regimen†

    Subcutaneous dosage (solution for injection)

    Children

    50 mcg/kg/dose subcutaneously once daily. Monitor hormonal and clinical parameters at month 1 to 2, with dose changes, and further as clinically appropriate during therapy to ensure adequate suppression. In the case of inadequate suppression, the dose may be increased by 10 mcg/kg/day.[45475] [70160]

    For the treatment of anemia due to uterine leiomyomata (fibroids) in combination with iron therapy preoperatively in persons for whom 3 months of hormonal suppression is deemed necessary

    Intramuscular dosage (Lupron Depot 1-Month)

    Adults

    3.75 mg IM once monthly for up to 3 months. Leuprolide is not indicated for combination use with norethindrone acetate add-back therapy. Leuprolide acetate depot 3.75 mg has different release characteristics than leuprolide acetate depot 11.25 mg and is dosed differently. Do not substitute products.[51299]

    Intramuscular dosage (Lupron Depot 3-Month)

    Adults

    11.25 mg IM as a single dose, which provides a 3-month treatment course. Leuprolide is not indicated for combination use with norethindrone acetate add-back therapy. Leuprolide acetate depot 11.25 mg has different release characteristics than leuprolide acetate depot 3.75 mg and is dosed differently. Do not substitute products.[43800]

    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.[24165] 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†

    Subcutaneous dosage for 'long-protocol' (leuprolide acetate injection solution only, do NOT use depot formulations)

    Adult females

    Optimal daily dosage is individualized by the ART specialist; 'long-protocols' are most common but an alternative leuprolide 'flare protocol' is also used (not discussed here, such dosage regimens for flare protocols are much different than those of long protocols). In the long protocol, leuprolide is typically started on day 22 or 23 of the menstrual cycle prior to the ovarian stimulation cycle; dosages vary with usual range 0.5 to 1 mg per day subcutaneously. 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 are administered until sufficient follicular development is attained. HCG is then administered to induce final follicular maturation for oocyte retrieval. FDA-approved medicines like ganirelix and cetrorelix are now more commonly used for this purpose.[63289]

    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.[34288] 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.[34289] 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.[34290]

    For fertility preservation† prior to chemotherapy

    Intramuscular dosage

    Adults

    3.75 mg IM every 4 weeks. When used in patients undergoing chemotherapy, leuprolide is usually initiated about 2 weeks prior to chemotherapy.[65690] [65692] [65693] [65694] When proven fertility preservation methods are not feasible, and in the setting of young women with breast cancer, gonadotropin-releasing hormone agonists (GnRHa) may be offered to patients in the hope of reducing the likelihood of chemotherapy-induced ovarian insufficiency.[65695] [65696]

    Adolescents

    3.75 mg IM every 4 weeks. In one trial, leuprolide injection solution 0.2 mg/day subcutaneously was given daily during the first 2 weeks of treatment so chemotherapy could be started immediately.[65691] When proven fertility preservation methods are not feasible, and in the setting of young women with breast cancer, gonadotropin-releasing hormone agonists (GnRHa) may be offered to patients in the hope of reducing the likelihood of chemotherapy-induced ovarian insufficiency.[65695] [65696]

    Therapeutic Drug Monitoring

    Maximum Dosage Limits

    • Adults

      Leuprolide mesylate (Camcevi)

      Prostate Cancer: 42 mg subcutaneously every 6 months.

      Leuprolide acetate for injectable suspension (Eligard)

      Prostate Cancer: 7.5 mg subcutaneously once monthly; OR 22.5 mg subcutaneously every 3 months; OR 30 mg subcutaneously every 4 months; OR 45 mg subcutaneously every 6 months.

      Leuprolide acetate for solution (Lupron)

      Prostate Cancer: 1 mg subcutaneously once daily.

      Leuprolide acetate for depot suspension (Lupron Depot)

      Prostate Cancer: 7.5 mg IM once monthly; OR 22.5 mg IM every 3 months; OR 30 mg IM every 4 months; OR 45 mg IM every 6 months.

      Endometriosis or Fibroids: 3.75 mg IM once monthly; OR 11.25 mg IM every 3 months.

    • Geriatric

      Leuprolide mesylate (Camcevi)

      Prostate Cancer: 42 mg subcutaneously every 6 months.

      Leuprolide acetate for injectable suspension (Eligard)

      Prostate Cancer: 7.5 mg subcutaneously once monthly; OR 22.5 mg subcutaneously every 3 months; OR 30 mg subcutaneously every 4 months; OR 45 mg subcutaneously every 6 months.

      Leuprolide acetate for solution (Lupron)

      Prostate Cancer: 1 mg subcutaneously once daily.

      Leuprolide acetate for depot suspension (Lupron Depot)

      Prostate Cancer: 7.5 mg IM once monthly; OR 22.5 mg IM every 3 months; OR 30 mg IM every 4 months; OR 45 mg IM every 6 months.

      Endometriosis or Fibroids: 3.75 mg IM once monthly; OR 11.25 mg IM every 3 months.

    • Adolescents

      Safety and efficacy have not been established.

    • Children

      Leuprolide acetate for injectable suspension (Fensolvi)

      45 mg subcutaneously every 6 months.

      Leuprolide acetate for depot suspension (Lupron Depot-Ped)

      Once monthly regimen:

      Weight greater than 37.5 kg: 15 mg IM once monthly.

      Weight 26 kg up to 37.5 kg: 11.25 mg IM once monthly.

      Weight 25 kg or less: 7.5 mg IM once monthly.

      Once every 3 months regimen:

      30 mg IM every 3 months

      Once every 6 months regimen:

      45 mg IM every 6 months

    • Infants

      The safety and efficacy of leuprolide acetate has not been established in children younger than 2 years (Fensolvi) or 1 year (Lupron Depot-Ped).

      The safety and efficacy of leuprolide mesylate has not been established in children.

    Patients with Hepatic Impairment Dosing

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

    Patients with Renal Impairment Dosing

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

    † Off-label indication
    Revision Date: 04/07/2024, 02:01:29 PM

    References

    24155 - Oesterling JE. LHRH agonists. A nonsurgical treatment for benign prostatic hyperplasia. J Androl 1991;12:381-8.24156 - Eri LM, Tveter KJ. A prospective, placebo-controlled study of the luteinizing hormone-releasing hormone agonist leuprolide as treatment for patients with benign prostatic hyperplasia. J Urol 1993;150:359-64.24165 - Smith S, Schiff I. The premenstrual syndrome - diagnosis and management. Fertility and Sterility 1989;52:527-43.34288 - Levine LA, Guss SP. Gonadotropin-releasing hormone analogues in the treatment of sickle cell anemia-associated priapism. J Urol 1993;150:475-7.34289 - Steinberg J, Eyre RC. Management of recurrent priapism with epinephrine self-injection and gonadotropin-releasing hormone analogue. J Urol 1995;153:152-3.34290 - Montague DK, Jarow J, Broderick GA, et al. American Urological Association guideline on the management of priapism. J Urol 2003;170:1318-24.41676 - Lupron Depot-Ped (leuprolide acetate for depot suspension) package insert. North Chicago, IL: Abbott Laboratories; 2023 April.42683 - Lupron Depot-3 month 11.25 mg (leuprolide acetate injection, powder, lyophilized, for suspension) package insert. Osaka, Japan: Takeda Pharmaceutical Company Limited; 2019 March.43800 - Lupron Depot (leuprolide acetate for depot suspension) package insert. North Chicago, IL: AbbVie Inc; 2024 March.45097 - Eligard (leuprolide acetate) package insert. Fort Collins, CO: Tolmar, Inc.; 2024 Jan.45417 - Schmid P, Untch M, Kosse V, et al. Leuprolide acetate every-3-months depot versus cyclophosphamide, methotrexate, fluorouracil as adjuvant treatment in premenopausal patients with node-positive breast cancer: the TABLE Study. J Clin Oncol 2007;25:2509-2515.45475 - Leuprolide acetate package insert. Detroit, MI: Caraco, a Division of Sun Pharma Global Inc.; 2011 April.51299 - Lupron Depot 1 month 3.75 mg (leuprolide acetate) suspension package insert. Osaka, Japan: Takeda Pharmaceutical Company Limited; 2021 Jan.63289 - Fluker M, Grifo J, Leader A, et al. Efficacy and safety of ganirelix acetate versus leuprolide acetate in women undergoing controlled ovarian hyperstimulation. Fertil Steril 2001;75:38-45.65368 - Leuprolide acetate (Fensolvi) package insert. Fort Collins, CO: Tolmar, Inc.; 2022 April.65690 - Clowse ME, Behera MA, Anders CK, et al. Ovarian preservation by GnRH agonists during chemotherapy: a meta-analysis. J Womens Health 2009;18:311-19.65691 - Pereyra Pacheco B, Mendez Ribas JM, Milone G, et al. Use of GnRH analogs for functional protection of the ovary and preservation of fertility during cancer treatment in adolescents: a preliminary report. Gynecol Oncol 2001;81:391-7.65692 - Petri M, Brodsky R, Jones R, et al. High dose cyclophosphamide can cause ovarian failure. Arthritis Rheum 2004;50:408.65693 - Somers EC, Marder W, Christman GM,et al. Use of a Gonadotropin-Releasing Hormone Analog for Protection Against Premature Ovarian Failure During Cyclophosphamide Therapy in Women With Severe Lupus. Arthritis Rheum 2005;52:2761-7.65694 - Song G , Gao H, Yuan Z. Effect of Leuprolide Acetate on Ovarian Function After Cyclophosphamide-Doxorubicin-Based Chemotherapy in Premenopausal Patients With Breast Cancer: Results From a Phase II Randomized Trial. Med Oncol 2013;30:667.65695 - Oktay K, Harvey BE, Partridge AH, et al. Fertility Preservation in Patients With Cancer: ASCO Clinical Practice Guideline Update. J Clin Oncol. 2018;36:1994.65696 - Ethics Committee of the American Society for Reproductive Medicine. Fertility preservation and reproduction in patients facing gonadotoxic therapies: an Ethics Committee opinion. Fertil Steril 2018;110:380.66709 - Camcevi (leuprolide) injectable emulsion, for subcutaneous use package insert. Taiwan: Foresee Pharmaceuticals Co., Ltd.; 2024 March.66714 - Shore N, Mincik I, DeGuenther M, et al. A phase 3, open-label, multicenter study of a 6-month pre-mixed depot formulation of leuprolide mesylate in advanced prostate cancer patients. World Journal of Urology. 2020;38:111-119.66721 - Lupron (leuprolide acetate for injection) package insert. North Chicago, IL: AbbVie Inc; 2018 Dec.68727 - Lutrate Depot (leuprolide acetate for depot suspension) package insert. Warren, NJ: Cipla USA, Inc.; 2023 Feb.69730 - Becker CM, Bokor A, Heikinheimo O, et al. ESHRE guideline: endometriosis. Hum Reprod Open. 2022;2022:hoac009.70160 - U.S. Food and Drug Administration. Leuprolide supplemental new drug application information. FDA communication on removal of pediatric labeling for leuprolide acetate injection, 1 mg/0.2mL. Updated July 11, 2017. Available at: www.accessdata.fda.gov/drugsatfda_docs/appletter/2017/019010Orig1s039ltr.pdf. Accessed: January 15, 2023.

    How Supplied

    Leuprolide Acetate Implant

    Viadur 65mg Implant Kit (00026-9711) (Bayer Pharmaceuticals Corporation) (off market)

    Leuprolide Acetate Lyophilisate for suspension for injection

    Lupron Depot 1-Month 3.75mg Powder for Injection (00300-3641) (AbbVie US LLC) (off market)

    Leuprolide Acetate Lyophilisate for suspension for injection

    Lupron Depot 1-Month 3.75mg Powder for Injection (00300-3641) (TAP Pharmaceuticals Inc, a Takeda Company) (off market)Lupron Depot 1-Month 3.75mg Powder for Injection package photo

    Leuprolide Acetate Lyophilisate for suspension for injection

    Lupron Depot 1-Month 3.75mg Powder for Injection (00300-3132) (TAP Pharmaceuticals Inc, a Takeda Company) (off market)

    Leuprolide Acetate Lyophilisate for suspension for injection

    Lupron Depot 1-Month 7.5mg Powder for Injection (00300-3642) (AbbVie US LLC) (off market)

    Leuprolide Acetate Lyophilisate for suspension for injection

    Lupron Depot 1-Month 7.5mg Powder for Injection (00300-3642) (TAP Pharmaceuticals Inc, a Takeda Company) (off market)Lupron Depot 1-Month 7.5mg Powder for Injection package photo

    Leuprolide Acetate Lyophilisate for suspension for injection

    Lupron Depot 1-Month 7.5mg Powder for Injection (00300-3152) (TAP Pharmaceuticals Inc, a Takeda Company) (off market)

    Leuprolide Acetate Lyophilisate for suspension for injection

    Lupron Depot-Ped 7.5mg Powder for Injection (00300-2108) (AbbVie US LLC) (off market)

    Leuprolide Acetate Lyophilisate for suspension for injection

    Lupron Depot-Ped 7.5mg Powder for Injection (00300-2108) (TAP Pharmaceuticals Inc, a Takeda Company) (off market)Lupron Depot-Ped 7.5mg Powder for Injection package photo

    Leuprolide Acetate Lyophilisate for suspension for injection

    Lupron Depot-Ped 7.5mg Powder for Injection (00300-3154) (TAP Pharmaceuticals Inc, a Takeda Company) (off market)

    Leuprolide Acetate Lyophilisate for suspension for injection

    Lupron Depot 3-Month 11.25mg Powder for Injection (00300-3663) (AbbVie US LLC) (off market)

    Leuprolide Acetate Lyophilisate for suspension for injection

    Lupron Depot 3-Month 11.25mg Powder for Injection (00300-3662) (TAP Pharmaceuticals Inc, a Takeda Company) (off market)

    Leuprolide Acetate Lyophilisate for suspension for injection

    Lupron Depot 3-Month 11.25mg Powder for Injection (00300-3663) (TAP Pharmaceuticals Inc, a Takeda Company) (off market)Lupron Depot 3-Month 11.25mg Powder for Injection package photo

    Leuprolide Acetate Lyophilisate for suspension for injection

    Lupron Depot-Ped 11.25mg Powder for Injection (00300-2282) (AbbVie US LLC) (off market)Lupron Depot-Ped 11.25mg Powder for Injection package photo

    Leuprolide Acetate Lyophilisate for suspension for injection

    Lupron Depot-Ped 11.25mg Powder for Injection (00300-2282) (TAP Pharmaceuticals Inc, a Takeda Company) (off market)Lupron Depot-Ped 11.25mg Powder for Injection package photo

    Leuprolide Acetate Lyophilisate for suspension for injection

    Lupron Depot-Ped 11.25mg Powder for Injection (00300-3306) (TAP Pharmaceuticals Inc, a Takeda Company) (off market)

    Leuprolide Acetate Lyophilisate for suspension for injection

    Lupron Depot-Ped 15mg Powder for Injection (00300-2440) (AbbVie US LLC) (off market)

    Leuprolide Acetate Lyophilisate for suspension for injection

    Lupron Depot-Ped 15mg Powder for Injection (00300-2440) (TAP Pharmaceuticals Inc, a Takeda Company) (off market)Lupron Depot-Ped 15mg Powder for Injection package photo

    Leuprolide Acetate Lyophilisate for suspension for injection

    Lupron Depot-Ped 15mg Powder for Injection (00300-3330) (TAP Pharmaceuticals Inc, a Takeda Company) (off market)

    Leuprolide Acetate Lyophilisate for suspension for injection

    Lupron Depot 3-Month 22.5mg Powder for Injection (00300-3346) (AbbVie US LLC) (off market)

    Leuprolide Acetate Lyophilisate for suspension for injection

    Lupron Depot 3-Month 22.5mg Powder for Injection (00300-3346) (TAP Pharmaceuticals Inc, a Takeda Company) (off market)Lupron Depot 3-Month 22.5mg Powder for Injection package photo

    Leuprolide Acetate Lyophilisate for suspension for injection

    Lupron Depot 3-Month 22.5mg Powder for Injection (00300-3338) (TAP Pharmaceuticals Inc, a Takeda Company) (off market)

    Leuprolide Acetate Lyophilisate for suspension for injection

    Lupron Depot 4-Month 30mg Powder for Injection (00300-3683) (AbbVie US LLC) (off market)

    Leuprolide Acetate Lyophilisate for suspension for injection

    Lupron Depot 4-Month 30mg Powder for Injection (00300-3680) (TAP Pharmaceuticals Inc, a Takeda Company) (off market)

    Leuprolide Acetate Lyophilisate for suspension for injection

    Lupron Depot 4-Month 30mg Powder for Injection (00300-3683) (TAP Pharmaceuticals Inc, a Takeda Company) (off market)Lupron Depot 4-Month 30mg Powder for Injection package photo

    Leuprolide Acetate Lyophilisate for suspension for injection [Endometriosis]

    Lupron Depot 1-Month 3.75mg Powder for Injection (00074-3641) (AbbVie US LLC) nullLupron Depot 1-Month 3.75mg Powder for Injection package photo

    Leuprolide Acetate Lyophilisate for suspension for injection [Endometriosis]

    Lupron Depot 3-Month 11.25mg Powder for Injection (00074-3663) (AbbVie US LLC) nullLupron Depot 3-Month 11.25mg Powder for Injection package photo

    Leuprolide Acetate Lyophilisate for suspension for injection [Precocious Puberty]

    Lupron Depot-Ped 7.5mg Powder for Injection (00074-2108) (AbbVie US LLC) nullLupron Depot-Ped 7.5mg Powder for Injection package photo

    Leuprolide Acetate Lyophilisate for suspension for injection [Precocious Puberty]

    Lupron Depot-Ped 11.25mg Powder for Injection (00074-2282) (AbbVie US LLC) nullLupron Depot-Ped 11.25mg Powder for Injection package photo

    Leuprolide Acetate Lyophilisate for suspension for injection [Precocious Puberty]

    Lupron Depot-Ped 3-Month 11.25mg Powder for Injection (00074-3779) (AbbVie US LLC) null

    Leuprolide Acetate Lyophilisate for suspension for injection [Precocious Puberty]

    Lupron Depot-Ped 15mg Powder for Injection (00074-2440) (AbbVie US LLC) null

    Leuprolide Acetate Lyophilisate for suspension for injection [Precocious Puberty]

    Lupron Depot-Ped 3-Month 30mg Powder for Injection (00074-9694) (AbbVie US LLC) nullLupron Depot-Ped 3-Month 30mg Powder for Injection package photo

    Leuprolide Acetate Lyophilisate for suspension for injection [Precocious Puberty]

    Lupron Depot-Ped 6-Month 45mg Powder for Injection (00074-3575) (AbbVie US LLC) nullLupron Depot-Ped 6-Month 45mg Powder for Injection package photo

    Leuprolide Acetate Lyophilisate for suspension for injection [Prostate Cancer]

    Lupron Depot 1-Month 7.5mg Powder for Injection (00074-3642) (AbbVie US LLC) null

    Leuprolide Acetate Lyophilisate for suspension for injection [Prostate Cancer]

    Leuprolide Acetate Depot 3-Month 22.5mg Powder for Injection (69097-0909) (Cipla USA, Inc) nullLeuprolide Acetate Depot 3-Month 22.5mg Powder for Injection package photo

    Leuprolide Acetate Lyophilisate for suspension for injection [Prostate Cancer]

    Lupron Depot 3-Month 22.5mg Powder for Injection (00074-3346) (AbbVie US LLC) null

    Leuprolide Acetate Lyophilisate for suspension for injection [Prostate Cancer]

    Lupron Depot 4-Month 30mg Powder for Injection (00074-3683) (AbbVie US LLC) null

    Leuprolide Acetate Lyophilisate for suspension for injection [Prostate Cancer]

    Lupron Depot 6-Month 45mg Powder for Injection (00074-3473) (AbbVie US LLC) null

    Leuprolide Acetate Solution for injection

    Leuprolide Acetate 14mg/2.8mL Solution for Injection Kit (70121-2537) (Amneal Biosciences) null

    Leuprolide Acetate Solution for injection

    Leuprolide Acetate 14mg/2.8mL Solution for Injection Kit (16714-0572) (NorthStar Rx LLC) null

    Leuprolide Acetate Solution for injection

    Leuprolide Acetate 14mg/2.8mL Solution for Injection Kit (72603-0344) (NorthStar Rx LLC) null

    Leuprolide Acetate Solution for injection

    Leuprolide Acetate 14mg/2.8mL Solution for Injection Kit (00781-4003) (Sandoz Inc. a Novartis Company) null

    Leuprolide Acetate Solution for injection

    Leuprolide Acetate 1mg/0.2ml Solution for Injection (49884-0368) (Par Pharmaceuticals, an Endo Company) (off market)

    Leuprolide Acetate Solution for injection

    Leuprolide Acetate 1mg/0.2ml Solution for Injection (00185-7400) (Sandoz Inc. a Novartis Company) (off market)

    Leuprolide Acetate Solution for injection

    Leuprolide Acetate 1mg/0.2ml Solution for Injection (41616-0936) (Sun Pharmaceutical Industries, Inc.) (off market)

    Leuprolide Acetate Solution for injection

    Leuprolide Acetate 1mg/0.2ml Solution for Injection (00703-4014) (Teva Pharmaceuticals USA) (off market)Leuprolide Acetate 1mg/0.2ml Solution for Injection package photo

    Leuprolide Acetate Solution for injection

    Leuprolide Acetate 1mg/0.2ml Solution for Injection (00703-4024) (Teva Pharmaceuticals USA) (off market)

    Leuprolide Acetate Solution for injection

    Leuprolide Acetate 1mg/0.2mL Solution for Injection (55150-0478) (Eugia US LLC fka AuroMedics Pharma LLC) null

    Leuprolide Acetate Solution for injection

    Leuprolide Acetate 1mg/0.2mL Solution for Injection (47335-0936) (Sun Pharmaceutical Industries, Inc.) null

    Leuprolide Acetate Solution for injection

    Leuprolide Acetate 1mg/0.2mL Solution for Injection (72664-0611) (VGYAAN Pharmaceuticals LLC) nullLeuprolide Acetate 1mg/0.2mL Solution for Injection package photo

    Leuprolide Acetate Solution for injection

    Lupron 5mg/ml Solution for Injection (00300-3612) (AbbVie US LLC) (off market)

    Leuprolide Acetate Solution for injection

    Lupron 5mg/ml Solution for Injection (00300-3612) (TAP Pharmaceuticals Inc, a Takeda Company) (off market)Lupron 5mg/ml Solution for Injection package photo

    Leuprolide Acetate Suspension for injection

    Eligard 7.5mg Suspension for Injection (00024-0793) (Sanofi U.S. LLC) (off market)

    Leuprolide Acetate Suspension for injection

    Eligard 7.5mg Suspension for Injection (00024-0793) (Tolmar Inc.) (off market)

    Leuprolide Acetate Suspension for injection

    Eligard 7.5mg Suspension for Injection (62935-0752) (Tolmar Inc.) (off market)

    Leuprolide Acetate Suspension for injection

    Eligard 22.5mg Suspension for Injection (00024-0222) (Sanofi U.S. LLC) (off market)Eligard 22.5mg Suspension for Injection package photo

    Leuprolide Acetate Suspension for injection

    Eligard 22.5mg Suspension for Injection (00024-0222) (Tolmar Inc.) (off market)

    Leuprolide Acetate Suspension for injection

    Eligard 22.5mg Suspension for Injection (62935-0222) (Tolmar Inc.) (off market)

    Leuprolide Acetate Suspension for injection

    Eligard 30mg Suspension for Injection (00024-0610) (Sanofi U.S. LLC) (off market)Eligard 30mg Suspension for Injection package photo

    Leuprolide Acetate Suspension for injection

    Eligard 30mg Suspension for Injection (00024-0610) (Tolmar Inc.) (off market)

    Leuprolide Acetate Suspension for injection

    Eligard 30mg Suspension for Injection (62935-0302) (Tolmar Inc.) (off market)

    Leuprolide Acetate Suspension for injection

    Eligard 45mg Suspension for Injection (00024-0605) (Sanofi U.S. LLC) (off market)

    Leuprolide Acetate Suspension for injection

    Eligard 45mg Suspension for Injection (00024-0605) (Tolmar Inc.) (off market)

    Leuprolide Acetate Suspension for injection

    Eligard 45mg Suspension for Injection (62935-0452) (Tolmar Inc.) (off market)

    Leuprolide Acetate Suspension for injection [Precocious Puberty]

    Fensolvi 45mg Suspension for Injection (62935-0153) (Tolmar Inc.) null

    Leuprolide Acetate Suspension for injection [Precocious Puberty]

    Fensolvi 45mg Suspension for Injection (62935-0163) (Tolmar Inc.) null

    Leuprolide Acetate Suspension for injection [Prostate Cancer]

    Eligard 7.5mg Suspension for Injection (62935-0753) (Tolmar Inc.) null

    Leuprolide Acetate Suspension for injection [Prostate Cancer]

    Eligard 7.5mg Suspension for Injection (62935-0756) (Tolmar Inc.) null

    Leuprolide Acetate Suspension for injection [Prostate Cancer]

    Eligard 22.5mg Suspension for Injection (62935-0223) (Tolmar Inc.) null

    Leuprolide Acetate Suspension for injection [Prostate Cancer]

    Eligard 22.5mg Suspension for Injection (62935-0227) (Tolmar Inc.) nullEligard 22.5mg Suspension for Injection package photo

    Leuprolide Acetate Suspension for injection [Prostate Cancer]

    Eligard 30mg Suspension for Injection (62935-0303) (Tolmar Inc.) null

    Leuprolide Acetate Suspension for injection [Prostate Cancer]

    Eligard 30mg Suspension for Injection (62935-0306) (Tolmar Inc.) nullEligard 30mg Suspension for Injection package photo

    Leuprolide Acetate Suspension for injection [Prostate Cancer]

    Eligard 45mg Suspension for Injection (62935-0453) (Tolmar Inc.) null

    Leuprolide Acetate Suspension for injection [Prostate Cancer]

    Eligard 45mg Suspension for Injection (62935-0461) (Tolmar Inc.) null

    Leuprolide Mesylate Emulsion for injection

    CAMCEVI 42mg Emulsion for Injection Kit (69448-0014) (Accord BioPharma a division of Accord Healthcare, Inc.) null

    Description/Classification

    Description

    Leuprolide is a synthetic nonapeptide analog of naturally occurring gonadotropin-releasing hormone (GnRH); this analog has greater potency than the natural hormone. It is indicated for the treatment of advanced prostate cancer, central precocious puberty (CPP), and for the management of endometriosis and fibroids.[66709][45097][66721][43800][65368][41676][42683][51299][68727] In men with prostate cancer, a transient tumor flare reaction consisting of worsening bone pain, ureteral obstruction, spinal cord compression, or additional signs and symptoms of prostate cancer may develop during the first few weeks of treatment; closely monitor patients and manage symptoms.[66709][45097][66721][43800][68727] An increase in signs and symptoms of puberty (including vaginal bleeding) may occur during the first weeks of therapy for CPP; instruct patients to notify the health care provider if symptoms continue beyond the second month.[65368][41676]

    Classifications

    • Antineoplastic and Immunomodulating Agents
      • Cytostatic Hormone Therapy
        • Cytostatic Hormone Agonists
          • Cytostatic Gonadotropin-Releasing Hormone Agonists
    • Systemic Hormonal Agents (excluding Sex Hormones)
      • Pituitary and Hypothalamic Hormones
        • Hypothalamic Hormones
          • Gonadotropin-Releasing Hormone Agonists
    Revision Date: 04/07/2024, 02:01:29 PM

    References

    41676 - Lupron Depot-Ped (leuprolide acetate for depot suspension) package insert. North Chicago, IL: Abbott Laboratories; 2023 April.42683 - Lupron Depot-3 month 11.25 mg (leuprolide acetate injection, powder, lyophilized, for suspension) package insert. Osaka, Japan: Takeda Pharmaceutical Company Limited; 2019 March.43800 - Lupron Depot (leuprolide acetate for depot suspension) package insert. North Chicago, IL: AbbVie Inc; 2024 March.45097 - Eligard (leuprolide acetate) package insert. Fort Collins, CO: Tolmar, Inc.; 2024 Jan.51299 - Lupron Depot 1 month 3.75 mg (leuprolide acetate) suspension package insert. Osaka, Japan: Takeda Pharmaceutical Company Limited; 2021 Jan.65368 - Leuprolide acetate (Fensolvi) package insert. Fort Collins, CO: Tolmar, Inc.; 2022 April.66709 - Camcevi (leuprolide) injectable emulsion, for subcutaneous use package insert. Taiwan: Foresee Pharmaceuticals Co., Ltd.; 2024 March.66721 - Lupron (leuprolide acetate for injection) package insert. North Chicago, IL: AbbVie Inc; 2018 Dec.68727 - Lutrate Depot (leuprolide acetate for depot suspension) package insert. Warren, NJ: Cipla USA, Inc.; 2023 Feb.

    Administration Information

    General Administration Information

    For storage information, see the specific product information within the How Supplied section.

    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.

    Hazardous Drugs Classification

    • NIOSH 2016 List: Group 1 [63664]
    • NIOSH (Draft) 2020 List: Table 2
    • Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
    • Use double chemotherapy gloves and a protective gown. Prepare in a biological safety cabinet or compounding aseptic containment isolator with a closed system drug transfer device. Eye/face and respiratory protection may be needed during preparation and administration.[63664]

    Route-Specific Administration

    Injectable Administration

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

    Intramuscular Administration

    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. Do not use partial syringes or a combination of syringes to achieve a particular dose.

     

    Leuprolide acetate for depot suspension

    Preparation (LUPRON Depot and Lupron Depot-Ped)

    • Visually inspect the powder; do not use 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.
    • Use ONLY 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 slowly pushing the plunger for 6 to 8 seconds, until the first stopper is at the blue line in the middle of the barrel.
    • Keeping the syringe upright, mix the powder thoroughly by shaking the syringe 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.
    • Keeping the syringe upright, advance the plunger to expel air from the syringe.
    • 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.[41676][43800]

    Preparation (LUTRATE Depot)

    • Visually inspect the powder; do not use 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.
    • Use ONLY the diluent provided by the manufacturer.
    • After removing the flip top from the vial, place the vial in an upright position.
    • Insert the backstop to the flange of the syringe until you feel it snap in place.
    • Peel away the cover from the blister pack containing the vial adaptor (MIXJECT). Without removing the vial adaptor from the blister pack, place the blister pack with the vial adaptor firmly on top of the vial, piercing it. Push down gently until you feel it snap into place.
    • Remove the cap from the syringe barrel and then remove the blister pack from the vial adaptor.
    • Screw the syringe clockwise into the opening on the side of the vial adaptor to connect them. Gently twist the syringe until it stops turning to ensure a tight connection.
    • While holding the vial, place your thumb on the plunger rod and push it in all the way to transfer the diluent from the pre-filled syringe into the vial. Do not release the plunger rod.
    • Keeping the plunger rod depressed, gently swirl the vial for approximately 1 minute until a uniform milky-white suspension is obtained.
    • Invert the MIXJECT system so that the vial is at the top, and slowly pull back the plunger rod to draw the reconstituted suspension into the syringe.
    • Disconnect the vial adaptor; ONLY grasp the plastic cap of the vial adaptor while disconnecting.
    • Keeping the syringe upright, expel any air from the syringe. Administer immediately to avoid separation of the suspension.[68727]

    IM injection

    • Clean the injection site with an alcohol swab prior to injection.
    • Insert the needle IM at a 90-degree angle into the gluteal area, anterior thigh, or deltoid and look for blood. If present, blood can be seen 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.
    • After injection, withdraw the needle from the injection site.
    • Lupron Depot or Lupron Depot-Ped: 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.
    • Lutrate Depot: Discard the needle in a sharps container.
    • Discard the syringe according to local regulations/procedures.
    • Rotate injection sites within the same region when dose is next due.[41676][42683][43800][51299][68727]

    Subcutaneous Administration

    • Inject appropriate dose subcutaneously. Choose an injection site with sufficient soft or loose subcutaneous tissue (e.g., upper or middle abdominal area, upper buttocks, or other area without excessive pigment, nodules, lesions, or hair); avoid areas with brawny or fibrous subcutaneous tissue or locations that could be rubbed or compressed with a belt or clothing waistband. Periodically rotate the injection site.[45097][65368][66709][66721]

     

    Leuprolide acetate for injection (Lupron)

    Preparation

    • Use the syringes provided by the manufacturer. If it is absolutely necessary to use a different syringe, only a low-dose insulin syringe should be used.
    • After removing the syringe from the outer wrapping, pull the plunger back until the tip is at the 0.2 mL or 20 unit mark.
    • Remove the cover from the needle and push the needle through the rubber stopper. Push the plunger all the way in to inject air into the bottle.
    • Turn the bottle upside down, making sure the tip of the needle is in the liquid. Slowly pull back on the plunger until the syringe fills to the 0.2 mL or 20 unit mark.
    • With the needle still in the bottle and the bottle upside down, check for air bubbles in the syringe. Slowly push any air bubbles back into the bottle and pull the plunger back again to fill to the 0.2 mL or 20 unit mark.

    Subcutaneous injection

    • Cleanse the injection spot with alcohol. Hold the skin taut, or pull up a little flesh with the hand not holding the syringe.
    • Hold the syringe as you would a pencil and thrust the needle into the skin at a 90-degree angle. Push the plunger to administer the injection.
    • Hold an alcohol wipe on your skin where the needle is inserted and withdraw the needle at the same angle it was inserted. Properly dispose of the syringe.[66721]

     

    Leuprolide acetate for injectable suspension (Eligard)

    Preparation

    • Allow the product to reach room temperature before mixing. Once mixed, the product must be administered within 30 minutes.
    • Remove pre-connected syringe system and safety needle from the tray. NOTE: The two syringes will not be lined up.
    • Grasp the latching button on the coupling device with your finger and thumb and press together until you hear a snapping sound. The two syringes should now be aligned. Do not bend the pre-connected syringe system.
    • Hold the syringes horizontally. Mix the product by pushing the liquid contents of Syringe A into the leuprolide acetate powder in Syringe B. Continue mixing by pushing the contents back and forth between both syringes for 60 cycles to obtain a uniformed suspension. One cycle is a push of the Syringe A plunger and a push of Syringe B plunger. When thoroughly mixed, the suspension will appear a light tan to tan color or colorless to pale yellow. NOTE: The product must be mixed as described; shaking the product will not provide adequate mixing of the product.
    • Hold syringes vertically (upright) with Syringe B (wide syringe) on the bottom. Transfer the entire mixed product into Syringe B by depressing the Syringe A plunger and slightly withdrawing the Syringe B plunger. Ensure plunger of Syringe A is fully pushed down.
    • Hold the coupling device and unscrew Syringe B to disconnect it from the device. Syringe A will remain attached to the coupling device. Small air bubbles will remain in the formulation and this is acceptable. Do not purge air bubbles from Syringe B.
    • Keep Syringe B upright with the open end at the top. Hold back the white plunger on Syringe B to prevent loss of the product and attach the safety needle cartridge. Gently screw clockwise with approximately a three-quarter turn until the needle is secure; do not overtighten, as the hub may become damaged resulting in leakage of the product. The safety sheath may also be damaged if the needle is screwed with too much force.
    • NOTE: If the needle hub appears to be damaged or leaking, do NOT use the product and do NOT replace the damaged needle. Use a new replacement Eligard carton.
    • Remove the safety sheath away from the needle and towards the syringe and pull off the clear needle cartridge cover prior to administration.
    • Administer as a single dose subcutaneously.

    Subcutaneous injection

    • Leuprolide acetate (Eligard) must be administered by a healthcare provider.
    • Cleanse the injection spot with alcohol. Grab and bunch the area of skin around the injection site.
    • Using your dominant hand, insert the needle into the skin quickly at a 90-degree angle, then release the skin. Inject the drug using a slow, steady push until the syringe is empty. Withdraw the needle at the same angle it was inserted.
    • If using a safety needle, activate the safety shield immediately following withdrawal by using a thumb, finger, or flat surface to push it forward until it completely covers the needle tip and locks into place; there will be an audible and tactile "click".
    • Properly dispose of the syringe.[45097]

     

    Leuprolide acetate for injectable suspension (Fensolvi)

    Preparation

    • 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 2 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 pale yellow. 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 (wide syringe) by depressing the Syringe A plunger and slightly withdrawing the Syringe B plunger. Uncouple Syringe A while continuing to withdraw the Syringe B plunger. Small air bubbles will remain in the formulation and this is acceptable.
    • Hold Syringe B upright. Hold back the white plunger on Syringe B to prevent loss of the product. Attach the needle cartridge to the end of Syringe B.
    • Remove the clear needle cover prior to administration. Administer as a single dose subcutaneously.

    Subcutaneous injection

    • Leuprolide acetate (Fensolvi) must be administered to a healthcare provider.
    • Cleanse the injection spot with alcohol. Grab and bunch the area of skin around the injection site.
    • Using your dominant hand, insert the needle quickly at a 90-degree angle to the skin surface. After the needle is inserted, release the skin. Inject the drug using a slow, steady push until the syringe is empty. Withdraw the needle at the same angle it was inserted.
    • Activate the safety shield immediately following withdrawal by using a thumb, finger, or flat surface to push it forward until it completely covers the needle tip and locks into place; there will be an audible and tactile "click".
    • Properly dispose of the syringe.[65368]

     

    Leuprolide mesylate injectable emulsion (Camcevi)

    Preparation

    • Remove kit from the refrigerator. Keep the contents in the sealed blister carton and allow it to sit at room temperature for 30 minutes prior to administration. If not used within 30 minutes, return kit to the refrigerator.
    • Remove the prefilled syringe and safety needle from the blister carton. Remove the gray cap from the syringe. Gently attach the needle to the end of the syringe with approximately a three-quarter turn clockwise. Do not overtighten as this may damage the needle hub, causing leakage; the safety sheath could also be damaged.

    Subcutaneous injection

    • Leuprolide mesylate (Camcevi) must be administered to a healthcare provider.
    • Move the safety sheath away from the needle and towards the syringe. Remove the clear needle cover immediately before injection. If the needle hub appears damaged or leaks, do not replace the needle and do not use the product. Use a replacement Camcevi kit.
    • Grab and bunch the skin around the injection site with one hand. Insert the needle at a 90-degree angle to the skin surface, and then release the bunched skin.
    • Inject the full contents of the syringe with a slow and steady push on the plunger, then withdraw the needle at the same 90-degree angle used for insertion.
    • Do not apply heat directly to the site of injection.
    • Immediately after withdrawing the needle, activate the safety sheath using a finger/thumb or flat surface and push until it completely covers the needle tip and locks into place; there will be an audible and tactile "click" that verifies locked position. Properly dispose of the used syringe with the needle protected.[66709]

    Clinical Pharmaceutics Information

    From Trissel's 2‚Ñ¢ Clinical Pharmaceutics Database
      Revision Date: 04/07/2024, 02:01:29 PM

      References

      41676 - Lupron Depot-Ped (leuprolide acetate for depot suspension) package insert. North Chicago, IL: Abbott Laboratories; 2023 April.42683 - Lupron Depot-3 month 11.25 mg (leuprolide acetate injection, powder, lyophilized, for suspension) package insert. Osaka, Japan: Takeda Pharmaceutical Company Limited; 2019 March.43800 - Lupron Depot (leuprolide acetate for depot suspension) package insert. North Chicago, IL: AbbVie Inc; 2024 March.45097 - Eligard (leuprolide acetate) package insert. Fort Collins, CO: Tolmar, Inc.; 2024 Jan.51299 - Lupron Depot 1 month 3.75 mg (leuprolide acetate) suspension package insert. Osaka, Japan: Takeda Pharmaceutical Company Limited; 2021 Jan.63664 - CDC National Institute for Occupational Safety and Health (NIOSH). NIOSH List of Antineoplastic and Other Hazardous Drugs in Healthcare Settings 2016. DHHS (NIOSH) Publication Number 2016-161, September 2016. Available on the World Wide Web at https://www.cdc.gov/niosh/docs/2016-161/pdfs/2016-161.pdf?id=10.26616/NIOSHPUB201616165368 - Leuprolide acetate (Fensolvi) package insert. Fort Collins, CO: Tolmar, Inc.; 2022 April.66709 - Camcevi (leuprolide) injectable emulsion, for subcutaneous use package insert. Taiwan: Foresee Pharmaceuticals Co., Ltd.; 2024 March.66721 - Lupron (leuprolide acetate for injection) package insert. North Chicago, IL: AbbVie Inc; 2018 Dec.68727 - Lutrate Depot (leuprolide acetate for depot suspension) package insert. Warren, NJ: Cipla USA, Inc.; 2023 Feb.

      Adverse Reactions

      Mild

      • abdominal pain
      • acneiform rash
      • agitation
      • alopecia
      • amenorrhea
      • anemia
      • anorexia
      • anxiety
      • appetite stimulation
      • arthralgia
      • asthenia
      • back pain
      • breast enlargement
      • chills
      • cough
      • diarrhea
      • dizziness
      • drug-induced body odor
      • dysgeusia
      • dysmenorrhea
      • dyspepsia
      • ecchymosis
      • emotional lability
      • epistaxis
      • eructation
      • fatigue
      • fever
      • flatulence
      • flushing
      • gingivitis
      • gynecomastia
      • headache
      • hiccups
      • hirsutism
      • hyperhidrosis
      • hyperkeratosis
      • hyperkinesis
      • hyporeflexia
      • increased urinary frequency
      • infection
      • influenza
      • injection site reaction
      • insomnia
      • irritability
      • lethargy
      • libido decrease
      • libido increase
      • malaise
      • mastalgia
      • melasma
      • menstrual irregularity
      • muscle cramps
      • musculoskeletal pain
      • myalgia
      • nasal congestion
      • nausea
      • night sweats
      • nocturia
      • pallor
      • paresthesias
      • parosmia
      • pharyngitis
      • photosensitivity
      • pruritus
      • ptosis
      • purpura
      • rash
      • rhinitis
      • seborrhea
      • sinusitis
      • skin hyperpigmentation
      • skin hypopigmentation
      • syncope
      • testicular pain
      • tinnitus
      • tremor
      • urinary urgency
      • urticaria
      • vaginal discharge
      • vertigo
      • vomiting
      • weakness
      • weight gain
      • weight loss
      • xerophthalmia
      • xerosis
      • xerostomia

      Moderate

      • amblyopia
      • amnesia
      • angina
      • bladder spasm
      • blurred vision
      • bone pain
      • chest pain (unspecified)
      • colitis
      • confusion
      • conjunctivitis
      • constipation
      • cystitis
      • dehydration
      • depression
      • diabetes mellitus
      • dysphagia
      • dysphonia
      • dyspnea
      • dysuria
      • edema
      • elevated hepatic enzymes
      • eosinophilia
      • erythema
      • euphoria
      • galactorrhea
      • goiter
      • growth inhibition
      • hallucinations
      • hematoma
      • hematuria
      • hemoptysis
      • hepatitis
      • hepatomegaly
      • hot flashes
      • hypercalcemia
      • hypercholesterolemia
      • hyperesthesia
      • hyperglycemia
      • hyperlipidemia
      • hyperphosphatemia
      • hyperreflexia
      • hypertension
      • hypertriglyceridemia
      • hyperuricemia
      • hypoalbuminemia
      • hypokalemia
      • hypotension
      • hypoxia
      • impaired wound healing
      • impotence (erectile dysfunction)
      • interstitial lung disease
      • leukopenia
      • lymphadenopathy
      • memory impairment
      • myopathy
      • nephrolithiasis
      • osteopenia
      • osteoporosis
      • ovarian enlargement
      • palpitations
      • peripheral edema
      • peripheral neuropathy
      • phlebitis
      • prolonged bleeding time
      • prostate pain
      • pseudotumor cerebri
      • pyuria
      • QT prolongation
      • sinus tachycardia
      • skin ulcer
      • synovitis
      • testicular atrophy
      • thrombocytopenia
      • tumor flare
      • urinary incontinence
      • urinary retention
      • urinary tract obstruction
      • vaginal bleeding
      • vaginitis
      • wheezing

      Severe

      • acute generalized exanthematous pustulosis (AGEP)
      • anaphylactoid reactions
      • anemia
      • atrial fibrillation
      • bone fractures
      • bradycardia
      • bronchospasm
      • dementia
      • Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)
      • epididymitis
      • erythema multiforme
      • feminization
      • GI bleeding
      • GI obstruction
      • hearing loss
      • heart failure
      • hepatotoxicity
      • muscle paralysis
      • myocardial infarction
      • new primary malignancy
      • ovarian hyperstimulation syndrome
      • peptic ulcer
      • pituitary apoplexy
      • pleural effusion
      • pulmonary edema
      • pulmonary embolism
      • pulmonary fibrosis
      • rectal fistula
      • renal tubular obstruction
      • seizures
      • spinal cord compression
      • Stevens-Johnson syndrome
      • stroke
      • suicidal ideation
      • thromboembolism
      • thrombosis
      • toxic epidermal necrolysis
      • visual impairment

      Leuprolide may cause adverse effects related to decreased testosterone and estrogen. In males, serum testosterone is reduced to castrate concentrations (less than 50 ng/dL). In premenopausal females, circulating estrogens are reduced to postmenopausal concentrations. After leuprolide initiation, these decreases in hormonal concentrations occur within 2 to 4 weeks. Leuprolide may be used therapeutically to induce a hypo-estrogenic, menopause-like condition in females, which is an induced amenorrhea that usually occurs within 3 months of initiating depot therapy; in some female patients, such a result might be considered a side effect of the drug (74% to 98%). Women treated with leuprolide also reported vaginitis (11% to 28%) and unspecified menstrual disorders (2% to 5%).[42683] [51299] Hot flashes occurred in 25% to 98% of men with prostate cancer who received leuprolide; in a small study (n = 74), hot flashes were less common in men who had been orchiectomized (8.3%). Hot flashes also occurred in 73% to 98% of women with endometriosis or fibroids treated with leuprolide; 5% of pediatric patients treated with leuprolide reported hot flushes in 1 trial, 2% reported vasodilation in another, and flushing was reported in postmarketing experience. Gynecomastia occurred in 7.1% or less of men with prostate cancer who received leuprolide; breast enlargement was reported separately in less than 5% of men as well as in postmarketing reports of pediatric patients treated with leuprolide. Less than 2% of pediatric patients reported gynecomastia/breast disorders. Breast soreness or tenderness (mastalgia) occurred in 7% or fewer men, 6% of women with endometriosis, and 4% of children who received leuprolide. Lactation occurred in less than 5% of women in 1 study.[66721] [43800] [41676] [42683] [51299] [45097] [66709] [65368] [68727] Additional adverse reactions in men with prostate cancer related to reduced testosterone include testicular pain (less than 5%), testicular atrophy or decreased testicular size (20.2% or less), impotence (erectile dysfunction) (5.4% or less), hyperhidrosis or sweating (2% or less), clamminess (4.4% or less), night sweats (3.3% or less), penis disorder (less than 5%), reduced penis size (less than 2%), and testis disorder (less than 5%). Prostate pain was reported in postmarketing experience with men receiving leuprolide for the treatment of prostate cancer. Libido decrease (5.4% or less) or loss of libido (less than 2%) was reported in men treated with leuprolide; additionally, 10% to 11% of women receiving treatment for fibroids reported decreased libido.[66721] [43800] [45097] [66709] [68727] In pediatric patients, accelerated sexual maturity, dysmenorrhea, feminization, growth inhibition, hirsutism, and unspecified menstrual disorders each occurred in less than 2% of patients; hyperhidrosis was reported in 4% of patients.[65368] [41676]

      Administration of leuprolide results in an initial increase in circulating concentrations of luteinizing hormone and follicle stimulating hormone, which leads to a transient increase in concentrations of testosterone (to approximately 50% above baseline) and dihydrotestosterone in males during the first 2 weeks of treatment; testosterone concentrations typically decline to baseline or below by the end of the second week of treatment and to castrate levels within 2 to 4 weeks after starting treatment. Patients with prostate cancer may experience worsening of symptoms or onset of new symptoms (tumor flare). Cases of urinary tract obstruction and spinal cord compression, which may contribute to muscle paralysis with or without fatal complications, have been reported with LHRH agonists such as leuprolide. Monitor patients for symptoms of tumor flare during the first few weeks of treatment; closely monitor patients with urinary tract obstruction or metastatic vertebral lesions for new or worsening symptoms. If spinal cord compression or renal impairment develops, institute standard treatment of these complications. This transient increase in testosterone concentrations is usually manifested by an increase in bone pain (7% or less), but may also include neuropathy, hematuria (6.1% or less), or renal tubular obstruction/bladder outlet obstruction (less than 5%); temporary weakness (3.6% or less) and lower limb paresthesia have been reported in a few cases. Additional possible testosterone-related adverse events reported with leuprolide treatment in men with prostate cancer include increased prostatic acid phosphatase (5% or more), balanitis (less than 5%), epididymitis (less than 5%), prostate disorder (less than 5%), testicular soreness/pain (less than 2%), libido increase, and penile swelling; decreased prostatic acid phosphatase occurred in at least 5% of men in 1 study. Spinal fracture/paralysis was reported in postmarketing experience with leuprolide in prostate cancer patients. Aggravation of a preexisting tumor occurred in less than 2% of pediatric patients who received leuprolide.[41676] [45097] [66709] [43800] [66721] [68727]

      Unspecified urinary disorders occurred in 10.2% to 16.5% of men with prostate cancer treated with leuprolide in 2 clinical trials. Specific urinary and related laboratory adverse events occurring in men with prostate cancer in various clinical trials include urinary retention (less than 2%), nocturia (9% or less), increased urinary frequency (2.2% to 12%), urinary urgency (less than 2%), frequency/urgency (6.1% or less), dysuria (less than 5%), micturition urgency which included dysuria (6% or less), urinary incontinence (less than 5%), urination difficulty (less than 2%), urination pain (8% or less), scanty urination (less than 2%), bladder spasm (less than 5%), increased or decreased urine specific gravity (5% or more), dehydration (8.2% or less), post void residual, pyuria, and uric aciduria (5% or more).[45097] [66709] [66721] [43800] [68727] Dysuria was also reported in less than 5% of women receiving leuprolide for the treatment of endometriosis, as a possible effect related to decreased estrogen concentrations; renal calculus (nephrolithiasis) occurred in 0.7% of these women. Urinary incontinence occurred in less than 5% of women treated with leuprolide for fibroids and in less than 2% of pediatric patients receiving leuprolide.[42683] [51299] [41676]

      Emotional lability or mood swings, and depression have been reported with leuprolide treatment. There have been very rare reports of suicidal ideation and attempt. Many, but not all, of these patients had a history of depression or other psychiatric illness. Patients should be counseled on the possibility of development or worsening of depression during treatment with leuprolide. Monitor patients for worsening of psychiatric symptoms during treatment with leuprolide. Refer patients with new or worsening depression to a mental health professional, as appropriate.[43800] [41676] [65368] [42683] [51299] Depression and mood swings each occurred in less than 5% of men with prostate cancer treated with leuprolide; suicidal ideation and attempt was reported in postmarketing experience.[45097] [66721] [43800] [66709] [68727]. Depression and/or emotional lability was reported in 11% to 31% of women with endometriosis or fibroids treated with leuprolide, and is thought to be a possible effect of decreased estrogen in these patients; serious cases of depression were reported in 0.7% of patients, and both mood swings and suicidal ideation/attempt were reported in postmarketing experience.[42683] [51299] Psychiatric events, including affect lability, affective disorder, aggression, crying, depressed mood, disruptive mood dysregulation disorder, auditory hallucination, altered mood, mood swings, and trichotillomania were reported in 22% of pediatric patients with central precocious puberty (CPP) receiving leuprolide every 6 months. Altered mood occurred in 5% and depression in less than 2% of pediatric patients with CPP treated with leuprolide, while emotional lability (5%), a general emotional disorder (2%), crying, and tearfulness were also reported in this patient population.[41676] [65368] Additional psychiatric effects that occurred in women and were thought to be a possible effect of deceased estrogen included insomnia (31% or less) and anxiety/nervousness (8% or less).[42683] [51299] Anxiety and nervousness were also reported in less than 5% of men with prostate cancer who received leuprolide, and in less than 2% of children with CPP. Insomnia was reported in 8.5% or fewer men with prostate cancer treated with leuprolide, and was reported in 4% of children.[45097] [66709] [66721] [41676] [65368] [43800] Amnesia (6% or fewer) and delusions (less than 5%) were reported in both men and women treated with leuprolide; unspecified memory disorders (memory impairment) were separately reported in less than 5% of men who received leuprolide.[66721] [43800] [42683] [51299] Abnormal thinking, agitation, auditory hallucinations/tinnitus, confusion, dementia, euphoria, and were each reported in less than 5% of men treated with leuprolide.[66721] [43800] Irritability was reported in 2% of leuprolide-treated children, and unspecified personality disorder in less than 5% of treated women.[65368] [42683] [51299]

      Nausea/vomiting occurred in 5% to 25% of women with endometriosis or fibroids treated with leuprolide; it was less commonly reported in men with prostate cancer (9% or less). In children with central precocious puberty (CPP), less than 2% of patients experienced nausea and/or vomiting with monthly leuprolide administration compared to 13% with leuprolide administration every 6 months.[45097] [66721] [65368] [41676] [42683] [51299] [68727] Altered bowel function was reported in 14% of women treated with leuprolide.[42683] [51299] Diarrhea was reported in 13% or fewer men with prostate cancer and in 16% of children with CPP receiving leuprolide every 6 months. Constipation was reported by 9% or fewer men and children who received leuprolide.[66721] [45097] [43800] [65368] [41676] [68727] Unspecified GI disturbances were reported in 7% or fewer patients treated with leuprolide. Changes in appetite were reported in 13% or less of treated women, while anorexia occurred in 6% or fewer men and appetite stimulation was reported in less than 5% of men and less than 2% of children; decreased appetite was reported in postmarketing experience in children with CPP who received leuprolide. Weight gain was reported in up to 7% of children and less than 2% of men treated with leuprolide, and was reported in 12% of women; conversely, weight loss occurred in less than 5% of men who received leuprolide.[42683] [51299] [66721] [43800] [65368] [41676] Additional gastrointestinal adverse reactions reported in men and children treated with leuprolide include dyspepsia (less than 2%), dysphagia (less than 5%), and gingivitis (less than 5%).[45097] [66721] [43800] [41676] Xerostomia and thirst occurred in less than 5% of men and women treated with leuprolide.[42683] [51299] [66721] [43800] Adverse reactions only reported in men with prostate cancer who received leuprolide include gum hemorrhage (less than 5%), periodontal abscess (less than 5%), duodenal ulcer (less than 5%), peptic ulcer (less than 5%), abdominal distension (less than 5%), eructation (less than 5%), flatulence (less than 2%), gastroenteritis/colitis (2.5% or less), GI bleeding (less than 5%), occult blood on rectal exam, GI obstruction (less than 5%), rectal fistula/erythema, rectal polyps (less than 5%), and unspecified GI disorders which included dyspepsia and flatulence (0.2% to 16%).[43800] [66721] [45097] Abdominal pain was reported in 8% of men with prostate cancer in 1 study and in up to 18% of children with CPP treated with leuprolide.[65368] [41676] [68727]

      A localized injection site reaction including induration and abscess has been reported with leuprolide administration.[66721] [43800] [42683] [51299] [41676] [65368] Reactions including pain, erythema, hemorrhage, nodule, paresthesia, pruritus, and warmth at the site occurred in 6% to 37.5% of men with prostate cancer treated with Lupron Depot doses 22.5 mg and higher or Camcevi; the incidence was less than 5% in men receiving the 7.5 mg dose of Lupron Depot and in women with endometriosis or fibroids who also received Lupron Depot (3.75 mg or 11.25 mg doses). A general skin reaction and ecchymosis were each reported in 8.5% or fewer men and women treated with leuprolide; in 1 small study, a general skin was reported in 12.2% of nonorchiectomized men who received leuprolide 30 mg and in 0% of orchiectomized men.[66721] [43800] [66709] [42683] [51299] [68727] Out of 1,338 Eligard injections administered to men with prostate cancer, injection site reactions included mostly brief and mild burning/stinging (16% to 34.6%), pain (2.3% to 4.6%), erythema (0.9% to 2.6%), and bruising (1.7% to 2.5%); pruritus (0.4% to 2.6%), induration (0.4%), and skin ulcer (0.1%) were also reported.[45097] Injection site reactions, including injection site pain, erythema, warmth, bruising, discomfort, and swelling, were reported in 78% of pediatric patients receiving leuprolide every 6 months for central precocious puberty. Mostly mild to moderate injection site reactions including abscess were reported in 9% of pediatric patients receiving leuprolide every month, while injection site pain (19% to 21%) and swelling (2%) were reported in patients receiving leuprolide every 3 months. Sterile abscess, hematoma, induration, and warmth at the injection site were listed as less common injection site reactions. Pruritus (11%) was also reported in this population.[65368] [41676]

      Symptoms consistent with anaphylactoid reactions have rarely been reported (0.002%) with leuprolide treatment; anaphylactic reactions to Gonadotropin Releasing Hormone (GnRH) agonists have been reported in the medical literature. General reports of allergic reaction have been reported with leuprolide during clinical trials (estimated incidence less than 2%). Allergic reactions have included rash (less than 2%), urticaria, and photosensitivity reactions.[41676] [42683] [43800] [45097] [51299] [66709] [66721] [65368] Rash, including erythema multiforme, occurred in 3% of pediatric patients treated with leuprolide monthly and in 7% of patients receiving leuprolide every 6 months. Androgen-like effects of leuprolide in women have included acne (10%) and alopecia (less than 5%). Acneiform rash/seborrhea (3%), alopecia (less than 2%), and hair disorder (less than 2%) were also reported children. Drug-induced body odor and nail disorders were reported in women (less than 5% each) and as less common adverse reactions in children receiving leuprolide.[41676] [42683] [51299] Skin hypopigmentation (leukoderma) and purpura occurred in less than 2% of children; pallor was reported as a less common adverse reaction. Hyperkeratosis and skin hypertrophy were also reported.[41676] Alopecia/hair disorder (less than 5%), cysts (less than 5%), dermatitis (5%), impaired wound healing (less than 5%), melanosis/melasma (less than 5%), skin hyperpigmentation (less than 5%), skin lesions (less than 5%), xerosis (less than 5%), hyperkeratosis, skin hypertrophy, pallor, blisters on penis, hives, moles, pubic boils, and spiders have been reported in men who received leuprolide for prostate cancer; hair growth was reported in postmarketing experience.[45097] [43800] [41676] [66709] [66721] [65368]

      As with other GnRH agonists, there have been reports of ovarian cyst formation (and ovarian enlargement) with the use of leuprolide in females during various types of infertility protocols. When leuprolide is used in combination with gonadotropins, ovarian hyperstimulation syndrome (OHSS) has also occurred.[63289]

      Pituitary apoplexy is a syndrome due to a sudden infarction in the pituitary gland. Rare cases of pituitary apoplexy have been reported after the administration of Gonadotropin Releasing Hormone (GnRH) agonists including leuprolide during postmarketing surveillance. In most cases, a pituitary adenoma was diagnosed. A majority of pituitary apoplexy cases occur within 2 weeks of the first dose and some within the first hour. In these cases, pituitary apoplexy has presented as a sudden and severe headache, nausea/vomiting, visual changes including reduction in visual field and ophthalmoplegia, altered mental status, and sometimes cardiovascular collapse. The presence of acute visual loss (e.g., bitemporal hemianopia or hemianopsia) and ocular paresis (reductions in ocular movements from involvement of cranial nerves III, IV, and VI) can assist in the diagnosis. Immediate medical management may be required; management strategies include close observation, corticosteroid administration, maintenance of fluid and electrolyte balance, and possibly surgical decompression of the pituitary fossa.[31507] [31508] [66709] [45097] [66721] [43800] [65368] [41676] [42683] [51299] [68727]

      Treatment with leuprolide can cause decreased bone mineral density (BMD) which can result in osteopenia and a risk for osteoporosis. In women with endometriosis treated with leuprolide, the mean change in BMD of the lumbar spine from baseline at week 24 (n = 41) was -3.2% and at week 52 (n = 29) was -6.3%; in patients who received leuprolide plus norethindrone, the mean change from baseline at week 24 (n = 42) was -0.3% and at week 52 (n = 32) was -1%. Eight months after discontinuation of therapy, the mean change from baseline in patients treated with leuprolide was -3.3% compared with -0.9% for those who received leuprolide/norethindrone; at 12 months, the mean change from baseline was -2.2% versus -0.7%, respectively. In patients receiving leuprolide for the treatment of uterine fibroids, vertebral trabecular BMD showed a mean decrease of 2.7% from baseline at 3 months; a trend toward recovery was observed 6 months after discontinuation of therapy.[51299] [42683] Reduced BMD has also been reported in published literature and postmarketing in pediatric patients with central precocious puberty treated with leuprolide. Published studies have indicated that after discontinuation of leuprolide therapy in children, subsequent bone mass accrual is preserved and peak bone mass in late adolescence does not seem to be affected.[41676] Long periods of medical castration in men can be anticipated to have effects on bone density. Decreased BMD has been reported in men treated with a Gonadotropin Releasing Hormone (GnRH) or a Luteinising Hormone-Releasing Hormone (LHRH) agonist analog. In a clinical trial, 25 men with prostate cancer, 12 of whom had been treated previously with leuprolide acetate for at least 6 months, underwent BMD studies as a result of pain. The leuprolide-treated group had lower bone density scores than the non-treated control group. Pathological bone fractures were reported in less than 5% of men with prostate cancer treated with leuprolide.[45097] [66721] [43800] [66709] [68727]

      General complaints of pain (4.2% to 32.7%) and joint disorders (8% to 16.3%) were reported in men with prostate cancer and women with endometriosis or fibroids who were treated with leuprolide in clinical trials; joint disorders were considered to be a possible effect of decreased estrogen status in women.[42683] Arthralgia (1.3% to 11%), extremity pain (10% or less), musculoskeletal pain including back pain and bone pain (11% or less), myalgia (8.2% or less) occurred in men who received leuprolide for prostate cancer in clinical trials. Additional musculoskeletal adverse reactions reported in men treated with leuprolide include ankylosing spondylosis, arthritis, back pain (less than 2%), blurred disc margins, disc hernia (less than 5%), inguinal hernia, joint pain (less than 5%), leg cramps (less than 5%), limb pain (2.7% or less), muscle atrophy (less than 2%), muscle stiffness, muscle tenderness, neck pain (less than 5%), pelvic fibrosis, accidental injury, and knee effusion. Muscle cramps/spasms were reported postmarketing.[66709] [66721] [43800] [51299] [68727] Fibromyalgia and tenosynovitis-like symptoms have been reported postmarketing in both men and women.[66709] [66721] [43800] [42683] [51299] General pain (3%), extremity pain (9%), back pain (7%), ligament sprain (7%), fracture, including ankle and tibia fractures (4%), arthralgia (less than 2%), myalgia (less than 2%), and joint disorders (less than 2%) were reported in pediatric patients with central precocious puberty (CPP). Hyperkinesis, myopathy, antinuclear antibody present, and increased sedimentation rate were also reported in less than 2% of pediatric patients who received leuprolide; synovitis and epiphysiolysis have been reported in postmarketing experience.[65368] [41676]

      Hyperglycemia (at least 5% in some studies; less than 5% in others) and an increased risk of developing diabetes mellitus have been reported with the use of Gonadotropin Releasing Hormone (GnRH) agonists in men; diabetes has also been reported in postmarketing experience in pediatric studies with leuprolide. The risk for diabetes in women is unknown due to a lack of data. Periodically monitor blood glucose concentration and/or glycosylated hemoglobin (HbA1c) in those receiving leuprolide therapy. Manage patients according to current clinical practice.[40127] [42683] [66709] [45097] [66721] [43800] [65368] [41676] [68727]

      Leukopenia was noted in at least 5% of men with prostate cancer who received leuprolide; leukopenia occurred in more than 10% of men with prostate cancer who received 1 formulation of leuprolide (Lutrate Depot), while decreased white blood cells (WBC) have also been reported in postmarketing experience with all other populations treated with leuprolide products. Increased WBC and eosinophilia have each occurred in at least 5% of men treated with leuprolide. Decreased red blood cells, hematocrit, and hemoglobin were reported in less than 5% of men who received leuprolide; anemia was reported in 5% or less of these patients and in more than 10% of patients treated with Lutrate Depot. In one study, 13.9% of men had a grade 1 or 2 decreased hemoglobin at baseline; during treatment with Lupron Depot, grade 1 (42.4%), grade 2, (2%), and grade 3 or 4 (1.3%) hemoglobin reductions were reported. Thrombocytopenia and decreased platelets were each reported in at least 5% of men; increased platelets were also reported in at least 5% of patients in this population. Additionally, prolonged bleeding time (increased PT and PTT) occurred in at least 5% of men with prostate cancer treated with leuprolide in one clinical trial.[41676] [42683] [43800] [45097] [51299] [65368] [66709] [66721] [68727]

      Fever/chills was reported in less than 5% of men with prostate cancer treated with leuprolide and fever in 17% or fewer children with central precocious puberty (CPP) treated with leuprolide. General reports of infection or inflammation were reported in 5.4% or fewer men who received leuprolide and was a reported as a less common adverse reaction in patients with CPP.[66721] [43800] [65368] [41676] Urinary tract infection (UTI) occurred in 7% or fewer men treated with leuprolide; in one small study, 6.6% of men reported UTI/cystitis during treatment but was not felt to be related to treatment in any patient. Serious cases of UTI were reported in 1.9% of women with endometriosis who received leuprolide; pyelonephritis was reported in women with fibroids treated with leuprolide 7.5 mg monthly but not in those who received 3.75 mg monthly.[66721] [43800] [42683] [51299] [68727] Upper respiratory infection (URI) was reported in 17% or fewer men with prostate cancer and children with CPP treated with leuprolide in clinical trials; in one trial, URI occurred in 21.2% of men who received leuprolide but was not felt to be related to therapy in any patient.[66709] [43800] [65368] [68727] In all populations treated with leuprolide including women with endometriosis or fibroids, influenza (less than 5%), rhinitis (less than 5%), and sinusitis (less than 5%) were reported.[66721] [43800] [41676] [42683] [51299] Pharyngitis occurred in less than 5% of men while strep throat was also reported; nasopharyngitis occurred in 22% or fewer pediatric patients.[43800] [41676] [65368] Additional infection-related events reported in men who received leuprolide include abscess (less than 5%), bronchitis (less than 5%), cellulitis (less than 5%), lymphadenopathy (less than 5%), pneumonia (less than 5%; serious cases, at least 2%), pulmonary infiltrates, and shingles/herpes zoster (less than 5%).[66721] [43800]

      Respiratory disorders (10.7% or less) reported in men with prostate cancer treated with leuprolide, included: asthma (less than 5%), chest tightness, decreased breath sounds, cough (less than 5%), dysphonia (less than 5%), dyspnea (less than 2%) emphysema (less than 5%), epistaxis (less than 5%), hemoptysis (less than 5%), hiccups (less than 5%), hypoxia (less than 5%), lung disorder (less than 5%), pleuritic chest pain, pleural effusion (less than 5%), pleural rub (less than 5%), pulmonary edema (less than 5%), pulmonary fibrosis (less than 5%), rales/rhonchi, sinus/nasal congestion (5% or less), wheezing (less than 5% and often associated with URI), and increased sputum (less than 5%); interstitial lung disease was reported in postmarketing experience with leuprolide. Cough (13% or less), productive cough (6% or less), bronchospasm (6% or less), and asthma (less than 2%) were also reported in children with central precocious puberty treated with leuprolide, along with epistaxis (less common), and dyspnea (postmarketing). Asthma or wheezing was also reported in leuprolide-treated women with pre-existing histories of asthma or environmental or drug allergies.[42683] [51299] [66721] [43800] [41676] [65368] [68727]

      In men, an increased risk of myocardial infarction, sudden cardiac death, and stroke has been reported in association with the use of Gonadotropin Releasing Hormone (GnRH) agonists; the risk appears to be low based on the reported odds ratios. Carefully evaluate cardiovascular risk factors when determining the treatment plan for men with prostate cancer. Monitor patients for signs and symptoms suggestive of the development of cardiovascular disease; if cardiac disease develops, manage patients according to current clinical practice.[66721] [43800] [45097] [66709] [68727] At this time, there are no known comparable studies evaluating the risk of cardiovascular disease in women or children taking GnRH agonists for other indications.[42122] Leuprolide may cause QT prolongation. Ischemia/ECG changes occurred in up to 19% of men with prostate cancer treated with leuprolide.[66721] [68727] Palpitations and sinus tachycardia were each reported in less than 5% of adults (men and women) treated with leuprolide while myocardial infarction occurred in less than 5% of men and in postmarketing experience with women. Stroke and transient ischemic attack (TIA) were reported in men who received leuprolide and in postmarketing experience with women; serious cases of stroke/TIA occurred in at least 2% of men who received Lupron Depot in one study. Phlebitis/thrombosis occurred in 2% or fewer men who received leuprolide. Deep thrombophlebitis/DVT/thromboembolism and pulmonary embolism each occurred in less than 5% of men and in postmarketing experience with women. Ruptured aortic aneurysm, atrial fibrillation (less than 5%), cardiac arrhythmias (less than 5%), carotid bruit, extrasystole, heart failure (less than 5%), and murmur (3% or less) were also reported in leuprolide-treated men.[66721] [43800] [42683] [51299] Hypertension occurred in 15% of men with prostate cancer treated with leuprolide mesylate (Camcevi), in 8.3% or fewer men receiving leuprolide acetate, in less than 2% of children with central precocious puberty (CPP) who received leuprolide acetate, and in postmarketing experience with women with endometriosis or fibroids treated with leuprolide acetate. Hypotension occurred in less than 5% of men and in postmarketing experience with leuprolide in other populations; syncope was reported in less than 5% of adults and in less than 2% of children treated with leuprolide.[66709] [45097] [66721] [43800] [65368] [41676] [42683] [51299] [68727] Angina related to treatment was reported in less than 5% of leuprolide-treated men while chest pain (unspecified) was reported in 4% of children.[66721] [43800] [65368] [41676] Bradycardia occurred in less than 5% of men and less than 2% of children who received leuprolide; varicose veins were reported in less than 5% of men and peripheral vascular disorder in less than 2% of children.[66721] [43800] [41676]

      Although the relationship to drug treatment is difficult to assess in this population, various laboratory abnormalities were reported in men with prostate cancer treated with leuprolide, including decreased bicarbonate (5% or more), hyperphosphatemia (5% or more), hyperuricemia (5% or more), increased BUN (Lupron Depot, 5% or more; Lupron, less than 5%), increased creatinine (Lupron Depot, 5% or more; Lupron, less than 5%), and increased calcium (hypercalcemia) (less than 5%). Decreased potassium concentrations (hypokalemia) was also reported in clinical trials and postmarketing experience.[43800] [66721]

      During the early phase of therapy, because gonadotropins and sex steroids rise above baseline because of the initial stimulatory effect of the drug, an increase in clinical signs and symptoms of puberty may also be observed in pediatric patients during the first weeks of therapy or after subsequent doses; vaginitis/vaginal bleeding/vaginal discharge occurred in 3% of pediatric patients with central precocious puberty in one study; vaginal bleeding was reported in postmarketing experience with pediatric patients receiving leuprolide.[41676] [65368] In women receiving leuprolide for endometriosis or uterine fibroids, an increase in symptoms may be observed during the initial days of therapy, but these should dissipate with continued therapy. Endocrine adverse effects in women treated with leuprolide have included menstrual irregularity (changes in vaginal bleeding patterns or other menstrual disorders) and lactation (galactorrhea).[42683]

      Seizures occurred in less than 5% of men with prostate cancer treated with leuprolide in one clinical trial and 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. Manage patients receiving leuprolide who experience convulsions according to current clinical practice.[41676] [43800] [51299] [66709] [42683] [65368] [45097] [66721] [68727]Pseudotumor cerebri (idiopathic intracranial hypertension) has been reported in pediatric patients during postmarketing experience.[41676] [65368] Dizziness (including vertigo) was reported in 2% to 8.3% (grade 3 or 4, 0.7% or less) of men with prostate cancer treated with leuprolide; dizziness was also individually reported in 3.3% to 7% and vertigo in less than 2%.[45097] [66709] [66721] [43800] Dizziness and/or vertigo occurred in 11% to 16% of women treated with leuprolide for endometriosis or fibroids, and was reported as a less common adverse reaction in pediatric patients treated for central precocious puberty.[51299] [42683] [41676] Taste perversion or disorders (dysgeusia) were reported in less than 5% of men and women treated with leuprolide.[66721] [51299] [42683] [45097] Additional CNS-related adverse reactions reported in men with prostate cancer included hyperreflexia (less than 5%), hyporeflexia (less than 5%), loss of smell (parosmia, less than 5%), rigors (less than 2%), and tremor (less than 2%).[66721] [45097] Gait disturbance was a less commonly reported adverse reaction in pediatric patients treated with leuprolide.[41676]

      Ocular adverse reactions occurring in less than 5% of men with prostate cancer treated with leuprolide include visual impairment, amblyopia, blurred vision, ptosis, and xerophthalmia; eyelid growth and perivascular cuffing of the eye were also reported in men treated with leuprolide.[43800] [66721] Unspecified ophthalmologic disorders that were possibly an effect of decreased estrogen and conjunctivitis were also reported in less than 5% of women with endometriosis or fibroids treated with leuprolide.[42683] [51299] Decreased vision was a less common adverse reaction reported in pediatric patients with central precocious puberty treated with leuprolide.[41676]

      Paresthesias occurred in 8.2% or fewer men with prostate cancer treated with leuprolide in clinical trials; they also occurred in 7% of women with endometriosis who received lower doses of leuprolide in one study.[66721] [43800] [42683] [51299] Neuromuscular disorders (i.e., leg cramps, paresthesia) were reported in less than 9.6% of men with prostate cancer who received leuprolide and in 2% to 7% of women with endometriosis in 2 studies as a possible effect of decreased estrogen.[43800] [42683] [51299] Additional adverse events reported in men with prostate cancer treated with leuprolide include hyperesthesia (less than 5%), motor deficiency (less than 5%), neuropathy (less than 5%), numbness (less than 5%), peripheral neuropathy (less than 5%), weakness (3.6% or less), and "feet burning".[45097] [66721] [43800] [66709] Peripheral neuropathy also occurred in postmarketing experience with women treated with leuprolide.[42683] [51299]

      Headache (26% to 65%) was commonly reported in women with endometriosis or fibroids treated with leuprolide in clinical trials, possibly as an effect of decreased estrogen; it was less common in men with prostate cancer treated with leuprolide (10.2% or less) and in children with central precocious puberty (CPP) who received leuprolide treatment.[42683] [51299] [66721] [43800] [65368] [41676] [68727] Asthenia (12.2% or less), fatigue (including asthenia) (15% or less), fatigue/malaise (17.5% or less), fatigue/lethargy (11.9% or less), fatigue as a stand-alone term (less than 5%), and lethargy as a stand-alone term (less than 5%) were also reported in men who received leuprolide across clinical trials.[66721] [43800] [66709] [45097] [68727] Asthenia occurred in 8% to 18% of women treated with leuprolide, and was a less commonly reported adverse reaction in children with CPP; somnolence occurred in less than 2% of children with CPP who received leuprolide and fatigue was reported in postmarketing experience.[65368] [41676] [42683] [51299] Decreased hearing/hearing loss and hearing disorders were reported in postmarketing experience in men treated with leuprolide.[66721]

      Elevated hepatic enzymes (2 x baseline and above the upper limit of normal) occurred in 1% to 3% of women with endometriosis or fibroids treated with leuprolide; the increases observed in most (83.3%) of the women with endometriosis occurred beyond 6 months of treatment.[42683] [51299] Increased liver function tests (e.g., ALT, AST, GGTP, LDH) were also reported in at least 5% of men with prostate cancer treated with leuprolide, along with hypoalbuminemia (5% or more) and decreased total protein (5% or more). Hepatomegaly occurred in less than 5% of men treated with leuprolide, while hepatitis and hepatic dysfunction were also reported. Serious drug-induced liver injury (hepatotoxicity) was reported in both men and women treated with leuprolide in postmarketing experience.[66709] [66721] [43800] [42683] [51299] [68727]

      Hypercholesterolemia has been reported with leuprolide treatment. In women with normal baseline cholesterol, the mean cholesterol increase was 16 to 17 mg/dL in women with endometriosis (p less than 0.03) and 11 to 29 mg/dL in women with uterine fibroids; after 24 weeks of follow-up, the percent-change from baseline was 9.2% for total cholesterol, 7.4% for HDL, 10.9% for LDL, 5% for the LDL/HDL ratio, and 17.5% for triglycerides; the major impact of adding norethindrone to treatment was a decrease in HDL cholesterol and an increase in the LDL/HDL ratio. Lipid concentrations outside the normal range at week 0 and week 24 of leuprolide treatment in women included total cholesterol (more than 240 mg/dL; 15% and 23%), HDL cholesterol (less than 40 mg/dL; 15% and 10%), LDL cholesterol (more than 160 mg/dL; 0% and 8%), LDL/HDL ratio (more than 4; 0% and 3%); the percentage of women with triglyceride concentrations outside the normal range (hypertriglyceridemia) was unchanged (13%). Changes from baseline tended to be greater at week 52; after treatment, mean serum lipid concentrations in women with follow-up data returned to pretreatment values.[42683] [51299] At least 5% of men with prostate cancer treated with leuprolide experienced hyperlipidemia (total cholesterol, LDL cholesterol, triglycerides) and/or decreased HDL cholesterol. In men treated with Lupron Depot 45 mg every 6 months, 28.5% had grade 1 or 2 increases in cholesterol at baseline; grade 1 or 2 increases (200 to 300 mg/dL) during the study occurred in 55%, grade 2 increases (301 to 400 mg/dL) in 3.3%, and grade 3 increases (greater than 400 mg/dL) in 0.7% of men.[43800] [68727]

      A goiter occurred in less than 2% of children with central precocious puberty treated with leuprolide in one clinical trial.[41676] Thyroid enlargement, thyroid nodule, and a hard nodule in the throat were each reported in less than 5% of men with prostate cancer treated with leuprolide.[66721]

      Edema was generally reported in 14.3% or fewer men with prostate cancer and women with endometriosis or fibroids who received leuprolide, although 1 small study suggested the incidence was higher in orchiectomized men compared to nonorchiectomized (20.8% vs. 8.2%). Swelling of the temporal bone occurred in less than 5% of men, while facial swelling/edema was also reported. Peripheral edema occurred in 12% or fewer men treated with leuprolide and in less than 2% of children.[66709] [45097] [66721] [43800] [65368] [41676] [42683] [51299]

      New primary malignancy has been reported in men with prostate cancer treated with leuprolide including bladder cancer (less than 5%), cancer of the skin/ear (less than 5%), and a generalized mass.[41676] [66721] [66709] In one study, a second primary neoplasm was emergent in 7.3% of men who received leuprolide including basal cell carcinoma, bladder transitional cell carcinoma, lung cancer, malignant melanoma, non-Hodgkin's lymphoma, and squamous cell carcinoma; however, none of these cases were felt to be related to treatment.[43800] A cervix disorder/neoplasm occurred in less than 2% of children with central precocious puberty who received leuprolide.[41676]

      Severe cutaneous adverse reactions (SCARs), including toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome (SJS), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP) occurred in patients treated with leuprolide; some cases also had visceral involvement and/or required skin grafts. Monitor patients for SCARs and educate patients about the signs and symptoms (e.g., a prodrome of fever, flu-like symptoms, mucosal lesions, progressive skin rash, or lymphadenopathy). If a SCAR is suspected, interrupt therapy until the etiology has been determined; a dermatology consult is recommended. Permanently discontinue leuprolide for grade 4 skin reactions or confirmed SCARs.[43800]

      Revision Date: 04/07/2024, 02:01:29 PM

      References

      31507 - Randeva HS, Schoebel J, Byrne J, et al. Classical pituitary apoplexy: clinical features, management, and outcome. Clin Endocrinol 1999;51:181-8.31508 - Faustini-Fustini M. Pituitary apoplexy after leuprolide administration for carcinoma of the prostate: what's new? Clin Endocrinol 1997;46:378.40127 - Food and Drug Administration (US FDA) News Release. Ongoing Safety Review of GnRH Agonists and possible increased risk of diabetes and certain cardiovascular diseases. . Retrieved May 3, 2010. Available on the World Wide Web at: http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm210576.htm.41676 - Lupron Depot-Ped (leuprolide acetate for depot suspension) package insert. North Chicago, IL: Abbott Laboratories; 2023 April.42122 - Food and Drug Administration (US FDA) Drug Safety Communication. Updated to ongoing safety review of GnRH Agonists and notification to manufacturers of GnRH Agonists to add new safety information to labeling regarding increased risk of diabetes and certain cardiovascular diseases. Retrieved October 20, 2010. Available on the World Wide Web at: http://www.fda.gov/Drugs/DrugSafety/ucm229986.htm.42683 - Lupron Depot-3 month 11.25 mg (leuprolide acetate injection, powder, lyophilized, for suspension) package insert. Osaka, Japan: Takeda Pharmaceutical Company Limited; 2019 March.43800 - Lupron Depot (leuprolide acetate for depot suspension) package insert. North Chicago, IL: AbbVie Inc; 2024 March.45097 - Eligard (leuprolide acetate) package insert. Fort Collins, CO: Tolmar, Inc.; 2024 Jan.51299 - Lupron Depot 1 month 3.75 mg (leuprolide acetate) suspension package insert. Osaka, Japan: Takeda Pharmaceutical Company Limited; 2021 Jan.63289 - Fluker M, Grifo J, Leader A, et al. Efficacy and safety of ganirelix acetate versus leuprolide acetate in women undergoing controlled ovarian hyperstimulation. Fertil Steril 2001;75:38-45.65368 - Leuprolide acetate (Fensolvi) package insert. Fort Collins, CO: Tolmar, Inc.; 2022 April.66709 - Camcevi (leuprolide) injectable emulsion, for subcutaneous use package insert. Taiwan: Foresee Pharmaceuticals Co., Ltd.; 2024 March.66721 - Lupron (leuprolide acetate for injection) package insert. North Chicago, IL: AbbVie Inc; 2018 Dec.68727 - Lutrate Depot (leuprolide acetate for depot suspension) package insert. Warren, NJ: Cipla USA, Inc.; 2023 Feb.

      Contraindications/Precautions

      Absolute contraindications are italicized.

      • Gonadotropin-Releasing Hormone (GnRH) analogs hypersensitivity
      • pregnancy
      • apheresis
      • AV block
      • benzyl alcohol hypersensitivity
      • bradycardia
      • brain tumor
      • breast-feeding
      • cardiac disease
      • cardiomyopathy
      • celiac disease
      • cerebrovascular disease
      • contraception requirements
      • depression
      • diabetes mellitus
      • dysfunctional uterine bleeding
      • fever
      • geriatric
      • heart failure
      • human immunodeficiency virus (HIV) infection
      • hyperglycemia
      • hyperlipidemia
      • hyperparathyroidism
      • hypocalcemia
      • hypokalemia
      • hypomagnesemia
      • hypothermia
      • hypothyroidism
      • infertility
      • laboratory test interference
      • long QT syndrome
      • myocardial infarction
      • osteopenia
      • osteoporosis
      • pheochromocytoma
      • pregnancy testing
      • pseudotumor cerebri
      • QT prolongation
      • reproductive risk
      • rheumatoid arthritis
      • seizure disorder
      • serious rash
      • sickle cell disease
      • sleep deprivation
      • spinal cord compression
      • stroke
      • suicidal ideation
      • systemic lupus erythematosus (SLE)
      • tobacco smoking
      • urinary tract obstruction
      • vaginal bleeding

      Patients with benzyl alcohol hypersensitivity should use caution when treated with leuprolide acetate solution for injection as it is formulated with benzyl alcohol. Symptoms of hypersensitivity are usually local, in the form of erythema and induration at the injection site.[66721]

      Leuprolide is contraindicated in patients with Gonadotropin-Releasing Hormone (GnRH) analogs hypersensitivity, hypersensitivity to leuprolide, or hypersensitivity to GnRH; anaphylactic reactions to synthetic GnRH or GnRH agonists have been reported.[30370] [30371] [65368] [41676] [42683] [43800] [45097] [66709] [66721] [51299]

      Leuprolide may cause a sudden onset or worsening of prostate cancer (flare) due to transient increases in testosterone levels. Some patients may experience a temporary worsening of symptoms during the first few weeks for treatment, including bone pain, neuropathy, hematuria, or bladder outlet obstruction, which can be managed symptomatically. As with other LH-RH agonists, isolated cases of spinal cord compression have been observed, which may contribute to paralysis with or without fatal complications. Monitor patients for symptoms of tumor flare during the first few weeks of treatment; closely monitor patients with urinary tract obstruction or metastatic vertebral lesions for new or worsening symptoms.[66721] [43800] [45097] [66709] [68727]

      Since leuprolide suppresses the pituitary-gonadal axis, laboratory test interference may occur with diagnostic tests for pituitary insufficiency or other pituitary-gonadal function conducted during treatment and after cessation of therapy.[45097] [66721] [43800] Normal function of the pituitary-gonadal system is usually restored within 4 to 12 weeks after treatment is discontinued;[66721] [43800] [68727] in pediatric patients, normal function may be restored within 6 months.[41676]

      Leuprolide therapy should not be administered to women with dysfunctional uterine bleeding or undiagnosed vaginal bleeding. During the early phase of leuprolide therapy or after subsequent doses, sex steroids temporarily rise above baseline because of a transient stimulatory effect of the drug; an increase in symptoms may be observed during the first weeks of therapy.[41676] [42683] [51299] In pediatric patients, an increase in clinical signs and symptoms of puberty, including vaginal bleeding, may be observed during this time.[41676]

      Carefully weigh the risks and benefits of leuprolide therapy in patients with osteopenia or osteoporosis, as well as in patients with risk factors for decreased bone mineral density (BMD) such as chronic alcohol use (more than 3 units per day), tobacco smoking, strong family history of osteoporosis, or chronic use of drugs that can decrease BMD such as anticonvulsants or corticosteroids.[51299] [42683] Gonadotropin Releasing Hormone (GnRH) analog therapy increases the risk of reduced BMD and may have particular relevance for people 65 years and older.[51299] [42683] [66721] [43800] [45097] [41676] [68727] The duration of therapy for the treatment of endometriosis and fibroids should not exceed 12 months due to the risk of loss of BMD. The addition of hormone replacement therapy (norethindrone acetate) to leuprolide therapy for endometriosis or uterine fibroids may be effective in reducing bone mineral loss in women. Once norethindrone is added, do not retreat with leuprolide without combination norethindrone; assess BMD prior to retreatment with leuprolide/norethindrone.[51299] [42683] It can be anticipated that long periods of medical castration in men with prostate cancer will also have effects on bone density.[66721] [43800] [45097] [68727] Additionally, reduced BMD has been reported in published literature and postmarketing reports in pediatric patients with central precocious puberty. Published studies have indicated that after discontinuation of leuprolide therapy, subsequent bone mass accrual is preserved and peak bone mass in late adolescence does not seem to be affected.[41676]

      Carefully evaluate cardiovascular risk factors when determining a treatment plan for individuals with prostate cancer that are treated with leuprolide. An increased risk of developing myocardial infarction, sudden cardiac death, and stroke has been reported in association with the use of Gonadotropin Releasing Hormone (GnRH) agonists in men; the risk appears to be low based on the reported odds ratios. Monitor patients for signs and symptoms suggestive of cardiac disease; if cardiovascular disease develops, manage according to current clinical practice.[66721] [43800] [45097] [66709] [68727] At this time, there are no known comparable studies evaluating the risk of cardiovascular disease in other individuals taking GnRH agonists for other indications.[42122]

      Use leuprolide with caution in patients with diabetes mellitus or a history of hyperlipidemia. Metabolic changes including hyperglycemia, diabetes mellitus, and hyperlipidemia have been reported in men receiving Gonadotropin Releasing Hormone (GnRH) agonists; diabetes has also been reported in postmarketing experience in pediatric studies with leuprolide. Non-alcoholic fatty liver disease including cirrhosis has been reported in postmarketing experience in adults treated with leuprolide.[66709] [45097] [66721] [43800] [65368] [41676] [68727] Hyperglycemia may represent the development of diabetes or worsening of glycemic control in patients with pre-existing diabetes. Monitor for changes in serum lipids, blood glucose, and/or glycosylated hemoglobin (HbA1c) periodically in men receiving leuprolide therapy; manage according to current clinical practice.[66709] [45097] [66721] [43800] [68727] There are no known comparable epidemiologic studies evaluating the risk of diabetes in women taking GnRH agonists.[40127]

      Androgen deprivation therapy (e.g., leuprolide) may prolong the QT interval. Consider whether the benefits of leuprolide therapy outweigh the potential risk for QT prolongation in patients with congenital long QT syndrome, electrolyte imbalance (e.g., hypokalemia, hypomagnesemia, hypocalcemia), congestive heart failure, or in patients receiving medications known to prolong the QT interval. Correct any electrolyte abnormalities and consider periodic monitoring of electrocardiograms and electrolytes. Also, use leuprolide with caution in patients with conditions that may increase the risk of QT prolongation including bradycardia, AV block, heart failure, stress-related cardiomyopathy, myocardial infarction, stroke, hypomagnesemia, hypokalemia, hypocalcemia, or in patients receiving medications known to cause electrolyte imbalances. Female patients, people 65 years and older, patients with sleep deprivation, pheochromocytoma, sickle cell disease, hypothyroidism, hyperparathyroidism, hypothermia, systemic inflammation (e.g., human immunodeficiency virus (HIV) infection, fever, and some autoimmune diseases including rheumatoid arthritis, systemic lupus erythematosus (SLE), and celiac disease) and patients undergoing apheresis procedures (e.g., plasmapheresis [plasma exchange], cytapheresis) may also be at increased risk for QT prolongation.[28432] [28457] [43800] [56592] [65180] [66721] [45097] [66709] [68727]

      Use leuprolide with caution in patients with a pre-existing 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. Manage patients receiving leuprolide who experience convulsions according to current clinical practice.[41676] [43800] [51299] [66709] [42683] [65368] [45097] [66721] [68727] [45097]

      Use leuprolide with caution in patients with depression and emotional instability; monitor patients for worsening of psychiatric symptoms during treatment with leuprolide. Refer patients with new or worsening depression to a mental health professional, as appropriate. 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.[41676] [65368] [51299] [42683]

      Use leuprolide with caution in geriatric patients. First, geriatric patients may be at increased risk for QT prolongation when receiving leuprolide. Second, GnRH analog therapy increases the risk of reduced bone mineral density, which may be particularly relevant for geriatric patients who may be more likely to have osteopenia or osteoporosis.[28432] [28457] [43800] [56592] [65180] [66721] [42683] [51299] [66709] [45097] [68727]

      Gonadotropin releasing hormone (GnRH) agonists, including leuprolide, have been associated with cases of pseudotumor cerebri (idiopathic intracranial hypertension) in pediatric patients. Monitor for signs and symptoms including headache, papilledema, blurred vision, diplopia, loss of vision, pain behind the eye or pain with eye movement, tinnitus, dizziness, and nausea.[41676] [65368]

      Based on findings in animal studies and mechanism of action, leuprolide can cause fetal harm, including early pregnancy loss, when administered to a pregnant woman. Formulations of leuprolide acetate used for indications that may involve treatment of individuals capable of becoming pregnant (i.e., Fensolvi, Lupron Depot-Ped, Lupron Depot 3.75 mg, and Lupron Depot 11.25 mg) are contraindicated for use during pregnancy. In animal developmental and reproductive toxicology studies, administration of a monthly formulation of leuprolide on day 6 of pregnancy (sustained exposure was expected throughout the period of organogenesis) caused adverse embryo-fetal toxicity in animals at doses less than the human dose based on body surface area (BSA) using an estimated daily dose. A similar rat study also showed increased fetal mortality and decreased fetal weights but no major fetal abnormalities at doses less than the recommended human dose based on BSA using an estimated daily dose. Advise pregnant individuals and females of reproductive potential of the potential risk to the fetus.[28432] [28457] [42683] [43800] [45097] [51299] [56592] [65180] [65368] [41676] [66709] [66721] [68727]

      Serious rash and skin disease, including toxic epidermal necrolysis (TEN), Stevens Johnson syndrome (SJS), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP) occurred in patients treated with leuprolide; some cases also had visceral involvement and/or required skin grafts. Monitor patients for severe cutaneous adverse reactions (SCARs) and educate patients about the signs and symptoms (e.g., a prodrome of fever, flu-like symptoms, mucosal lesions, progressive skin rash, or lymphadenopathy). If a SCAR is suspected, interrupt therapy until the etiology has been determined; a dermatology consult is recommended. Permanently discontinue leuprolide for grade 4 skin reactions or confirmed SCARs.[43800]

      Counsel patients about the reproductive risk and contraception requirements during leuprolide treatment. Leuprolide can cause fetal harm or early pregnancy loss if used during pregnancy. Exclude pregnancy (e.g., perform pregnancy testing) prior to initiating leuprolide treatment if clinically indicated. When used at the recommended dose and dosing interval, leuprolide usually reduces fertility; however, contraception is not ensured by taking leuprolide. Individuals capable of becoming pregnant should use effective non-hormonal contraception during leuprolide treatment. Based on its pharmacodynamic effects of decreasing secretion of gonadal steroids, reduced fertility or infertility is expected while on treatment with leuprolide. Clinical and pharmacologic studies in adults with leuprolide acetate and similar analogs have shown reversibility of fertility suppression when the drug is discontinued after continuous administration for periods of up to 24 weeks.[66709] [45097] [43800] [41676] [65368] [51299] [42683] [66721] [68727]

      There are no data regarding the presence of leuprolide in human milk, the effects on a breast-fed infant, or the effects on milk production. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition when treating lactating individuals with Lupron Depot 3.25 mg, Lupron Depot 11.25 mg, Lupron Depot-Ped, or Fensolvi.[51299] [42683] [41676] [65368] Although leuprolide products used for prostate cancer treatment (e.g., Lupron, Lupron Depot, Eligard, and Camcevi) are not usually indicated in individuals that would be breast-feeding, advise such individuals to discontinue breast-feeding if they are receiving treatment with these products.[66721] [43800] [45097] [66709] [68727]

      Revision Date: 04/07/2024, 02:01:29 PM

      References

      28432 - Roden, DM. Drug-induced prolongation of the QT interval. New Engl J Med 2004;350:1013-22.28457 - Crouch MA, Limon L, Cassano AT. Clinical relevance and management of drug-related QT interval prolongation. Pharmacotherapy 2003;23:881-908.30370 - Potashnik G, Lunenfeld E, Spitz E, et al. Anaphylactic reaction to gonadotropin-releasing hormone. N Engl J Med 1993;328:815.30371 - Letterie GS, Stevenson D, Shah A. Recurrent anaphylaxis to a depot form of GnRH analogue. Obstet Gynecol 1991;78(5 pt 2):943.40127 - Food and Drug Administration (US FDA) News Release. Ongoing Safety Review of GnRH Agonists and possible increased risk of diabetes and certain cardiovascular diseases. . Retrieved May 3, 2010. Available on the World Wide Web at: http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm210576.htm.41676 - Lupron Depot-Ped (leuprolide acetate for depot suspension) package insert. North Chicago, IL: Abbott Laboratories; 2023 April.42122 - Food and Drug Administration (US FDA) Drug Safety Communication. Updated to ongoing safety review of GnRH Agonists and notification to manufacturers of GnRH Agonists to add new safety information to labeling regarding increased risk of diabetes and certain cardiovascular diseases. Retrieved October 20, 2010. Available on the World Wide Web at: http://www.fda.gov/Drugs/DrugSafety/ucm229986.htm.42683 - Lupron Depot-3 month 11.25 mg (leuprolide acetate injection, powder, lyophilized, for suspension) package insert. Osaka, Japan: Takeda Pharmaceutical Company Limited; 2019 March.43800 - Lupron Depot (leuprolide acetate for depot suspension) package insert. North Chicago, IL: AbbVie Inc; 2024 March.45097 - Eligard (leuprolide acetate) package insert. Fort Collins, CO: Tolmar, Inc.; 2024 Jan.51299 - Lupron Depot 1 month 3.75 mg (leuprolide acetate) suspension package insert. Osaka, Japan: Takeda Pharmaceutical Company Limited; 2021 Jan.56592 - van Noord C, Eijgelsheim M, Stricker BH. Drug- and non-drug-associated QT interval prolongation. Br J Clin Pharmacol 2010;70(1):16-23.65180 - Woosley RL, Heise CW, Gallo T, et al. QTFactors List. Oro Valley, AZ: AZCERT, Inc.; Accessed March 31, 2020. Available on the World Wide Web at: https://crediblemeds.org/ndfa-list/65368 - Leuprolide acetate (Fensolvi) package insert. Fort Collins, CO: Tolmar, Inc.; 2022 April.66709 - Camcevi (leuprolide) injectable emulsion, for subcutaneous use package insert. Taiwan: Foresee Pharmaceuticals Co., Ltd.; 2024 March.66721 - Lupron (leuprolide acetate for injection) package insert. North Chicago, IL: AbbVie Inc; 2018 Dec.68727 - Lutrate Depot (leuprolide acetate for depot suspension) package insert. Warren, NJ: Cipla USA, Inc.; 2023 Feb.

      Mechanism of Action

      Leuprolide is a synthetic nonapeptide analog of naturally occurring Gonadotropin Releasing Hormone (GnRH) that possesses greater potency than the natural hormone. As a long-acting GnRH agonist, it acts as a potent inhibitor of gonadotropin secretion (luteinizing hormone [LH] and follicle stimulating hormone [FSH]) when given continuously in therapeutic doses. In both animal and human studies, after an initial stimulation of pituitary gonadotropins, chronic administration results in a down-regulation of GnRH receptors, reduction in the release of LH and FSH, and consequent suppression of ovarian and testicular steroidogenesis. Consequently, tissues and functions that depend on gonadal steroids for their maintenance become quiescent. This effect is reversible after discontinuation of therapy.[66709][45097][66721][43800][65368][41676][42683][51299][68727]

      In humans, subcutaneous administration of single daily doses of leuprolide initial increases circulating levels of LH and FSH, which transiently increases levels of gonadal steroids (testosterone and dihydrotestosterone in males, and estrone and estradiol in premenopausal females). However, continuous daily administration decreases LH and FSH concentrations. In males, testosterone concentrations are reduced to below castration levels (50 ng/dL or less) within 2 to 4 weeks after initiation of treatment; castration levels of testosterone in men with prostate cancer have been demonstrated for up to 7 years.[66709][45097][66721][43800][68727] Normal function of the pituitary-gonadal system is usually restored within 3 months after treatment is discontinued; diagnostic tests of pituitary gonadotropic and gonadal functions conducted during treatment and for up to 3 months after discontinuation may be affected.[42683][51299]

      Administration of leuprolide inhibits growth of certain hormone-dependent tumors (prostatic tumors in Noble and Dunning male rats and DMBA-induced mammary tumors in female rats) as well as atrophy of the reproductive organs.[66721][43800][68727]

      Revision Date: 04/07/2024, 02:01:29 PM

      References

      41676 - Lupron Depot-Ped (leuprolide acetate for depot suspension) package insert. North Chicago, IL: Abbott Laboratories; 2023 April.42683 - Lupron Depot-3 month 11.25 mg (leuprolide acetate injection, powder, lyophilized, for suspension) package insert. Osaka, Japan: Takeda Pharmaceutical Company Limited; 2019 March.43800 - Lupron Depot (leuprolide acetate for depot suspension) package insert. North Chicago, IL: AbbVie Inc; 2024 March.45097 - Eligard (leuprolide acetate) package insert. Fort Collins, CO: Tolmar, Inc.; 2024 Jan.51299 - Lupron Depot 1 month 3.75 mg (leuprolide acetate) suspension package insert. Osaka, Japan: Takeda Pharmaceutical Company Limited; 2021 Jan.65368 - Leuprolide acetate (Fensolvi) package insert. Fort Collins, CO: Tolmar, Inc.; 2022 April.66709 - Camcevi (leuprolide) injectable emulsion, for subcutaneous use package insert. Taiwan: Foresee Pharmaceuticals Co., Ltd.; 2024 March.66721 - Lupron (leuprolide acetate for injection) package insert. North Chicago, IL: AbbVie Inc; 2018 Dec.68727 - Lutrate Depot (leuprolide acetate for depot suspension) package insert. Warren, NJ: Cipla USA, Inc.; 2023 Feb.

      Pharmacokinetics

      Leuprolide is administered subcutaneously or intramuscularly; it is not active when administered orally. In vitro binding to human protein ranged from 43% to 49%. The mean steady-state volume of distribution was 27 liters after an IV bolus in healthy male volunteers. The mean systemic clearance of leuprolide was 7.6 L/hour to 8.34 L/hour after an IV bolus in healthy male volunteers, with a terminal elimination half-life estimated to be about 3 hours based on a 2-compartment model.[66709][45097][66721][43800][65368][41676][42683][51299][68727] Leuprolide is metabolized to smaller inactive peptides including a pentapeptide which is the major metabolite (Metabolite I; M1), tripeptides (Metabolites II and III), and a dipeptide (Metabolite IV) which may then be further catabolized.[66709][66721][65368][41676][68727] Plasma concentrations of M1 were approximately 6% of the peak parent drug concentration; one week after dosing, mean M1 concentrations were approximately 20% of mean leuprolide concentrations. Following IM administration of leuprolide to 3 patients, less than 5% of the dose was recovered in the urine as parent and M1 metabolite.[66721][43800][41676][42683][51299] The excretion of leuprolide has not been evaluated with the extended-release subcutaneous formulations (i.e., Eligard, Fensolvi, and Camcevi).[66709][45097][65368]

       

      Affected cytochrome P450 isoenzymes: None

      Leuprolide acetate is primarily degraded by peptidase. Although drug interaction studies have not been conducted, leuprolide is not degraded by CYP450 enzymes thus drug interactions associated with these enzymes are not expected to occur.[66721][42683][51299][41676]

      Route-Specific Pharmacokinetics

      Intramuscular Route

      The Cmax of leuprolide ranged from 4.6 ng/mL to 10.2 ng/mL at 4 hours after a single IM injection of leuprolide 3.75 mg in healthy female volunteers; after the initial rise, leuprolide concentrations began to plateau within 2 days after dosing and remained relatively stable for 4 to 5 weeks with plasma concentrations of about 0.3 ng/mL.[51299] After a single IM injection of leuprolide 11.25 mg in female subjects, a mean plasma concentration of 36.3 ng/mL was observed at 4 hours; mean levels declined to near the lower limit of detection by 12 weeks, with the mean leuprolide concentration from 3 to 12 weeks at 0.23 +/- 0.09 ng/mL. There was no statistically significant difference in changes of serum estradiol concentrations from baseline in a pharmacokinetic/pharmacodynamic study of endometriosis patients treated with leuprolide 3.75 mg IM every 4 weeks or 11.25 mg IM every 12 weeks.[42683]

       

      Mean peak plasma concentrations were 20 ng/mL, 48.9 ng/mL, and 59.3 ng/mL at 4 hours after administration in patients after a single IM injection of Lupron Depot 7.5 mg, 22.5 mg, and 30 mg, respectively; mean peak plasma concentrations of 6.7 ng/mL were observed 2 hours after IM administration of leuprolide acetate 45 mg. Plasma concentrations decreased to 0.36 ng/mL 4 weeks after administration of leuprolide 7.5 mg; 0.67 ng/mL 12 weeks after administration of 22.5 mg; 0.3 ng/mL 16 weeks after administration of 30 mg; and 0.07 ng/mL 24 weeks after administration of 45 mg.[43800] After 2 sequential IM injections of Lutrate Depot 22.5 mg with a 3-month interval, the mean plasma concentration of leuprolide obtained at 2 hours after administration was 46.8 ng/mL; the mean concentration then declined until the next administration.[68727] Plasma concentrations of M1 in prostate cancer patients (n = 5) reached maximum concentrations 2 to 6 hours after dosing.[66721] For the 3-month, 4-month, and 6-month formulations, the initial peak followed by a decline to steady-state concentrations was similar to the release pattern seen with the monthly formulation. Intact leuprolide and an inactive major metabolite could not be distinguished by the assay employed in the studies.[43800][42683][51299] Leuprolide appears to be released at a constant rate following the onset of steady-state concentrations during the third week after dosing, providing steady plasma concentrations through the dosing interval.[43800][42683]

      Subcutaneous Route

      The bioavailability of leuprolide after subcutaneous administration is comparable to that by IV injection.[66721] Leuprolide concentrations are variable, exhibiting an initial rapid increase followed by a rapid decline over the first 3 days before reaching steady concentrations for the remainder of the dosing interval. The mean Cmax of leuprolide mesylate (Camcevi)was 94.5 ng/mL to 99 ng/mL, with mean serum concentrations maintained between 0.497 ng/mL to 2.57 ng/mL after the third day; the median Tmax was 2.1 to 3.2 hours. The mean AUC was between 224 ng x day/mL and 268 ng x day/mL.[66709] The mean Cmax of leuprolide acetate (Eligard) after subcutaneous administration to men with prostate cancer was 25.3 ng/mL for those receiving 7.5 mg once monthly; 127 ng/mL for those receiving 22.5 mg every 3 months; 150 ng/mL for those receiving 30 mg every 4 months, and 82 ng/mL for those receiving 45 mg every 6 months. The Tmax ranged from 3.3 to 5 hours in these patients. Following a single dose, serum concentrations at the end of each dosing interval were 0.42 ng/mL for the 7.5 mg dose; 0.34 ng/mL for the 22.5 mg dose; 0.1 ng/mL for the 30 mg dose; and 0.2 ng/mL for the 45 mg dose. After the initial increase following each subcutaneous injection, serum concentrations ranged from 0.1 ng/mL to 2 ng/mL. There was no evidence of significant accumulation during repeated dosing.[45097]

      Special Populations

      Hepatic Impairment

      The effect of hepatic impairment on the pharmacokinetics of leuprolide has not been evaluated.[66709][45097][66721][65368][41676][42683][51299]

      Renal Impairment

      The effect of renal impairment on the pharmacokinetics of leuprolide has not been evaluated.[66709][45097][66721][65368][41676][42683][51299]

      Pediatrics

      Leuprolide for 1-month administration

      Mean trough plasma concentrations in children with central precocious puberty after initial doses of leuprolide 7.5 mg, 11.25 mg, and 15 mg for 1-month administration were 0.77, 1.25, and 1.59 ng/mL, respectively. Concentrations after 3 and 6 doses were similar to those seen after the first dose.[41676]

       

      Leuprolide for 3-month administration

      In children with central precocious puberty who received a single intramuscular injection of leuprolide 11.25 mg or 30 mg for 3-month administration, leuprolide concentrations increased with increasing dose; mean peak leuprolide plasma concentrations were 19.1 and 52.5 ng/mL at 1 hour for the 11.25 and 30 mg dose levels, respectively. At 2 weeks post dose, the concentrations declined to 0.08 and 0.25 ng/mL for the 11.25 and 30 mg dose levels, respectively. The mean leuprolide plasma concentration remained constant from month 1 to month 3 for both 11.25 and 30 mg doses. Repeated administration did not lead to leuprolide accumulation.[41676]

       

      Leuprolide for 6-month administration

      In children with central precocious puberty who received a single intramuscular injection of leuprolide 45 mg, leuprolide mean peak plasma concentration increased rapidly to 15.7 ng/mL 1 hour post dose and declined to 0.03 ng/mL by week 24. The mean leuprolide plasma concentrations were similar 6 months after the first and second injections indicating no accumulation.[41676] In children with central precocious puberty who received a single subcutaneous injection of leuprolide 45 mg, concentrations peaked 4 hours post dose with a mean peak leuprolide plasma concentration of 212.3 ng/mL. Absorption occurred in 2 phases, a burst phase followed by a plateau phase. The mean plateau serum leuprolide concentration from 4 to 48 weeks was approximately 0.37 ng/mL with a range of 0.18 to 0.63 ng/mL. There was no accumulation of leuprolide after the second dose.[65368]

      Geriatric

      Age (51 to 88 years) did not have a clinically significant effect on the exposure of leuprolide mesylate.[66709]

      Ethnic Differences

      Race/ethnicity (White, Black, Asian) did not have a clinically significant effect on the exposure of leuprolide mesylate.[66709] Mean concentrations of leuprolide acetate were also similar regardless of race (White, Black, Hispanic).[45097]

      Obesity

      Body weight (54 to 134 kg) did not have a clinically significant effect on the exposure of leuprolide mesylate.[66709]

      Revision Date: 04/07/2024, 02:01:29 PM

      References

      41676 - Lupron Depot-Ped (leuprolide acetate for depot suspension) package insert. North Chicago, IL: Abbott Laboratories; 2023 April.42683 - Lupron Depot-3 month 11.25 mg (leuprolide acetate injection, powder, lyophilized, for suspension) package insert. Osaka, Japan: Takeda Pharmaceutical Company Limited; 2019 March.43800 - Lupron Depot (leuprolide acetate for depot suspension) package insert. North Chicago, IL: AbbVie Inc; 2024 March.45097 - Eligard (leuprolide acetate) package insert. Fort Collins, CO: Tolmar, Inc.; 2024 Jan.51299 - Lupron Depot 1 month 3.75 mg (leuprolide acetate) suspension package insert. Osaka, Japan: Takeda Pharmaceutical Company Limited; 2021 Jan.65368 - Leuprolide acetate (Fensolvi) package insert. Fort Collins, CO: Tolmar, Inc.; 2022 April.66709 - Camcevi (leuprolide) injectable emulsion, for subcutaneous use package insert. Taiwan: Foresee Pharmaceuticals Co., Ltd.; 2024 March.66721 - Lupron (leuprolide acetate for injection) package insert. North Chicago, IL: AbbVie Inc; 2018 Dec.68727 - Lutrate Depot (leuprolide acetate for depot suspension) package insert. Warren, NJ: Cipla USA, Inc.; 2023 Feb.

      Pregnancy/Breast-feeding

      pregnancy

      Based on findings in animal studies and mechanism of action, leuprolide can cause fetal harm, including early pregnancy loss, when administered to a pregnant woman. Formulations of leuprolide acetate used for indications that may involve treatment of individuals capable of becoming pregnant (i.e., Fensolvi, Lupron Depot-Ped, Lupron Depot 3.75 mg, and Lupron Depot 11.25 mg) are contraindicated for use during pregnancy. In animal developmental and reproductive toxicology studies, administration of a monthly formulation of leuprolide on day 6 of pregnancy (sustained exposure was expected throughout the period of organogenesis) caused adverse embryo-fetal toxicity in animals at doses less than the human dose based on body surface area (BSA) using an estimated daily dose. A similar rat study also showed increased fetal mortality and decreased fetal weights but no major fetal abnormalities at doses less than the recommended human dose based on BSA using an estimated daily dose. Advise pregnant individuals and females of reproductive potential of the potential risk to the fetus.[28432] [28457] [42683] [43800] [45097] [51299] [56592] [65180] [65368] [41676] [66709] [66721] [68727]

      breast-feeding

      There are no data regarding the presence of leuprolide in human milk, the effects on a breast-fed infant, or the effects on milk production. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition when treating lactating individuals with Lupron Depot 3.25 mg, Lupron Depot 11.25 mg, Lupron Depot-Ped, or Fensolvi.[51299] [42683] [41676] [65368] Although leuprolide products used for prostate cancer treatment (e.g., Lupron, Lupron Depot, Eligard, and Camcevi) are not usually indicated in individuals that would be breast-feeding, advise such individuals to discontinue breast-feeding if they are receiving treatment with these products.[66721] [43800] [45097] [66709] [68727]

      Revision Date: 04/07/2024, 02:01:29 PM

      References

      28432 - Roden, DM. Drug-induced prolongation of the QT interval. New Engl J Med 2004;350:1013-22.28457 - Crouch MA, Limon L, Cassano AT. Clinical relevance and management of drug-related QT interval prolongation. Pharmacotherapy 2003;23:881-908.41676 - Lupron Depot-Ped (leuprolide acetate for depot suspension) package insert. North Chicago, IL: Abbott Laboratories; 2023 April.42683 - Lupron Depot-3 month 11.25 mg (leuprolide acetate injection, powder, lyophilized, for suspension) package insert. Osaka, Japan: Takeda Pharmaceutical Company Limited; 2019 March.43800 - Lupron Depot (leuprolide acetate for depot suspension) package insert. North Chicago, IL: AbbVie Inc; 2024 March.45097 - Eligard (leuprolide acetate) package insert. Fort Collins, CO: Tolmar, Inc.; 2024 Jan.51299 - Lupron Depot 1 month 3.75 mg (leuprolide acetate) suspension package insert. Osaka, Japan: Takeda Pharmaceutical Company Limited; 2021 Jan.56592 - van Noord C, Eijgelsheim M, Stricker BH. Drug- and non-drug-associated QT interval prolongation. Br J Clin Pharmacol 2010;70(1):16-23.65180 - Woosley RL, Heise CW, Gallo T, et al. QTFactors List. Oro Valley, AZ: AZCERT, Inc.; Accessed March 31, 2020. Available on the World Wide Web at: https://crediblemeds.org/ndfa-list/65368 - Leuprolide acetate (Fensolvi) package insert. Fort Collins, CO: Tolmar, Inc.; 2022 April.66709 - Camcevi (leuprolide) injectable emulsion, for subcutaneous use package insert. Taiwan: Foresee Pharmaceuticals Co., Ltd.; 2024 March.66721 - Lupron (leuprolide acetate for injection) package insert. North Chicago, IL: AbbVie Inc; 2018 Dec.68727 - Lutrate Depot (leuprolide acetate for depot suspension) package insert. Warren, NJ: Cipla USA, Inc.; 2023 Feb.

      Interactions

      Level 1 (Severe)

      • Cisapride
      • Dronedarone
      • Ketoconazole
      • Levoketoconazole
      • Pimozide
      • Thioridazine

      Level 2 (Major)

      • Adagrasib
      • Amiodarone
      • Amisulpride
      • Amoxapine
      • Amoxicillin; Clarithromycin; Omeprazole
      • Anagrelide
      • Androgens
      • Arsenic Trioxide
      • Artemether; Lumefantrine
      • Asenapine
      • Azithromycin
      • Bedaquiline
      • Brexpiprazole
      • Buprenorphine
      • Buprenorphine; Naloxone
      • Cariprazine
      • Ceritinib
      • Chloroquine
      • Chlorpromazine
      • Citalopram
      • Clarithromycin
      • Codeine; Phenylephrine; Promethazine
      • Codeine; Promethazine
      • Crizotinib
      • Danazol
      • Desflurane
      • Deutetrabenazine
      • Dextromethorphan; Quinidine
      • Disopyramide
      • Dofetilide
      • Droperidol
      • Eliglustat
      • Encorafenib
      • Entrectinib
      • Eribulin
      • Erythromycin
      • Esterified Estrogens; Methyltestosterone
      • Fexinidazole
      • Flecainide
      • Fluphenazine
      • Foscarnet
      • Glasdegib
      • Halogenated Anesthetics
      • Haloperidol
      • Hydroxychloroquine
      • Ibutilide
      • Iloperidone
      • Inotuzumab Ozogamicin
      • Isoflurane
      • Ivosidenib
      • Lansoprazole; Amoxicillin; Clarithromycin
      • Lefamulin
      • Lenvatinib
      • Lopinavir; Ritonavir
      • Lorcaserin
      • Loxapine
      • Macimorelin
      • Maprotiline
      • Methadone
      • Methyldopa
      • Methyltestosterone
      • Metoclopramide
      • Midostaurin
      • Mobocertinib
      • Molindone
      • Moxifloxacin
      • Nilotinib
      • Olanzapine
      • Olanzapine; Fluoxetine
      • Olanzapine; Samidorphan
      • Ondansetron
      • Osimertinib
      • Oxaliplatin
      • Oxandrolone
      • Oxymetholone
      • Ozanimod
      • Pacritinib
      • Paliperidone
      • Panobinostat
      • Pazopanib
      • Pentamidine
      • Perphenazine
      • Perphenazine; Amitriptyline
      • Pimavanserin
      • Pitolisant
      • Ponesimod
      • Prasterone, Dehydroepiandrosterone, DHEA (Dietary Supplements)
      • Prasterone, Dehydroepiandrosterone, DHEA (FDA-approved)
      • Procainamide
      • Promethazine
      • Promethazine; Dextromethorphan
      • Promethazine; Phenylephrine
      • Propafenone
      • Quetiapine
      • Quinidine
      • Quinine
      • Quizartinib
      • Ramelteon
      • Ribociclib
      • Ribociclib; Letrozole
      • Risperidone
      • Saquinavir
      • Selpercatinib
      • Sevoflurane
      • Siponimod
      • Sorafenib
      • Sotalol
      • Testosterone
      • Tetrabenazine
      • Thiothixene
      • Toremifene
      • Trandolapril; Verapamil
      • Trazodone
      • Trifluoperazine
      • Valbenazine
      • Vandetanib
      • Vemurafenib
      • Verapamil
      • Vonoprazan; Amoxicillin; Clarithromycin
      • Ziprasidone

      Level 3 (Moderate)

      • Alfuzosin
      • Apomorphine
      • Aripiprazole
      • Atomoxetine
      • Bismuth Subcitrate Potassium; Metronidazole; Tetracycline
      • Bismuth Subsalicylate; Metronidazole; Tetracycline
      • Cabotegravir; Rilpivirine
      • Ciprofloxacin
      • Clofazimine
      • Clozapine
      • Dasatinib
      • Dexmedetomidine
      • Dolasetron
      • Dolutegravir; Rilpivirine
      • Donepezil
      • Donepezil; Memantine
      • Efavirenz
      • Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate
      • Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate
      • Emtricitabine; Rilpivirine; Tenofovir alafenamide
      • Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate
      • Escitalopram
      • Etrasimod
      • Fingolimod
      • Fluconazole
      • Fluoxetine
      • Fluvoxamine
      • Fostemsavir
      • Gemifloxacin
      • Gemtuzumab Ozogamicin
      • Gilteritinib
      • Granisetron
      • Hydroxyzine
      • Itraconazole
      • Lapatinib
      • Levofloxacin
      • Lithium
      • Lofexidine
      • Loperamide
      • Loperamide; Simethicone
      • Mefloquine
      • Metronidazole
      • Mifepristone
      • Mirtazapine
      • Ofloxacin
      • Osilodrostat
      • Pasireotide
      • Posaconazole
      • Primaquine
      • Prochlorperazine
      • Ranolazine
      • Rilpivirine
      • Romidepsin
      • Sertraline
      • Sodium Stibogluconate
      • Solifenacin
      • Sunitinib
      • Tacrolimus
      • Tamoxifen
      • Telavancin
      • Tolterodine
      • Triclabendazole
      • Vardenafil
      • Venlafaxine
      • Voclosporin
      • Voriconazole
      • Vorinostat
      Adagrasib: (Major) Concomitant use of adagrasib and androgen deprivation therapy (i.e., leuprolide) increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [43800] [68325] 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. [28261] [43800] Amiodarone: (Major) Concomitant use of amiodarone and androgen deprivation therapy (i.e., leuprolide) increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after drug discontinuation. [28224] [28432] [28457] [43800] Amisulpride: (Major) Monitor ECGs for QT prolongation when amisulpride is administered with leuprolide. Amisulpride causes dose- and concentration- dependent QT prolongation. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval. [43800] [65068] 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. [28558] [45411] 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. [28225] [28238] [43800] 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. [30163] [43800] 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. [43800] 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. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. [28661] [43800] Aripiprazole: (Moderate) Concomitant use of aripiprazole and androgen deprivation therapy (i.e., leuprolide) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. [42845] [43800] 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. [43800] [59438] 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. [35401] [43800] (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. [35401] [43800] 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. [36343] [43800] Atomoxetine: (Moderate) Concomitant use of atomoxetine and androgen deprivation therapy (i.e., leuprolide) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. [28405] [43800] Azithromycin: (Major) Concomitant use of leuprolide and azithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [28855] [43800] [43974] [65157] [65170] 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. [43800] [52746] Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Moderate) Concomitant use of metronidazole and androgen deprivation therapy (i.e., leuprolide) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. [36894] [43800] Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) Concomitant use of metronidazole and androgen deprivation therapy (i.e., leuprolide) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. [36894] [43800] 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. [45411] [59949] 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. [41235] [43800] [60270] 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. [41235] [43800] [60270] Cabotegravir; 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. [43800] [44376] 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. [45411] [60164] 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. [43800] [57094] Chloroquine: (Major) Avoid coadministration of chloroquine with leuprolide due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Chloroquine is associated with an increased risk of QT prolongation and torsade de pointes (TdP); the risk of QT prolongation is increased with higher chloroquine doses. Androgen deprivation therapy (i.e., leuprolide) may prolong the QT/QTc interval. [28229] [28230] [28231] [29758] [43800] [65157] [65170] 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. [28415] [43065] [43800] Ciprofloxacin: (Moderate) Concomitant use of ciprofloxacin and androgen deprivation therapy (i.e., leuprolide) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. [28432] [28457] [29833] [33144] [33145] [33146] [43411] [43800] [48869] [48871] Cisapride: (Contraindicated) 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. [28978] [43800] [47221] Citalopram: (Major) Concomitant use of leuprolide and citalopram increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [28269] [43800] 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. [28225] [28238] [43800] Clofazimine: (Moderate) Concomitant use of clofazimine and androgen deprivation therapy (i.e., leuprolide) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. [43800] [63936] 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. [28262] [43800] Codeine; Phenylephrine; Promethazine: (Major) Concomitant use of promethazine and leuprolide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [28225] [43800] [45411] [55578] Codeine; Promethazine: (Major) Concomitant use of promethazine and leuprolide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [28225] [43800] [45411] [55578] 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. [43800] [45458] 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. [43800] 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. [32387] [43800] 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. [28457] [28458] [28754] [28755] [28756] [43800] Deutetrabenazine: (Major) Avoid coadministration of leuprolide with deutetrabenazine due to the risk of reduced efficacy of leuprolide. Deutetrabenazine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin-releasing hormone (GnRH) receptors; leuprolide is a GnRH analog. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval. Deutetrabenazine may prolong the QT interval, but the degree of QT prolongation is not clinically significant when deutetrabenazine is administered within the recommended dosage range. [43800] [45411] [61845] Dexmedetomidine: (Moderate) Concomitant use of dexmedetomidine and androgen deprivation therapy (i.e., leuprolide) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. [43800] [67509] 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. [43800] [47357] 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). [28228] [43800] 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. [28221] [28432] [28457] [43800] 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. [42844] [43800] 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. [43800] [44376] 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. [43800] [59321] [59322] 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. [43800] [59321] [59322] Dronedarone: (Contraindicated) 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. [36101] [43800] 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. [28235] [28236] [28737] [43800] [51289] 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. [28442] [43800] Efavirenz; Emtricitabine; 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. [28442] [43800] 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. [28442] [43800] 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. [43800] [57803] 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. [43800] [44376] 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. [43800] [44376] 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. [43800] [63317] 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. [43800] [64567] 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. [42449] [43800] Erythromycin: (Major) Concomitant use of leuprolide and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [43258] [43800] Escitalopram: (Moderate) Concomitant use of escitalopram and androgen deprivation therapy (i.e., leuprolide) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. [28270] [43800] 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. [43800] Etrasimod: (Moderate) Concomitant use of etrasimod and androgen deprivation therapy (i.e., leuprolide) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. Etrasimod has a limited effect on the QT/QTc interval at therapeutic doses but may cause bradycardia and atrioventricular conduction delays which may increase the risk for TdP in patients with a prolonged QT/QTc interval. [43800] [69114] Fexinidazole: (Major) Concomitant use of fexinidazole and androgen deprivation therapy (i.e., leuprolide) increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [43800] [66812] 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. [41823] [43800] 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. [23774] [28752] [43800] Fluconazole: (Moderate) Concomitant use of fluconazole and androgen deprivation therapy (i.e., leuprolide) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. [28674] [43800] Fluoxetine: (Moderate) Concomitant use of fluoxetine and androgen deprivation therapy (i.e., leuprolide) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. [32127] [43800] 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. [28415] [28416] [43800] [45411] 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. [43800] [50507] 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. [28377] [43800] Fostemsavir: (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. Supratherapeutic doses of fostemsavir (2,400 mg twice daily, four times the recommended daily dose) have been shown to cause QT prolongation. Fostemsavir causes dose-dependent QT prolongation. [43800] [65666] 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. [28424] [43800] 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. [43800] [62292] 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. [43800] [63787] 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. [43800] [63777] 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. [31723] [43800] 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. [28457] [28458] [28754] [28755] [28756] [43800] 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. [23500] [23779] [28307] [28415] [43800] [45411] Hydroxychloroquine: (Major) Concomitant use of leuprolide and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [41806] [43800] [65157] [65170] Hydroxyzine: (Moderate) Concomitant use of hydroxyzine and androgen deprivation therapy (i.e., leuprolide) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. [43800] [47129] 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. [41830] [43800] 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. [36146] [43800] [45411] 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. [43800] [62245] 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. [28457] [28458] [28754] [28755] [28756] [43800] 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. [40233] [43800] [57441] 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. [43800] [63368] Ketoconazole: (Contraindicated) Avoid concomitant use of ketoconazole and androgen deprivation therapy (i.e., leuprolide) due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation. [27982] [43800] [67231] Lansoprazole; Amoxicillin; 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. [28225] [28238] [43800] 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. [33192] [43800] 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. [43800] [64576] 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. [43800] [58782] Levofloxacin: (Moderate) Concomitant use of levofloxacin and androgen deprivation therapy (i.e., leuprolide) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. [28421] [28432] [28457] [29833] [33144] [33145] [33146] [43800] [48869] [48871] Levoketoconazole: (Contraindicated) Avoid concomitant use of ketoconazole and androgen deprivation therapy (i.e., leuprolide) due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation. [27982] [43800] [67231] Lithium: (Moderate) Concomitant use of lithium and androgen deprivation therapy (i.e., leuprolide) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. [43800] [59809] [59810] [59811] 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. [43800] [63161] 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. [43800] [60864] 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. [43800] [60864] Lopinavir; Ritonavir: (Major) Avoid coadministration of lopinavir with leuprolide due to the potential for additive QT prolongation. If use together is necessary, obtain a baseline ECG to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Lopinavir is associated with QT prolongation. Androgen deprivation therapy (i.e., leuprolide) may prolong the QT/QTc interval. [28341] [43800] [65157] [65170] 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. [45411] [51065] 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. [43462] [45411] 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. [43800] [62723] 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. [28225] [28759] [43800] 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. [28301] [43800] 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. [28319] [28320] [28321] [28322] [33136] [43800] 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. [29252] [45411] 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. [43800] 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. [28953] [45411] Metronidazole: (Moderate) Concomitant use of metronidazole and androgen deprivation therapy (i.e., leuprolide) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. [36894] [43800] Midostaurin: (Major) Concomitant use of midostaurin and androgen deprivation therapy (i.e., leuprolide) increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [43800] [61906] Mifepristone: (Moderate) Concomitant use of mifepristone and androgen deprivation therapy (i.e., leuprolide) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. [43800] [48697] Mirtazapine: (Moderate) Concomitant use of mirtazapine and androgen deprivation therapy (i.e., leuprolide) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. [40942] [43800] Mobocertinib: (Major) Concomitant use of mobocertinib and androgen deprivation therapy (i.e., leuprolide) increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [43800] [66990] 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. [28820] [45411] 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. [28423] [28432] [28457] [29833] [33144] [33145] [33146] [43800] [48869] [48871] 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. [43800] [58766] Ofloxacin: (Moderate) Concomitant use of ofloxacin and androgen deprivation therapy (i.e., leuprolide) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. [28432] [28457] [29833] [30738] [33144] [33145] [33146] [43800] [48869] [48871] [51299] 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. [28785] [32732] [32734] [32745] [32746] [43800] [45411] Olanzapine; Fluoxetine: (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. [28785] [32732] [32734] [32745] [32746] [43800] [45411] (Moderate) Concomitant use of fluoxetine and androgen deprivation therapy (i.e., leuprolide) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. [32127] [43800] Olanzapine; Samidorphan: (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. [28785] [32732] [32734] [32745] [32746] [43800] [45411] Ondansetron: (Major) Concomitant use of ondansetron and leuprolide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Do not exceed 16 mg of IV ondansetron in a single dose; the degree of QT prolongation associated with ondansetron significantly increases above this dose. [31266] [43800] Osilodrostat: (Moderate) Monitor ECGs in patients receiving osilodrostat with leuprolide. Osilodrostat is associated with dose-dependent QT prolongation. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval. [43800] [65098] 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. [43800] [60297] 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. [41958] [43800] 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. [43800] 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. [43800] Ozanimod: (Major) In general, do not initiate ozanimod in patients taking leuprolide due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Androgen deprivation therapy (i.e., leuprolide) may prolong the QT/QTc interval. [43800] [65169] Pacritinib: (Major) Concomitant use of pacritinib and androgen deprivation therapy (i.e., leuprolide) increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [43800] [67427] 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. [40936] [43800] [45411] 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. [43800] [58821] 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. [43800] [52611] 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. [37098] [43800] 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. [23620] [23778] [28419] [28879] [43800] 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. [28415] [43800] [45411] 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. [28415] [43800] [45411] 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. [43800] [60748] Pimozide: (Contraindicated) 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. [28225] [43463] [43800] [45411] 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. [64562] Ponesimod: (Major) In general, do not initiate ponesimod in patients taking leuprolide due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ponesimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ponesimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Androgen deprivation therapy (i.e., leuprolide) may prolong the QT/QTc interval. [43800] [66527] 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. [32723] [43800] 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. [43800] 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. [43800] 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. [41984] [43800] 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. [28250] [43800] Prochlorperazine: (Moderate) Monitor for reduced efficacy of gonadotropin releasing hormone (GnRH) analogues, such as leuprolide, during intermittent prochlorperazine use; avoid chronic concomitant use. Hyperprolactinemia reduces the number of pituitary GnRH receptors which may reduce leuprolide efficacy. Prolactin elevations have been observed with prochlorperazine use and typically resolve rapidly following discontinuation. [43800] [45411] [69332] Promethazine: (Major) Concomitant use of promethazine and leuprolide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [28225] [43800] [45411] [55578] Promethazine; Dextromethorphan: (Major) Concomitant use of promethazine and leuprolide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [28225] [43800] [45411] [55578] Promethazine; Phenylephrine: (Major) Concomitant use of promethazine and leuprolide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [28225] [43800] [45411] [55578] Propafenone: (Major) Concomitant use of propafenone and leuprolide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [28287] [43800] Quetiapine: (Major) Concomitant use of quetiapine and leuprolide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [29118] [33068] [33072] [43800] 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. [43800] [47357] 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. [31403] [43800] Quizartinib: (Major) Concomitant use of quizartinib and androgen deprivation therapy (i.e., leuprolide) increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [43800] [69220] 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. [31359] [45411] 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. [31938] [43800] 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. [43800] [61816] 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. [43800] [61816] 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. [43800] [44376] 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. [28225] [28414] [43800] 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. [37292] [43800] 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. [28995] [43800] Selpercatinib: (Major) Monitor ECGs more frequently for QT prolongation if coadministration of selpercatinib with leuprolide is necessary due to the risk of additive QT prolongation. Concentration-dependent QT prolongation has been observed with selpercatinib therapy. Androgen deprivation therapy (i.e., leuprolide) may prolong the QT/QTc interval. [43800] [65387] Sertraline: (Moderate) Concomitant use of sertraline and androgen deprivation therapy (i.e., leuprolide) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with sertraline is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 2 times the maximum recommended dose. [28343] [43800] [64391] [64392] [64394] [64395] [64396] 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. [28457] [28458] [28754] [28755] [28756] [43800] 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. [43800] [64031] Sodium Stibogluconate: (Moderate) Concomitant use of sodium stibogluconate and androgen deprivation therapy (i.e., leuprolide) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. [43800] [64608] 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. [30515] [43800] Sorafenib: (Major) Avoid coadministration of sorafenib with leuprolide due to the risk of additive QT prolongation. If concomitant use is unavoidable, monitor electrocardiograms and correct electrolyte abnormalities. An interruption or discontinuation of sorafenib therapy may be necessary if QT prolongation occurs. Sorafenib is associated with QTc prolongation. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval. [31832] [43800] Sotalol: (Major) Concomitant use of sotalol and leuprolide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [28234] [43800] 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. [31970] [43800] 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. [28611] [43800] Tamoxifen: (Moderate) Concomitant use of tamoxifen and androgen deprivation therapy (i.e., leuprolide) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. [43800] [61870] [61871] [61872] [63589] 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. [36615] [43800] 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. [43800] 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. [34389] [43800] [45411] Thioridazine: (Contraindicated) 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. [28225] [28293] [43800] [45411] 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. [45411] [46957] 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. [31112] [43800] 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. [28822] [43800] 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. [28273] [45411] Trazodone: (Major) Concomitant use of trazodone and leuprolide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [38831] [43800] Triclabendazole: (Moderate) Concomitant use of triclabendazole and androgen deprivation therapy (i.e., leuprolide) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. [43800] [63962] 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. [28415] [43800] [45411] Valbenazine: (Major) Avoid concurrent use of leuprolide with valbenazine due to the risk of reduced efficacy of leuprolide. Valbenazine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog. [45411] [61873] 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. [43800] [43901] Vardenafil: (Moderate) Concomitant use of vardenafil and androgen deprivation therapy (i.e., leuprolide) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. [28216] [43800] 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. [43800] [45335] Venlafaxine: (Moderate) Concomitant use of venlafaxine and androgen deprivation therapy (i.e., leuprolide) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. [33715] [43800] 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. [28273] [45411] Voclosporin: (Moderate) Concomitant use of voclosporin and leuprolide may increase the risk of QT prolongation. Consider interventions to minimize the risk of progression to torsades de pointes (TdP), such as ECG monitoring and correcting electrolyte abnormalities, particularly in patients with additional risk factors for TdP. Voclosporin has been associated with QT prolongation at supratherapeutic doses. Androgen deprivation therapy (i.e., leuprolide) may prolong the QT/QTc interval. [43800] [66336] Vonoprazan; Amoxicillin; 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. [28225] [28238] [43800] 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. [28158] [43800] 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. [32789] [43800] 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. [28233] [43800]
      Revision Date: 04/07/2024, 02:01:29 PM

      References

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      Monitoring Parameters

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      • serum testosterone concentrations

      US Drug Names

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      • Viadur
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