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Leuprolide: Drug information

Leuprolide: Drug information
2024© UpToDate, Inc. and its affiliates and/or licensors. All Rights Reserved.
For additional information see "Leuprolide: Patient drug information" and "Leuprolide: Pediatric drug information"

For abbreviations, symbols, and age group definitions show table
Brand Names: US
  • Camcevi;
  • Eligard;
  • Fensolvi (6 Month);
  • Lupron Depot (1-Month);
  • Lupron Depot (3-Month);
  • Lupron Depot (4-Month);
  • Lupron Depot (6-Month);
  • Lupron Depot-Ped (1-Month);
  • Lupron Depot-Ped (3-Month);
  • Lupron Depot-Ped (6-Month)
Brand Names: Canada
  • Eligard;
  • Lupron Depot;
  • Lupron Depot (1-Month);
  • Lupron Depot (3-Month);
  • Lupron Depot 3 Month Kit;
  • Lupron [DSC];
  • Zeulide Depot
Pharmacologic Category
  • Antineoplastic Agent, Gonadotropin-Releasing Hormone Agonist;
  • Gonadotropin Releasing Hormone Agonist
Dosing: Adult

Dosage guidance:

Dosage form information: Do not use a fractional dose of the 3-, 4-, or 6-month depot formulation, or a combination of doses of the monthly depot formulation or any depot formulation due to different release characteristics. Do not use a combination of syringes to achieve a particular dose.

Breast cancer, premenopausal ovarian suppression for fertility preservation during chemotherapy

Breast cancer, premenopausal ovarian suppression for fertility preservation during chemotherapy (off-label use):

Lupron Depot: IM: 3.75 mg every 28 days starting at least 1 week prior to the initiation of chemotherapy and continuing until the end of chemotherapy (Ref).

Breast cancer, premenopausal ovarian suppression during endocrine therapy

Breast cancer, premenopausal ovarian suppression during endocrine therapy (off-label use):

Lupron Depot: IM: 3.75 mg every 4 weeks for ~5 years (Ref).

Breast cancer in male patients, hormone receptor positive

Breast cancer in male patients, hormone receptor positive (off-label use): Note: Should be used in combination with an aromatase inhibitor (Ref).

Adva nced or metastatic disease: IM: 3.75 mg once every 4 weeks (Ref). Endocrine therapy for males with advanced or metastatic, HR+, HER2-negative breast cancer may be sequenced as in females (Ref).

Endometriosis

Endometriosis: Note: Initial treatment (maximum 6 months) may be as monotherapy or combination therapy with norethindrone acetate (add-back therapy). A single retreatment course (maximum 6 months) of leuprolide in combination with norethindrone acetate may be considered if symptoms recur. Monotherapy is not recommended for retreatment. Total duration of therapy (initial plus re-treatment for symptom recurrence) should not exceed 12 months.

Initial therapy: May be used as monotherapy or in combination with norethindrone acetate.

Lupron Depot: IM: 3.75 mg every month for up to 6 months.

Lupron Depot-3 month: IM: 11.25 mg every 3 months for 1 to 2 doses (maximum 6 months).

Symptom recurrence: Administer in combination with norethindrone acetate.

Lupron Depot: IM: 3.75 mg every month for up to 6 months.

Lupron Depot-3 month: IM: 11.25 mg every 3 months for 1 to 2 doses (maximum 6 months).

Hormone therapy for transgender females, assigned male at birth

Hormone therapy for transgender females, assigned male at birth (adjunctive agent) (off-label use): IM (depot) or SUBQ: 3.75 mg monthly or 11.25 mg every 3 months in combination with other appropriate agents (Ref). Lupron Depot should be administered IM and Eligard should be administered SUBQ.

Paraphilia, males

Paraphilia, males (off-label use):

Note: May cause an initial increase in androgen concentrations; concomitant antiandrogen therapy (eg, cyproterone, flutamide) is recommended starting 1 week before and continued for the first month after leuprolide initiation (Ref). Avoid use in patients with osteoporosis (especially in patients with prior fracture) or active pituitary disease (Ref).

Initial test dose: SUBQ: 1 mg once; if no hypersensitivity to the test dose, may proceed to treatment dosing (Ref).

Treatment dosing: Depot IM: 3.75 to 7.5 mg monthly (Ref) or 11.25 mg every 3 months (Ref). If therapy is discontinued, rebound elevation in testosterone levels and recurrence of symptoms may occur; if symptoms recur, retreatment with leuprolide or another agent is recommended (Ref).

Prostate cancer, advanced

Prostate cancer, advanced: Note: Treatment is usually continued after development of metastatic (castration-resistant) disease.

Leuprolide acetate:

Lupron Depot 7.5 mg (monthly): IM: 7.5 mg every month.

Leuprolide Depot (generic, Cipla), Lupron Depot 22.5 mg (3 month): IM: 22.5 mg every 12 weeks.

Lupron Depot 30 mg (4 month): IM: 30 mg every 16 weeks.

Lupron Depot 45 mg (6 month): IM: 45 mg every 24 weeks.

Eligard: SUBQ: 7.5 mg monthly or 22.5 mg every 3 months or 30 mg every 4 months or 45 mg every 6 months.

Leuprolide acetate 5 mg/mL solution: SUBQ: 1 mg daily.

Zeulide Depot [Canadian product]: IM: 3.75 mg once every month or 22.5 mg once every 3 months.

Leuprolide mesylate:

Camcevi: SUBQ:42 mg leuprolide (equivalent to ~48 mg leuprolide mesylate) once every 6 months.

Uterine leiomyomata

Uterine leiomyomata (fibroids):

Note: Prior to combination therapy with iron, consider a 1-month trial period of iron alone; the addition of leuprolide may be considered when response to iron monotherapy is inadequate.

Lupron Depot: IM: 3.75 mg every month for up to 3 months (in combination with iron).

Lupron Depot-3 month: IM: 11.25 mg as a single injection (in combination with iron).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.

Altered kidney function: IM, SUBQ: No dosage adjustment necessary for any degree of kidney impairment (<5% of the drug is eliminated in the urine as parent and major metabolite) (Ref).

Hemodialysis, intermittent (thrice weekly): Not significantly dialyzed (Ref): IM, SUBQ: No supplemental dose or dosage adjustment necessary (Ref). Note: For the IR formulation, when scheduled dose falls on dialysis days, administer after hemodialysis (Ref).

Peritoneal dialysis: Unlikely to be significantly dialyzed: IM, SUBQ: No dosage adjustment necessary (Ref).

CRRT: IM, SUBQ: No dosage adjustment necessary (Ref).

PIRRT (eg, sustained, low-efficiency diafiltration): IM, SUBQ: No dosage adjustment necessary (Ref).

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).

Dosing: Adjustment for Toxicity: Adult

Severe cutaneous adverse reactions (including Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms, and acute generalized exanthematous pustulosis): Interrupt leuprolide therapy until cause of the reaction is determined; consult with dermatologist. Permanently discontinue leuprolide therapy if severe cutaneous adverse reaction is confirmed or other grade 4 skin reactions occur.

Dosing: Older Adult

Refer to adult dosing.

Dosing: Pediatric

(For additional information see "Leuprolide: Pediatric drug information")

Note: Each formulation (including different strengths) has unique release characteristics; do not use partial syringes or a combination of syringes to achieve dose. Dosing regimens and route of administration of international product(s) may vary from US dosage forms; refer to specific international product labeling.

Central precocious puberty

Central precocious puberty (CPP):

Note: Pubertal maturation will resume within months (eg, ~6 to 18 months) after discontinuation of treatment, with wide variability; consider discontinuing leuprolide therapy at the appropriate age for the onset of puberty (eg, when peers would be experiencing puberty). Therapy is typically discontinued at ~10 to 12 years of age, depending on clinical circumstances (Ref).

IM: Children:

Monthly dosing:

Lupron Depot-Ped (monthly formulation):

Fixed dosing: IM: 7.5 mg every 4 weeks; titrate as needed to attain adequate suppression (Ref). A lower starting dose of 3.75 mg every 4 weeks is also effective in most children (Ref).

Weight-directed dosing: Note: Although weight-directed dosing is described by the manufacturer, some experts recommend against this approach for depot formulations (Ref).

≤25 kg: IM: 7.5 mg every 4 weeks; titrate dose in 3.75 mg increments (ie, to the next available dosage form size) every 4 weeks until clinical or laboratory tests indicate adequate suppression.

>25 to 37.5 kg: IM: 11.25 mg every 4 weeks; titrate dose in 3.75 mg increments (ie, to the next available dosage form size) every 4 weeks until clinical or laboratory tests indicate adequate suppression.

>37.5 kg: IM: 15 mg every 4 weeks; titrate dose in 3.75 mg increments (ie, to the next available dosage form size) every 4 weeks until clinical or laboratory tests indicate adequate suppression.

Every-3-month dosing:

Lupron Depot-Ped (3-month formulation) and Lupron Depot: IM: 11.25 mg, 22.5 mg, or 30 mg every 12 weeks. Note: If initiating therapy with the 3-month formulation, some experts begin with 11.25 mg dose and titrate to attain adequate suppression (Ref).

Every-6-month dosing:

Lupron Depot-Ped (6-month formulation): IM: 45 mg every 24 weeks (Ref).

SUBQ: Children ≥2 years:

Long-acting formulation: Fensolvi: SUBQ: 45 mg every 6 months (Ref).

Short-acting formulation: Leuprolide acetate 5 mg/mL solution: SUBQ: Initial: 50 mcg/kg/dose once daily; may titrate dose upward by 10 mcg/kg/day if suppression is not adequate (Ref). Note: Dosage form is no longer approved for this indication; use has been replaced by long-acting formulations which require less frequent dosing (Ref).

Endometriosis

Endometriosis:

Note: Due to ongoing growth and bone maturation in adolescents, leuprolide use in patients <18 years of age should be reserved for patients with pain refractory to conservative surgical therapy (Ref); empiric therapy should not be used (Ref). Although the manufacturer's labeling suggest monotherapy with leuprolide as an option for initial courses, experts suggest that in adolescents, initial leuprolide therapy be in combination with norethindrone with or without conjugated estrogen (add-back therapy). Adolescent patients should also be supplemented with calcium and vitamin D (Ref).

Lupron Depot (monthly formulation): Post-menarche adolescents: IM: 3.75 mg every month for up to 6 months.

Lupron Depot (3-month formulation): Post-menarche adolescents: IM: 11.25 mg every 3 months for up to 2 doses as initial therapy; for retreatment, may repeat course for up to 2 doses; total treatment duration should not exceed 12 months.

Leuprolide Stimulation Test

Leuprolide (GnRHa) Stimulation Test (Female): Limited data available: Children ≥2 years: Leuprolide acetate 5 mg/mL solution: SUBQ: 20 mcg/kg once; measure LH and follicle-stimulating hormone at baseline and after administration (usually 2 spaced measurements ≤120 minutes [eg, 30 and 60 minutes or 60 and 120 minutes]) (Ref).

Uterine leiomyomata

Uterine leiomyomata (fibroids): Note: Use in combination with iron supplementation. Due to ongoing growth and bone maturation in adolescents, consider calcium and vitamin D supplementation with therapy based on experience in adolescents with leuprolide use for endometriosis.

Lupron Depot (monthly formulation): Post-menarche adolescents: IM: 3.75 mg every month for up to 3 months.

Lupron Depot (3-month formulation): Post-menarche adolescents: IM: 11.25 mg as a single injection.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing adjustment for toxicity: Delayed hypersensitivity (including severe cutaneous adverse reactions of Stevens-Johnson syndrome and toxic epidermal necrolysis): Discontinue future leuprolide therapy at first signs/symptoms of a delayed hypersensitivity reaction and manage as clinically indicated.

Dosing: Kidney Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).

Dosing: Hepatic Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).

Adverse Reactions (Significant): Considerations
Decreased bone density

Leuprolide may cause decreased bone mineral density (BMD). Data in pediatric patients with central precocious puberty are conflicting (Ref). Data from use of gonadotropin-releasing hormone (GnRH) agonist therapy in males with prostate cancer show a 2% to 3% decrease in BMD of the hip and spine per year during initial therapy (Ref). Postmarketing claim-based studies show a bone fracture rate of 19.4% in males with prostate cancer receiving androgen deprivation therapy compared to 12.6% to those not receiving therapy (Ref). Bone loss with GnRH agonist therapy in females is less quantified but described as significant and may exceed 1% per month (Ref). In adult females, discontinuation of therapy did not ensure complete recovery of the bone loss (Ref).

Mechanism: Time-related; fundamentally, it is the increase in bone turnover and decrease in BMD that causes adverse skeletal effects (Ref). The imbalance of osteoclast and osteoblast activity is secondary to parathyroid hormone, estrogen, and other sex hormone level changes (Ref).

Onset: Varied; remarkable bone loss may occur after 3 to 6 months of GnRH agonist therapy but is more commonly associated with long-term GnRH therapy (Ref).

Risk factors:

• Treatment duration (Ref)

• Family history of osteoporosis

• Concurrent administration of medications associated with bone loss (eg, antiseizure medications, long-term corticosteroids, aromatase inhibitors) (Ref)

• Lifestyle factors (eg, chronic tobacco or alcohol use, sedentary nature) (Ref)

• Low calcium intake (Ref)

• Vitamin D deficiency (Ref)

• Hypogonadism (Ref)

Hypersensitivity reactions (immediate and delayed)

Immediate hypersensitivity reactions (urticaria, angioedema, anaphylaxis) have been reported (Ref). Recurrent anaphylaxis in response to depot leuprolide has been reported (Ref); with recurrent anaphylaxis or a history of anaphylaxis to multiple unrelated drugs (eg, leuprolide acetate depot and triamcinolone), a reaction to the excipient carboxymethylcellulose should be considered. Delayed hypersensitivity reactions have also been reported, including maculopapular skin rash, mycosis-fungoides-like eruption, serum sickness, and hypersensitivity angiitis (Ref). Injection site granuloma may occur (Ref). Acute generalized exanthematous pustulosis, bullous dermatitis, erythema multiforme, exfoliative dermatitis, drug reaction with eosinophilia and systemic symptoms, Stevens-Johnson syndrome, and toxic epidermal necrolysis have also been reported.

Mechanism:

Immediate hypersensitivity reactions: Non–dose-related; likely immunologic (ie, IgE mediated, with specific antibodies formed against a drug allergen following initial exposure) or due to histamine-releasing activity (Ref). In addition, leuprolide appears to be a peptide ligand for MRGPRX2 receptor on mast cells and a cause for non-IgE–mediated mast cell activation (Ref).

Delayed hypersensitivity reactions: Non–dose-related; immunologic (involving a T-cell–mediated drug-specific immune response or immune complex-mediated) (Ref).

Granuloma: Non–dose-related; may be caused by a foreign-body reaction against polymers used as a vehicle for leuprolide injection or a reaction to leuprolide (Ref).

Onset:

Immediate hypersensitivity reactions: Rapid; generally occurs within 1 hour of administration but may occur up to 14 days after injection of the depot (Ref). Reactions have occurred with the first injection up to the 25th injection (Ref).

Delayed hypersensitivity reactions: Varied; typically occur days to 6 weeks after drug exposure (Ref).

Granulomas: Delayed; usually appear weeks to months after injection (Ref).

Risk factors:

• Cross-reactivity with other gonadotropin-releasing hormone analogues, including triptorelin and goserelin, may occur (Ref)

• Leuprolide acetate depot contains both carboxymethylcellulose (carmellose in Australia/Asia, E466 in Europe) and polysorbate 80, which are excipients that have independently been associated with anaphylaxis (Ref)

Metabolic changes/cardiovascular effects

Metabolic changes with androgen deprivation therapy (ADT) are concerning due to increased risk of both arterial and venous thromboembolic events (Ref). Gonadotropin releasing hormone (GnRH) agonists, such as leuprolide, may increase risk of a major cardiovascular and cerebrovascular event (20%) vs GnRH antagonists (3%) (Ref). Additionally, ischemic heart disease was found to be the most common cardiac disorder in a phase 3 randomized clinical trial with an incidence of 10% (Ref).

Mechanism: Dose-related; ADT decreases testosterone levels which elicits metabolic changes, such as decreased lean muscle mass, increased visceral fat, insulin resistance, and dyslipidemia, leading to a prothrombotic state that expedites atherosclerosis (Ref). Immunomodulatory changes, such as activation of atherosclerotic plaque T-cell GnRH receptors leading to plaque destabilization, are also being explored (Ref).

Onset: Delayed; risk increases during the first 6 months of ADT (Ref).

Risk factors:

• Duration of therapy (Ref)

• Prior cardiovascular disease/event or preexisting risk factors (Ref)

• Age ≥65 years (Ref)

Pituitary apoplexy

Gonadotropin-releasing hormone (GnRH) analogues have rarely been associated with pituitary apoplexy (Ref). Presentation is generally a sudden severe headache associated with visual impairment (photophobia, diplopia, or blurry vision), headache, vomiting, hyponatremia, and ophthalmoplegia (Ref). Immediate care ranging from medical management to surgical invention may be required (Ref).

Mechanism: Dose related; pituitary stimulation to underlying adenoma causes ischemic necrosis and subsequent hemorrhage, or compression of vessels may lead to infarction in the nonadenomatous gland (Ref).

Onset: Varied; most commonly occurs within hours (<4 hours) of first administration; has also been observed up to 14 days after administration (Ref).

Risk factors:

• Elderly males with underlying gonadotropin-secreting adenoma (Ref)

• Presence of pituitary macroadenoma (Ref)

Psychiatric events

Leuprolide has rarely been associated with acute mania and psychiatric signs and symptoms (Ref). There are very few case reports in the literature; however, the development of such events can require hospitalization and initiation of antidepressants and/or neuroleptic medications (Ref). Presentation is more common in those without prior history of psychiatric events, but exacerbations of existing pathology have been reported (Ref). In 23% of women taking a gonadotropin-releasing hormone agonist, depression was reported (Ref).

Mechanism: Unknown; however, estrogen withdrawal or deficit in central serotonin transmission is postulated (Ref).

Onset: Dose- and time-related; symptoms appear after several injections have been received (Ref).

QT prolongation

Cardiac arrhythmias associated with leuprolide therapy are very rare with incidence limited to clinical trials until a recent case report of prolonged QT interval on ECG and torsades de pointes (TdP) (Ref). In a phase 3 randomized clinical trial, supraventricular arrhythmias occurred in 4% of patients and prolonged QT interval occurred in 1% of patients (Ref).

Risk factors: Drug-induced QTc prolongation/TdP (in general):

• Females (Ref)

• Age >65 years (Ref)

• Structural heart disease (eg, history of myocardial infarction or heart failure with reduced ejection fraction) (Ref)

• Genetic defects of cardiac ion channels (Ref)

• History of drug-induced TdP (Ref)

• Congenital long QT syndrome (Ref)

• Baseline QTc interval prolongation (eg, >500 msec) or lengthening of the QTc by ≥60 msec (Ref)

• Electrolyte disturbances (eg, hypocalcemia, hypokalemia, hypomagnesemia) (Ref)

• Bradycardia (Ref)

• Hepatic impairment (Ref)

• Kidney impairment (Ref)

• Loop diuretic use (Ref)

• Sepsis (Ref)

• Concurrent administration of multiple medications (≥2) that prolong the QT interval or medications with drug interactions that increase serum concentrations of QT-prolonging medications (Ref)

Seizures

There are postmarketing reports of seizures with the use of long-acting leuprolide (Ref). While most seizures are classified as unspecified, cases of generalized, partial, and absence seizures are noted (Ref). Reports were mostly in females (average age 25 years) receiving therapy for endometriosis (Ref). There are 2 reports of seizure in pediatric patients with preexisting brain damage; resolution of seizure activity occurred with discontinuation of leuprolide therapy and initiation of treatment (Ref).

Mechanism: Postulated to be dose-related; related to pharmacological action. Potentially same mechanism as catamenial seizures since leuprolide causes transient increase in hormones (Ref).

Onset: Delayed; average onset is 41 days (Ref)

Risk factors:

• History of catamenial seizures (Ref)

• Preexisting brain damage (Ref)

Tumor flare

A tumor flare or transient increase in prostate cancer symptoms, especially in patients with advanced disease, presents as an exacerbation of initial symptoms, such as ureteral obstruction, urinary retention, spinal cord compression, and/or lymphedema (Ref). Sudden death during tumor flare has been reported (Ref). At one time, the incidence was estimated to be as high as 11%; however, advances in screening, earlier treatment, and the concurrent use of antiandrogen therapy have decreased the rate of tumor flare (Ref).

Mechanism: An initial increase in testosterone peaks ~3 days after administration, exacerbating symptoms (Ref).

Onset: Intermediate; symptoms observed within the first 1 to 3 weeks of receiving leuprolide (Ref).

Risk factors:

• Advanced disease (Ref)

• High prostate-specific antigen levels (Ref)

• Impending cord compression (Ref)

• Urethral obstruction (Ref)

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults, unless otherwise indicated.

>10%:

Cardiovascular: ECG changes (≤19%), edema (5% to 21%), flushing (children: 5%; adults: ≤78%), hypertension (children, adults: ≤15%), ischemia (≤19%) (table 1), peripheral edema (children, adults: ≤12%)

Leuprolide: Adverse Reaction: Ischemia

Drug (Leuprolide)

Comparator (Diethylstilbestrol)

Population

Dose

Dosage Form

Indication

Number of Patients (Leuprolide)

Number of Patients (Diethylstilbestrol)

Comments

19%

22%

Adult males

1 mg/day

SUBQ injection

Prostate cancer

98

101

Described as "ECG changes/ischemia"

Dermatologic: Diaphoresis (≤98%), pruritus (children: 11%; adults: 2% to 3%)

Endocrine & metabolic: Decreased libido (3% to 11%), hot flash (≤98%), increased serum cholesterol (23%), increased serum triglycerides (12% to 32%), weight gain (children, adults: ≤13%), weight loss (≤13%)

Gastrointestinal: Abdominal pain (children: 9% to 18%; adults: <1%), constipation (children: 6%; adults: ≤14%), diarrhea (children, adults: ≤16%), hematochezia (children: ≤13%), nausea (children: ≤13%; adults: ≤25%), vomiting (children: ≤13%; adults: ≤25%)

Genitourinary: Testicular atrophy (4% to 20%), vaginitis (children: ≤3%; adults: 11% to 28%)

Hematologic & oncologic: Bruise (children: ≤13%)

Local: Bruising at injection site (children: ≤78%; adults: 3% to 12%), discomfort at injection site (children: ≤78%; adults: ≤19%), erythema at injection site (children: ≤78%; adults: 2% to 38%), injection-site reaction (children: ≤78%; adults: ≤14%, including abscess at injection site), pain at injection site (children: ≤78%; adults: ≤19%), swelling at injection site (children: ≤78%), warm sensation at injection site (children: ≤78%)

Nervous system: Asthenia (children: <1%; adults: ≤18%), depression (children: ≤22%; adults: ≤31%) (table 2), dizziness (children: <1%; adults: ≤16%), emotional lability (children: ≤22%; adults: ≤31%), fatigue (≤18%), headache (children: 2% to 33%; adults: ≤65%), insomnia (children, adults: ≤31%), lethargy (≤13%), malaise (≤18%), migraine (≤65%), mood changes (children: ≤22%; adults: ≤5%), pain (3% to 33%), psychiatric signs and symptoms (children: ≤22%, including affective disorder, aggressive behavior, auditory hallucinations, crying, disruptive mood dysregulation disorder, trichotillomania), sleep disorder (≤31%), vertigo (≤16%)

Leuprolide: Adverse Reaction: Depression

Drug (Leuprolide)

Comparator (Danazol)

Placebo

Dosage Form

Indication

Number of Patients (Leuprolide)

Number of Patients (Danazol)

Number of Patients (Placebo)

Comments

22%

N/A

N/A

40 mg IM injection

Central precocious puberty in children

45

N/A

N/A

Described as “psychiatric event including depression”

31%

N/A

N/A

3.75 mg IM injection

Endometriosis in adults

51

N/A

N/A

Described as "depression/emotional lability"

22%

20%

3%

3.75 mg IM injection

Endometriosis in adults

166

136

31

Described as "depression/emotional lability"

11%

N/A

4%

3.75 mg IM injection

Uterine fibroids in adults

166

N/A

163

Described as "depression/emotional lability"

Neuromuscular & skeletal: Arthropathy (children: <2%; adults: 4% to 16%), increased creatinine phosphokinase in blood specimen, musculoskeletal pain (children: <1%; adults: ≤11%)

Respiratory: Cough (children, adults: 1% to 13%), epistaxis (children, adults: ≤13%), flu-like symptoms (children: <2%; adults: ≤21%), nasopharyngitis (children, adults: ≤22%), upper respiratory tract infection (children: 6%; adults: ≤21%)

Miscellaneous: Fever (children: 13% to 17%; adult: <5%)

1% to 10%:

Cardiovascular: Acute myocardial infarction (<5%), angina pectoris (<5%), atrial fibrillation (<5%), bradycardia (children, adults: <5%), cardiac arrhythmia (<5%), chest pain (children: 4%), coronary artery disease (≤6%), deep vein thrombophlebitis (<5%), heart failure (1%), heart murmur (3%), hypotension (children; adults: <5%), palpitations (<5%), peripheral vascular disease (<2%), phlebitis (≤2%), pitting edema (≤5%), syncope (children, adults: <5%), tachycardia (<5%), thrombosis (≤2%), varicose veins (<5%), vasodilation (children: 2%)

Dermatologic: Acne vulgaris (children: ≤3%; adults: ≤10%), allergic skin reaction (≤10%), alopecia (children, adults: ≤4%), body odor (children, adults: <5%), cellulitis (<5%), cold and clammy skin (4%), dermatitis (5%), ecchymoses (<5%), erythema multiforme (children: ≤3%), hair disease (<5%), hyperhidrosis (children: 4%), hyperpigmentation (including dyschromia: <5%), leukoderma (children: <2%), malignant melanoma, nail disease (children, adults: <5%), night sweats (3%), seborrhea (children: ≤3%), skin carcinoma (including ear: <5%), skin hypertrophy (children: <2%), skin lesion (<5%), skin rash (children, adults: 7%), xeroderma (<5%)

Endocrine & metabolic: Androgen-like effect (females: ≤4%), decreased HDL cholesterol (2% to 10%), decreased serum albumin (≥5%), decreased serum bicarbonate (≥5%), decreased serum total protein (≥5%), dehydration (8%), diabetes mellitus (children; adults: <5%), feminization (children: <2%), goiter (children, adults: <5%), growth retardation (children: <2%), gynecomastia (children, adults: ≤7%), hirsutism (children: <2%), hyperglycemia (≥5%), hyperphosphatemia (≥5%), hyperuricemia (≥5%), hypoglycemia (<5%), increased lactate dehydrogenase (≥5%), increased LDL cholesterol (8%), increased serum calcium (<5%), increased thirst (<5%), increased uric acid (≥5%), loss of libido (<2%), menstrual disease (children, adults: ≤2%)

Gastrointestinal: Abdominal distention (<5%), anorexia (6%), change in appetite (4%), colitis (≤3%), duodenal ulcer (<5%), dysgeusia (<5%), dyspepsia (children, adults: <4%), dysphagia (children, adults: <5%), eructation (<5%), flatulence (≤4%), gastroenteritis (≤3%), gastrointestinal hemorrhage (<5%), gingival hemorrhage (<5%), gingivitis (children, adults: <5%), hernia of abdominal cavity (<5%), hiccups (<5%), increased appetite (children, adults: <5%), intestinal obstruction (<5%), melanosis (<5%), mucous membrane abnormality (reaction: ≤4%), peptic ulcer (<5%), periodontal abscess (<5%), rectal polyp (<5%), xerostomia (<5%)

Genitourinary: Balanitis (<5%), bladder carcinoma (<5%), bladder spasm (<5%), breast changes (≤6%), breast disease (children: <2%), breast hypertrophy (children; adults: <5%), breast tenderness (children, adults: ≤7%), cervical neoplasm (children: <2%), cervix disease (children: <2%), decreased prostatic acid phosphatase (≥5%), difficulty in micturition (<2%), dysmenorrhea (children: <2%), dysuria (≤6%), epididymitis (<5%), erectile dysfunction (4% to 5%), hematuria (≤6%), hemorrhagic cystitis (including cystitis: ≤6%), increased prostatic acid phosphatase (≥5%), lactation (<5%), mastalgia (≤7%), nocturia (1% to 6%), oliguria (<2%), penile disease (<5%), pollakiuria (2%), prostatic disease (<5%), reduction in penile size (<2%), sexual disorder (accelerated sexual maturity: children: <2%), testicular disease (<5%), testicular pain (2%), urinary frequency (≤6%), urinary incontinence (children, adults: <5%), urinary retention (<2%), urinary tract infection (≤6%), urinary tract obstruction (<5%), urinary tract pain (1%), urinary urgency (≤6%), vaginal discharge (children: ≤3%), vaginal hemorrhage (children: ≤3%)

Hematologic & oncologic: Anemia (≤6%), carcinoma (<5%), eosinophilia (≥5%), increased erythrocyte sedimentation rate (children: <2%), leukopenia (≥5%), lymphadenopathy (<5%), lymphedema (<5%), neoplasm (<5%), prolonged partial thromboplastin time (≥5%), prolonged prothrombin time (≥5%), purpuric disease (children: <2%), second primary malignant neoplasm (including basal cell carcinoma of skin, malignant melanoma, non-Hodgkin lymphoma, pulmonary neoplasm), squamous cell carcinoma (7%), thrombocytosis (≥5%), tumor flare (children: <2%)

Hepatic: Abnormal hepatic function tests (≥5%), hepatomegaly (<5%), increased gamma-glutamyl transferase (≥5%), increased serum alanine aminotransferase (≥5%), increased serum aspartate aminotransferase (≥5%), increased serum transaminases (3%)

Hypersensitivity: Hypersensitivity reaction (children, adults: <5%)

Immunologic: Increased ANA titer (children: <2%)

Infection: Abscess (<5%), herpes zoster infection (<5%), infection (children, adults: ≤5%)

Local: Induration at injection site (children, adults: <3%), injection-site pruritus (≤9%)

Nervous system: Abnormality in thinking (<5%), agitation (<5%), altered sense of smell (<2%), amnesia (<5%), anxiety (≤8%), chills (<5%), confusion (<5%), delusion (<5%), dementia (<5%), drowsiness (children: <2%), hypoesthesia (<5%), irritability (including impatience: 2%), loss of consciousness (<5%), memory impairment (6%), nervousness (children: <2%; adults: ≤8%), neuropathy (<5%), numbness (<5%), paralysis (children; adults: <5%), paresthesia (≤8%), peripheral neuropathy (children; adults: <5%), personality disorder (<5%), rigors (<2%), tremor (<2%), voice disorder (<5%)

Neuromuscular & skeletal: Amyotrophy (<2%), arthralgia (children: <2%; adults: ≤9%), arthritis (≤1%), back pain (children, adults: ≤7%), bone disease (temporal bone swelling: <5%), hyperkinetic muscle activity (children: <2%), limb pain (children, adults: ≤10%), lower limb cramp (≤2%), myalgia (can be severe: children: <2%; adults: ≤8%), myopathy (children: <2%), neck pain (<5%), ostealgia (2% to 5%), pathological fracture (children, adults: <5%)

Ophthalmic: Amblyopia (<5%), blepharoptosis (<5%), blurred vision (<5%), conjunctivitis (<5%), dry eye syndrome (<5%), visual disturbance (children, adults: <5%)

Otic: Tinnitus (<5%)

Renal: Decreased urine specific gravity (≥5%), increased blood urea nitrogen, increased serum creatinine, increased urine specific gravity (≥5%)

Respiratory: Asthma (children, adults: <5%), bronchitis (<5%), bronchospasm (children: 6%), chronic obstructive pulmonary disease (5%), dyspnea (≤5%), dyspnea on exertion (1% to 5%), hemoptysis (<5%), hypoxia (<5%), increased bronchial secretions (<5%), paranasal sinus congestion (5%), pharyngitis (children, adults: <5%), pleural effusion (<5%), pleural rub (<5%), pneumonia (<5%), productive cough (children: 6%), pulmonary edema (<5%), pulmonary emphysema (<5%), pulmonary fibrosis (<5%), rhinitis (children, adults: <5%), sinus headache (≤8%), sinusitis (children, adults: <5%)

Miscellaneous: Abnormal healing (<5%), cyst (<5%), inflammation (<5%)

<1%:

Dermatologic: Pallor (children)

Endocrine & metabolic: Obesity (children)

Gastrointestinal: Abdominal distress, decreased appetite (children)

Genitourinary: Exacerbation of hematuria

Local: Hematoma at injection site (children)

Nervous system: Abnormal gait (children)

Frequency not defined (all populations):

Cardiovascular: Aortic aneurysm (ruptured), carotid stenosis, chest tightness, extrasystoles

Dermatologic: Hyperkeratosis, spider telangiectasia

Endocrine & metabolic: Decreased serum potassium, galactorrhea not associated with childbirth (females), hyperkalemia, increased libido, increased testosterone level, pituitary insufficiency (suppression of pituitary-gonadal system), thyroid nodule

Gastrointestinal: Occult blood in stools, rectal fistula, rectal irritation (erythema)

Genitourinary: Blisters on penis, increased post-void residual urine volume, penile swelling, pyuria, ureteral obstruction

Hematologic & oncologic: Hypoproteinemia, leukocytosis, thrombocytopenia

Hepatic: Hepatitis

Hypersensitivity: Facial edema, facial swelling

Local: Burning sensation at injection site (including stinging), skin ulceration at injection site

Nervous system: Anosmia, burning sensation of feet, cerebrovascular accident, euphoria, hyperreflexia, hyporeflexia, motor dysfunction, spinal cord compression, transient ischemic attacks

Neuromuscular & skeletal: Ankylosing spondylitis, knee effusion, muscle cramps, muscle rigidity, muscle tenderness

Ophthalmic: Eyelid edema, retinal vascular disease (perivascular cuffing)

Otic: Auditory disturbance (including decreased hearing)

Renal: Nephrolithiasis, pyelonephritis

Respiratory: Abnormal breath sounds (decreased), dry throat, pleuritic chest pain, pulmonary infiltrates, rales, rhonchi, streptococcal pharyngitis, wheezing

Miscellaneous: Fibrosis (pelvic), mass

Postmarketing (all populations):

Cardiovascular: Deep vein thrombosis, prolonged QT interval on ECG (Abbasi 2020), pulmonary embolism, torsades de pointes (Abbasi 2020)

Dermatologic: Acute generalized exanthematous pustulosis, bullous dermatitis, exfoliative dermatitis, hypertrichosis, skin photosensitivity, Stevens-Johnson syndrome, toxic epidermal necrolysis, urticaria (Okdemir 2015)

Endocrine & metabolic: Diabetes mellitus with hyperosmolar coma (Saad 2022), pituitary apoplexy (Fabiano 2016; Tanios 2017)

Genitourinary: Prostate pain

Hematologic & oncologic: Adenoma (pituitary), decreased white blood cell count

Hepatic: Acute hepatotoxicity, hepatic impairment, liver steatosis, severe hepatotoxicity

Hypersensitivity: Anaphylaxis (Fujisaki 2012), angioedema (Kirkgoz 2020), drug reaction with eosinophilia and systemic symptoms, hypersensitivity angiitis (Gnanaraj 2010), nonimmune anaphylaxis, serum sickness (Gnanaraj 2010)

Local: Injection site granuloma (Yasukawa 2005)

Nervous system: Fibromyalgia syndrome, intracranial hypertension (including idiopathic intracranial hypertension) (Tan 2019), mania (Pong 2014), outbursts of anger (Chavez 2010), seizure (Akaboshi 2000), suicidal ideation, suicidal tendencies

Neuromuscular & skeletal: Bone fracture (including spinal) (Shahinian 2005), decreased bone mineral density (Dawood 1995; Kaya 2015; Smith 2006), muscle spasm, slipped capital femoral epiphysis, tenosynovitis (symptoms)

Respiratory: Interstitial lung disease (interstitial pneumonitis) (Villalba-Cuesta 2022)

Miscellaneous: Nodule (throat)

Contraindications

Hypersensitivity to leuprolide, GnRH, GnRH-agonist analogs, or any component of the formulation.

Fensolvi, Lupron-Depot-Ped: Additional contraindications: pregnancy.

Lupron Depot 3.75 mg (monthly) and Lupron Depot 11.25 mg (3-month): Additional contraindications: patients with undiagnosed uterine bleeding; pregnancy.

Canadian labeling: Additional contraindications (not in US labeling): Patients who are or who could become pregnant; breastfeeding. Zeulide Depot (Canadian product) is also contraindicated in females.

Warnings/Precautions

Concerns related to adverse effects:

• Metabolic syndrome: Metabolic changes (such as hyperglycemia, diabetes, hyperlipidemia) may occur; metabolic dysfunction–associated steatotic liver disease, including cirrhosis, has also been reported. Hyperglycemia may manifest as new-onset diabetes or worsening of glycemic control in patients with preexisting diabetes.

• Pseudotumor cerebri: Pseudotumor cerebri (idiopathic intracranial hypertension) has been reported in pediatric patients receiving GnRH agonists, including leuprolide acetate, but is very rare (Omar 2020).

Disease-related concerns:

• Asthma: Asthma exacerbations have been reported with therapy in patients with histories of asthma, sinusitis, or environmental or drug allergies.

• Central precocious puberty: Children treated for precocious puberty may experience signs and symptoms of puberty, including vaginal bleeding, during the first weeks of treatment or after subsequent doses due to the initial stimulatory effect of leuprolide before suppression occurs; health care provider should be notified if symptoms continue after the second month.

• Depression: Monitor for new or worsening depression, especially in patients with a history of depression.

• Endometriosis: Due to the physiologic effects of the drug, exacerbation of endometriosis symptoms may occur after the first dose of leuprolide.

Dosage form specific issues:

• Benzyl alcohol and derivatives: Some dosage forms may contain benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC 1982); some data suggest that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol with caution in neonates. See manufacturer's labeling.

• Depot formulations: Vehicle used in injectable (polylactide-co-glycolide microspheres) has rarely been associated with retinal artery occlusion in patients with abnormal arteriovenous anastomosis (eg, patent foramen ovale) (Tang 2007). Do not use a fractional dose of the 3-, 4-, or 6-month depot formulation, or a combination of doses of the monthly depot formulation or any depot formulation due to different release characteristics. The Atrigel delivery system (used in Eligard/Fensolvi) is a nongelatin-based, biodegradable, polymer matrix.

• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer's labeling.

Other warnings/precautions:

• Appropriate use: For the treatment of endometriosis, leuprolide can be used in combination with norethindrone acetate (referred to as add-back therapy) to reduce bone mineral density loss and reduce vasomotor symptoms associated with use of leuprolide acetate. Leuprolide in combination with norethindrone acetate (add-back therapy) is not indicated for the preoperative hematologic improvement of patients with anemia caused by heavy menstrual bleeding due to uterine fibroids.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Injectable, Intramuscular, as acetate:

Generic: 22.5 mg (1 ea)

Kit, Injection, as acetate:

Generic: 1 mg/0.2 mL

Kit, Intramuscular, as acetate:

Lupron Depot (1-Month): 7.5 mg [latex free; contains polysorbate 80]

Lupron Depot (6-Month): 45 mg [latex free; contains polysorbate 80]

Lupron Depot-Ped (6-Month): 45 mg [latex free; contains polysorbate 80]

Kit, Intramuscular, as acetate [preservative free]:

Lupron Depot (1-Month): 3.75 mg [latex free; contains polysorbate 80]

Lupron Depot (3-Month): 11.25 mg, 22.5 mg [latex free; contains polysorbate 80]

Lupron Depot (4-Month): 30 mg [latex free; contains polysorbate 80]

Lupron Depot-Ped (1-Month): 7.5 mg, 11.25 mg, 15 mg [latex free; contains polysorbate 80]

Lupron Depot-Ped (3-Month): 30 mg (Ped), 11.25 mg (Ped) [latex free; contains polysorbate 80]

Kit, Subcutaneous, as acetate:

Eligard: 7.5 mg

Eligard: 7.5 mg, 22.5 mg, 30 mg, 45 mg [contains methylpyrrolidone, polylactide-coglycolide]

Fensolvi (6 Month): 45 mg

Fensolvi (6 Month): 45 mg [contains methylpyrrolidone, polylactide-coglycolide]

Kit, Subcutaneous, as acetate [preservative free]:

Eligard: 30 mg [contains methylpyrrolidone, polylactide-coglycolide]

Prefilled Syringe, Subcutaneous, as mesylate [preservative free]:

Camcevi: 42 mg (1 ea) [latex free]

Generic Equivalent Available: US

May be product dependent

Pricing: US

Injection (Leuprolide Acetate (3 Month) Intramuscular)

22.5 mg (per each): $1,626.08

Kit (Eligard Subcutaneous)

7.5 mg (per each): $542.03

22.5 mg (per each): $1,626.08

30 mg (per each): $2,168.11

45 mg (per each): $3,252.16

Kit (Fensolvi (6 Month) Subcutaneous)

45 mg (per each): $31,363.51

Kit (Leuprolide Acetate Injection)

1 mg/0.2 mL (per each): $808.80 - $891.00

Kit (Lupron Depot (1-Month) Intramuscular)

3.75 mg (per each): $2,058.41

7.5 mg (per each): $2,452.92

Kit (Lupron Depot (3-Month) Intramuscular)

11.25 mg (per each): $6,175.28

22.5 mg (per each): $7,358.72

Kit (Lupron Depot (4-Month) Intramuscular)

30 mg (per each): $9,811.66

Kit (Lupron Depot (6-Month) Intramuscular)

45 mg (per each): $14,717.70

Kit (Lupron Depot-Ped (1-Month) Intramuscular)

7.5 mg (per each): $2,476.28

11.25 mg (per each): $4,495.63

15 mg (per each): $4,951.49

Kit (Lupron Depot-Ped (3-Month) Intramuscular)

11.25 mg (per each): $13,486.94

30 mg (per each): $14,854.52

Kit (Lupron Depot-Ped (6-Month) Intramuscular)

45 mg (per each): $29,709.02

Prefilled Syringe (Camcevi Subcutaneous)

42 mg (per each): $5,124.08

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Injectable, Intramuscular:

Lupron Depot: 30 mg (1 ea) [contains polysorbate 80]

Kit, Intramuscular, as acetate:

Lupron Depot (1-Month): 3.75 mg, 7.5 mg [contains polysorbate 80]

Lupron Depot (3-Month): 11.25 mg [contains polysorbate 80]

Lupron Depot 3 Month Kit: 22.5 mg [contains polysorbate 80]

Zeulide Depot: 3.75 mg, 22.5 mg [contains polysorbate 80]

Kit, Subcutaneous, as acetate:

Eligard: 7.5 mg, 22.5 mg, 30 mg, 45 mg

Solution, Subcutaneous:

Lupron: 1 mg/0.2 mL ([DSC]) [contains benzyl alcohol]

Administration: Adult

Do not use a fractional dose of the 3-, 4-, or 6-month depot formulation, or a combination of doses of the monthly depot formulation or any depot formulation due to different release characteristics. Do not use a combination of syringes to achieve a particular dose. Do not administer IV.

IM:

Leuprolide Depot (generic, Cipla): Administer as a single injection into the gluteal area, anterior thigh, or deltoid. Injection site should be alternated. Administer immediately after preparation.

Lupron Depot: Must be administered by a health care provider. Administer as a single injection into the gluteal area, anterior thigh, or deltoid. Injection site should be alternated. Administer within 2 hours of preparation.

Zeulide Depot [Canadian product]: Allow product to reach room temperature before administration. Inject into the upper outer quadrant of the gluteus.

SUBQ:

Camcevi: Select an injection site in the upper or mid abdominal area with sufficient soft or loose SUBQ tissue that has not been used recently; do not administer into areas with brawny or fibrous SUBQ tissue or locations that could be rubbed or compressed (eg, belt or waistband). Bunch skin around injection site, insert needle at a 90-degree angle to the skin surface, release skin, and slowly and steadily inject full contents; remove needle at the same 90-degree angle. Avoid applying heat directly to the injection site.

Eligard: Vary/rotate injection site; choose site with adequate subcutaneous tissue (eg, upper or mid-abdomen, upper buttocks) that does not have excessive pigment, nodules, lesions, or hair. Avoid areas with brawny or fibrous tissues or areas that may be compressed or rubbed (eg, belt or waistband). Administer within 30 minutes of preparation.

Leuprolide acetate 5 mg/mL solution (1 mg/0.2 mL): Vary injection site; if an alternate syringe from the syringe provided is required, insulin syringes should be used.

Administration: Pediatric

Parenteral: Note: Do not use a fractional dose of the 3-, 4-, or 6-month depot formulation, or a combination of doses of the monthly depot formulation or any depot formulation due to different release characteristics. Do not use a combination of syringes to achieve a particular dose. Do not administer IV.

IM: Lupron Depot, Lupron Depot-Ped: Administer as a single injection into the gluteal area, anterior thigh, or deltoid; rotate administration site periodically. Reconstituted solution does not contain preservatives and should be used immediately. Lupron Depot-Ped should be administered by a health care professional.

SUBQ:

Long-acting formulation: Fensolvi: Should be administered by a health care professional. Administer as a single SUBQ injection into the abdomen, upper buttocks, or other location with adequate SUBQ tissue that does not have excessive pigment, nodules, lesions, or hair. Avoid areas for injection with brawny or fibrous SUBQ tissue or areas of skin that may be rubbed or compressed (belts or clothing waistband). Rotate injection sites.

Short-acting formulation: Leuprolide acetate 5 mg/mL solution: Administer undiluted into areas on the arm, thigh, or abdomen; rotate injection site. If an alternate syringe from the manufacturer-provided syringe is required, insulin syringes should be used.

Hazardous Drugs Handling Considerations

Hazardous agent (NIOSH 2016 [group 1]).

Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).

Medication Guide and/or Vaccine Information Statement (VIS)

An FDA-approved patient medication guide, which is available with the product information, and as follows, must be dispensed with this medication:

Fensolvi: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/213150s002lbl.pdf#page=15

Lupron Injection: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/019010s038lbl.pdf#page=27

Lupron Depot-Ped: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/020263s053lbl.pdf#page=26

Use: Labeled Indications

Central precocious puberty: Treatment of pediatric patients with central precocious puberty.

Endometriosis: For use in the management of endometriosis, either as monotherapy (for pain relief and reduction of endometriotic lesions) or as combination therapy with norethindrone acetate (for the initial management of the painful symptoms of endometriosis and management of symptom recurrence).

Limitations of use: Not for use prior to menarche or post-menopause. Monotherapy is not recommended for retreatment.

Prostate cancer, advanced: Treatment of advanced prostate cancer.

Uterine leiomyomata (fibroids): For use in combination with iron for the preoperative hematologic improvement of patients with anemia caused by fibroids when 3 months of hormonal suppression is deemed necessary.

Limitations of use: Not for use prior to menarche or post-menopause. Leuprolide acetate is not indicated for combination use with norethindrone acetate for the preoperative hematologic improvement of patients with anemia caused by heavy menstrual bleeding due to fibroids.

Use: Off-Label: Adult

Breast cancer, premenopausal ovarian suppression for fertility preservation during chemotherapy; Breast cancer, premenopausal ovarian suppression during endocrine therapy; Breast cancer in male patients, hormone receptor–positive; Hormone therapy for transgender females (assigned male at birth); Paraphilia, males

Medication Safety Issues
Sound-alike/look-alike issues:

Lupron Depot (1-month, 3-month, or 6-month formulation) may be confused with Lupron Depot-Ped (1-month, 3-month, or 6-month formulation).

Lupron Depot-Ped is available in three formulations, a 1-month formulation, a 3-month formulation, and a 6-month formulation. Both the 1-month and 3-month formulations offer an 11.25 mg strength, which may further add confusion.

High alert medication:

The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs (chemotherapeutic agent, parenteral and oral; contraindicated in pregnancy [Fensolvi, Lupron Depot]) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Acute Care and Community/Ambulatory Care Settings).

Other safety concerns:

Leuprolide is available as different salt formulations (leuprolide acetate and leuprolide mesylate). Use caution when selecting a leuprolide formulation, as indications and dosing vary between the products.

Metabolism/Transport Effects

None known.

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.

Antidiabetic Agents: Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy

Choline C 11: Luteinizing Hormone-Releasing Hormone Analogs may diminish the therapeutic effect of Choline C 11. Risk C: Monitor therapy

Corifollitropin Alfa: Luteinizing Hormone-Releasing Hormone Analogs may enhance the therapeutic effect of Corifollitropin Alfa. Risk X: Avoid combination

Flotufolastat F18: Androgen Deprivation Therapy Agents may diminish the diagnostic effect of Flotufolastat F18. Management: Androgen deprivation therapy (ADT) may result in changes in the uptake of flotufolastat F18 in prostate cancer. The impact of ADT on the performance of flotufolastat F18 is unknown, but use of alternative agents should be considered. Risk D: Consider therapy modification

Gallium Ga 68 PSMA-11: Androgen Deprivation Therapy Agents may diminish the therapeutic effect of Gallium Ga 68 PSMA-11. Management: Androgen deprivation therapy (ADT) may result in changes in the uptake of gallium Ga 68 PSMA-11 (gozetotide) in prostate cancer. The impact of ADT on the performance of gallium Ga 68 PSMA-11 is unknown, but use of alternative agents should be considered. Risk D: Consider therapy modification

Haloperidol: QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of Haloperidol. Risk C: Monitor therapy

Indium 111 Capromab Pendetide: Luteinizing Hormone-Releasing Hormone Analogs may diminish the diagnostic effect of Indium 111 Capromab Pendetide. Risk X: Avoid combination

Piflufolastat F18: Androgen Deprivation Therapy Agents may diminish the diagnostic effect of Piflufolastat F18. Management: Androgen deprivation therapy (ADT) may result in changes in the uptake of piflufolastat F18 in prostate cancer. The impact of ADT on the performance of piflufolastat F18 is unknown, but use of alternative agents should be considered. Risk D: Consider therapy modification

QT-prolonging Agents (Highest Risk): QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

Reproductive Considerations

Evaluate pregnancy status prior to use and throughout treatment in patients who could become pregnant; pregnancy should be excluded prior to use.

Treatment with leuprolide usually inhibits ovulation and stops menstruation; however, contraception is not ensured. When contraception is indicated, a nonhormonal contraceptive should be used during leuprolide therapy.

Leuprolide suppresses ovarian and testicular steroidogenesis. Decreased libido, impotence, erectile dysfunction, and menstrual disorders may result and fertility may be impaired. Suppression of fertility is reversible following discontinuation of leuprolide. Pregnancy rates are not expected to be affected once leuprolide is discontinued. When used to treat pain associated with endometriosis in patients who are infertile, fertility is not improved by leuprolide treatment (ASRM 2012).

Leuprolide is used off label to suppress menstruation and preserve ovarian function and fertility in patients undergoing chemotherapy; however, leuprolide is not considered to be an effective contraceptive; a nonhormonal contraceptive is recommended when leuprolide is used during chemotherapy (ACOG 2018; ACOG 2021).

Pregnancy Considerations

Based on the mechanism of action and data from animal reproduction studies, in utero exposure to leuprolide may cause fetal harm. Use is contraindicated during pregnancy.

Breastfeeding Considerations

It is not known if leuprolide is present in breast milk.

According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother.

Monitoring Parameters

Monitor bone mineral density. Monitor for signs/symptoms of hypersensitivity (including delayed hypersensitivity), severe cutaneous adverse reactions (including Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms, and acute generalized exanthematous pustulosis), and pseudotumor cerebri. Monitor for development or worsening of psychiatric symptoms. Evaluate pregnancy status in patients who could become pregnant (prior to use and during therapy).

Endometriosis: Endometrial-related pain.

Paraphilia: CBC (baseline, monthly for 4 months then every 6 months); serum testosterone (baseline, monthly for 4 months then every 6 months); serum luteinizing hormone (LH) (baseline and every 6 months), follicle-stimulating hormone (FSH) (baseline), serum BUN and creatinine (baseline and every 6 months); bone density (baseline and yearly); ECG (baseline) (Reilly 2000).

Precocious puberty:

Response to treatment (GnRH agonist stimulation test, basal serum luteinizing hormone levels or serum sex steroid levels), height, bone age.

Prostate cancer: LH and FSH levels, serum testosterone (~4 weeks after initiation of therapy), prostate specific antigen. Screen for diabetes (monitor blood glucose and HbA1c; periodically and as clinically necessary), serum lipids, and cardiovascular risk prior to initiating and periodically during treatment. Consider periodic monitoring of electrocardiograms and electrolytes in patients at risk for QT prolongation. Monitor for signs/symptoms of emerging cardiovascular disease, tumor flare, urinary tract, and spinal cord compression (observe patients with metastatic vertebral lesions closely, particularly in the first few weeks of treatment).

Transgender hormone therapy: Serum testosterone levels (goal <50 ng/dL) every 3 months during the first year and then annually or biannually; serum LH, FSH, and prolactin levels at baseline and annually; routine cancer and laboratory screening as in non-transgender individuals for all tissues present (ES [Hembree 2017]; Gava 2016).

Cardiovascular monitoring for patients with prostate cancer: Comprehensive assessment prior to treatment including a history and physical examination, screening for cardiovascular disease risk factors such as hypertension, diabetes, dyslipidemia, obesity, and smoking; baseline and serial ECGs are recommended in patients at risk of QTc prolongation during androgen deprivation therapy (ADT); estimate 10-year cardiovascular disease risk in patients without cardiovascular disease at baseline; assess cardiovascular risk annually during ADT (ASCO [Armenian 2017]; ESC [Lyon 2022]).

Reference Range

Testosterone, castrate levels: ≤50 ng/dL (SI: ≤1.7 nmol/L).

Mechanism of Action

Leuprolide is an agonist of gonadotropin releasing hormone (GnRH) receptors. Acting as a potent inhibitor of gonadotropin secretion, leuprolide produces an initial increase in luteinizing hormone (LH) and follicle stimulating hormone (FSH), which leads to a transient increase (5 to 12 days [Cook 2000]) in testosterone and dihydrotestosterone (in males) and estrone and estradione (in premenopausal females). Continuous leuprolide administration then results in suppression of ovarian and testicular steroidogenesis due to decreased levels of LH and FSH with subsequent decrease in testosterone (male) and estrogen (female) levels. In males, testosterone levels are reduced to below castrate levels. Leuprolide may also have a direct inhibitory effect on the testes, and act by a different mechanism not directly related to reduction in serum testosterone.

Pharmacokinetics (Adult Data Unless Noted)

Onset of action: Following transient increase, testosterone suppression occurs in ~2 to 4 weeks of continued therapy.

Onset of therapeutic suppression for precocious puberty: Leuprolide: 2 to 4 weeks; Leuprolide depot: 1 month.

Distribution: Males: Vd: 27 L.

Protein binding: 43% to 49%.

Metabolism: Metabolized to smaller inactive peptides, then may be further catabolized; Major metabolite, pentapeptide (M-1).

Bioavailability: SUBQ: 94%.

Half-life elimination: ~3 hours.

Time to peak: Camcevi: 3.2 hours (first dose) and 2.1 hours (second dose); Eligard: ~5 hours (7.5 mg), ~3.3 hours (30 mg), or ~4.5 hours (45 mg).

Excretion: Urine (<5% as parent and major metabolite).

Clearance: Camcevi: 7.6 L/hour; Eligard: 8.34 L/hour.

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (AR) Argentina: Eligard;
  • (AU) Australia: Lucrin;
  • (BE) Belgium: Leuproreline sandoz;
  • (BR) Brazil: Lupron | Reliser;
  • (CH) Switzerland: Lucrin;
  • (CO) Colombia: Leuprolide acetato | Lupron;
  • (DE) Germany: Leupro sandoz | Leuprone HEXAL;
  • (EC) Ecuador: Lupron;
  • (EG) Egypt: Lucrin;
  • (ES) Spain: Procrin;
  • (FI) Finland: Procren;
  • (FR) France: Enantone | Lucrin;
  • (GB) United Kingdom: Staladex;
  • (GR) Greece: Daronda;
  • (HK) Hong Kong: Lucrin;
  • (IN) India: Agopride | Eurolide | Leuren | Lupride | Luprodex md | Luprofact | Luprorin | Progtase;
  • (IT) Italy: Enantone die;
  • (KR) Korea, Republic of: Lucrin;
  • (KW) Kuwait: Lucrin;
  • (MX) Mexico: Lucrin | Prelar;
  • (MY) Malaysia: Lucrin;
  • (NL) Netherlands: Leuproreline-Acetaat | Lucrin;
  • (NZ) New Zealand: Lucrin;
  • (PE) Peru: Lorelina depot | Lupron;
  • (PR) Puerto Rico: Eligard | Leuprolide ace | Leuprolide acetate | Lupron | Lupron depot | Lupron Depot-3 Month | Lupron Depot-4 Month;
  • (PT) Portugal: Leuprolide | Lucrin;
  • (QA) Qatar: Eligard 1 Month | Eligard 3 Month | Eligard 6 Month;
  • (SE) Sweden: Leuprorelin sandoz | Lupron | Procren;
  • (SG) Singapore: Lucrin;
  • (TR) Turkey: Lucrin | Prosalid;
  • (TW) Taiwan: Leuprolide acetate | Lupro | Lupron;
  • (UY) Uruguay: Lupron;
  • (VE) Venezuela, Bolivarian Republic of: Lupron;
  • (ZA) South Africa: Lucrin
  1. <800> Hazardous Drugs–Handling in Healthcare Settings. United States Pharmacopeia and National Formulary (USP 43-NF 38). Rockville, MD: United States Pharmacopeia Convention; 2020:74-92.
  2. Abbasi D, Faiek S, Shetty S, Khan E. Shock from twisting peaks: A rare case of recurrent torsades de pointes secondary to leuprolide-induced prolonged QT. Cureus. 2020;12(7):e9041. doi:10.7759/cureus.9041 [PubMed 32782861]
  3. Adjuvant Breast Cancer Trials Collaborative Group. Ovarian ablation or suppression in premenopausal early breast cancer: results from the international adjuvant breast cancer ovarian ablation or suppression randomized trial. J Natl Cancer Inst. 2007;99(7):516-525. doi:10.1093/jnci/djk109 [PubMed 17405996]
  4. Ahlfors CE. Benzyl alcohol, kernicterus, and unbound bilirubin. J Pediatr. 2001;139(2):317-319. doi:10.1067/mpd.2001.116281 [PubMed 11487763]
  5. Akaboshi S, Takeshita K. A case of atypical absence seizures induced by leuprolide acetate. Pediatr Neurol. 2000;23(3):266-268. doi:10.1016/s0887-8994(00)00181-8 [PubMed 11033292]
  6. Alade SL, Brown RE, Paquet A Jr. Polysorbate 80 and E-ferol toxicity. Pediatrics. 1986;77(4):593-597. [PubMed 3960626]
  7. American College of Obstetricians and Gynecologists’ (ACOG) Committee on Adolescent Health Care. Options for prevention and management of menstrual bleeding in adolescent patients undergoing cancer treatment: ACOG committee opinion, no. 817. Obstet Gynecol. 2021;137(1):e7-e15. doi:10.1097/AOG.0000000000004209 [PubMed 33399429]
  8. American College of Obstetricians and Gynecologists' (ACOG) committee opinion no. 760: dysmenorrhea and endometriosis in the adolescent. Obstet Gynecol. 2018 Dec;132(6):e249-e258. doi:10.1097/AOG.0000000000002978 [PubMed 30461694]
  9. Armenian SH, Lacchetti C, Barac A, et al. Prevention and monitoring of cardiac dysfunction in survivors of adult cancers: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol. 2017;35(8):893-911. doi:10.1200/JCO.2016.70.5400 [PubMed 27918725]
  10. Bhatia N, Santos M, Jones LW, et al. Cardiovascular effects of androgen deprivation therapy for the treatment of prostate cancer: ABCDE steps to reduce cardiovascular disease in patients with prostate cancer. Circulation. 2016;133(5):537-541. doi:10.1161/CIRCULATIONAHA.115.012519 [PubMed 26831435]
  11. Basch E, Loblaw DA, Oliver TK, et al. Systemic therapy in men with metastatic castration-resistant prostate cancer: American Society of Clinical Oncology and Cancer Care Ontario clinical practice guideline. J Clin Oncol. 201420;32(30):3436-3448. doi:10.1200/JCO.2013.54.8404 [PubMed 25199761]
  12. Bellón T. Mechanisms of severe cutaneous adverse reactions: Recent advances. Drug Saf. 2019;42(8):973-992. doi:10.1007/s40264-019-00825-2 [PubMed 31020549]
  13. Bernad DM, Dal Pra A, Baule C, Frey BN, Faria S. New-onset psychosis following androgen deprivation therapy for prostate cancer. Can J Urol. 2013;20(4):6868-68670. [PubMed 23930615]
  14. Blumenthal KG, Peter JG, Trubiano JA, Phillips EJ. Antibiotic allergy. Lancet. 2019;393(10167):183-198. doi:10.1016/S0140-6736(18)32218-9 [PubMed 30558872]
  15. Burris K, Ding CY, Lim GF. Leuprolide acetate-induced generalized papular eruption. J Drugs Dermatol. 2014;13(6):755-757. [PubMed 24918569]
  16. Burstein HJ, Lacchetti C, Anderson H, et al. Adjuvant endocrine therapy for women with hormone receptor-positive breast cancer: American Society of Clinical Oncology clinical practice guideline update on ovarian suppression. J Clin Oncol. 2016;34(14):1689-1701. doi:10.1200/JCO.2015.65.9573 [PubMed 26884586]
  17. Burstein HJ, Lacchetti C, Anderson H, et al. Adjuvant endocrine therapy for women with hormone receptor-positive breast cancer: ASCO clinical practice guideline focused update. J Clin Oncol. 2019;37(5):423-438. doi:10.1200/JCO.18.01160 [PubMed 30452337]
  18. Caballero ML, Krantz MS, Quirce S, Phillips EJ, Stone CA Jr. Hidden dangers: Recognizing excipients as potential causes of drug and vaccine hypersensitivity reactions. J Allergy Clin Immunol Pract. 2021;9(8):2968-2982. doi:10.1016/j.jaip.2021.03.002 [PubMed 33737254]
  19. Camcevi (leuprolide mesylate) [prescribing information]. Raleigh, NC: Accord BioPharma Inc; March 2024.
  20. Carel JC, Eugster EA, Rogol A, et al. Consensus statement on the use of gonadotropin-releasing hormone analogs in children. Pediatrics. 2009;123(4):752-762. doi:10.1542/peds.2008-1783 [PubMed 19332438]
  21. Carel JC, Lahlou N, Guazzarotti L, et al. Treatment of central precocious puberty with depot leuprorelin. French Leuprorelin Trial Group. Eur J Endocrinol. 1995;132(6):699-704. doi:10.1530/eje.0.1320699 [PubMed 7788009]
  22. Centers for Disease Control (CDC). Neonatal deaths associated with use of benzyl alcohol—United States. MMWR Morb Mortal Wkly Rep. 1982;31(22):290-291. http://www.cdc.gov/mmwr/preview/mmwrhtml/00001109.htm [PubMed 6810084]
  23. Centers for Disease Control (CDC). Unusual syndrome with fatalities among premature infants: association with a new intravenous vitamin E product. MMWR Morb Mortal Wkly Rep. 1984;33(14):198-199. http://www.cdc.gov/mmwr/preview/mmwrhtml/00000319.htm. [PubMed 6423951]
  24. Chavez B, Reilly T. Manic and psychotic symptoms following subcutaneous leuprolide in a male patient with no prior psychiatric history. J Clin Psychiatry. 2010;71(12):1696-1698. doi:10.4088/JCP.10l06190yel [PubMed 21190641]
  25. Cook T, Sheridan WP. Development of GnRH antagonists for prostate cancer: new approaches to treatment. Oncologist. 2000;5(2):162-168. doi:10.1634/theoncologist.5-2-162 [PubMed 10794807]
  26. Crawford ED, Eisenberger MA, McLeod DG, et al. A controlled trial of leuprolide with and without flutamide in prostatic carcinoma. N Engl J Med. 1989;321(7):419-424. doi:10.1056/NEJM198908173210702. Erratum in: N Engl J Med 1989;321(20):1420. [PubMed 2503724]
  27. Dangle P, Palit V, Sundaram SK, Weston P. Noninfective cutaneous granuloma with leuprorelin acetate--reality or myth. Urology. 2007;69(4):779.e5-e6. doi:10.1016/j.urology.2007.02.013 [PubMed 17445679]
  28. Dawood MY, Ramos J, Khan-Dawood FS. Depot leuprolide acetate versus danazol for treatment of pelvic endometriosis: changes in vertebral bone mass and serum estradiol and calcitonin. Fertil Steril. 1995;63(6):1177-1183. doi:10.1016/s0015-0282(16)57593-1 [PubMed 7750585]
  29. Di Lauro L, Pizzuti L, Barba M, et al. Role of gonadotropin-releasing hormone analogues in metastatic male breast cancer: results from a pooled analysis. J Hematol Oncol. 2015;8:53. doi:10.1186/s13045-015-0147-z [PubMed 25980944]
  30. Dittrich R, Binder H, Cupisti S, Hoffmann I, Beckmann MW, Mueller A. Endocrine treatment of male-to-female transsexuals using gonadotropin-releasing hormone agonist. Exp Clin Endocrinol Diabetes. 2005;113(10):586-592. doi:10.1055/s-2005-865900. [PubMed 16320157]
  31. Eligard (leuprolide acetate) injectable suspension [prescribing information]. Fort Collins, CO: Tolmar Inc; January 2024.
  32. Eligard (leuprolide acetate) [product monograph]. Oakville, Ontario, Canada: Innomar Strategies Inc; January 2024.
  33. Expert opinion. Senior Renal Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
  34. Fabiano AJ, George S. Pituitary Apoplexy After Initial Leuprolide Injection. World Neurosurg. 2016;95:616.e7-616.e9. doi:10.1016/j.wneu.2016.08.091 [PubMed 27586180]
  35. Fensolvi (leuprolide acetate) [prescribing information]. Fort Collins, CO: Tolmar; April 2023.
  36. Fensolvi (leuprolide acetate) [prescribing information]. Fort Collins, CO: Tolmar Pharmaceuticals Inc; April 2022.
  37. Francis PA, Pagani O, Fleming GF, et al; SOFT and TEXT Investigators and the International Breast Cancer Study Group. Tailoring adjuvant endocrine therapy for premenopausal breast cancer. N Engl J Med. 2018;379(2):122-137. doi:10.1056/NEJMoa1803164 [PubMed 29863451]
  38. Fujisaki A, Kondo Y, Goto K, Morita T. Life-threatening anaphylaxis to leuprorelin acetate depot: case report and review of the literature. Int J Urol. 2012;19(1):81-84. doi:10.1111/j.1442-2042.2011.02886.x [PubMed 22050405]
  39. Fuld K, Chi C, Neely EK. A randomized trial of 1- and 3-month depot leuprolide doses in the treatment of central precocious puberty. J Pediatr. 2011;159(6):982-7.e1. doi:10.1016/j.jpeds.2011.05.036 [PubMed 21798557]
  40. Gatti J, Brinker A, Avigan M. Spontaneous reports of seizure in association with leuprolide (lupron depot), goserelin (zoladex implant), and naferelin (synarel nasal spray). Obstet Gynecol. 2013;121(5):1107. doi:10.1097/AOG.0b013e31828c9cb3 [PubMed 23635751]
  41. Gava G, Cerpolini S, Martelli V, Battista G, Seracchioli R, Meriggiola MC. Cyproterone acetate vs leuprolide acetate in combination with transdermal oestradiol in transwomen: a comparison of safety and effectiveness. Clin Endocrinol (Oxf). 2016;85(2):239-46. doi:10.1111/cen.13050 [PubMed 26932202]
  42. Gnanaraj J, Saif MW. Hypersensitivity vasculitis associated with leuprolide (Lupron). Cutan Ocul Toxicol. 2010;29(3):224-227. doi:10.3109/15569527.2010.487505 [PubMed 20470239]
  43. Guay DR. Drug treatment of paraphilic and nonparaphilic sexual disorders. Clin Ther. 2009;31(1):1-31. doi:10.1016/j.clinthera.2009.01.009 [PubMed 19243704]
  44. Hassett MJ, Somerfield MR, Baker ER, et al. Management of male breast cancer: ASCO guideline. J Clin Oncol. 2020;38(16):1849-1863. doi:10.1200/JCO.19.03120 [PubMed 32058842]
  45. Heger S, Partsch CJ, Sippell WG. Long-term outcome after depot gonadotropin-releasing hormone agonist treatment of central precocious puberty: Final height, body proportions, body composition, bone mineral density, and reproductive function. J Clin Endocrinol Metab. 1999;84(12):4583-4590.
  46. Hembree WC, Cohen-Kettenis PT, Gooren L, et al. Endocrine treatment of gender-dysphoric/gender-incongruent persons: an Endocrine Society clinical practice guideline. Endocr Pract. 2017;23(12):1437. doi:10.4158/1934-2403-23.12.1437 [PubMed 29320642]
  47. Houk CP, Kunselman AR, Lee PA. The diagnostic value of a brief GnRH analogue stimulation test in girls with central precocious puberty: a single 30-minute post-stimulation LH sample is adequate. J Pediatr Endocrinol Metab. 2008;21(12):1113-1118. doi:10.1515/jpem.2008.21.12.1113 [PubMed 19189683]
  48. Hu JR, Duncan MS, Morgans AK, et al. Cardiovascular effects of androgen deprivation therapy in prostate cancer: Contemporary meta-analyses. Arterioscler Thromb Vasc Biol. 2020;40(3):e55-e64. doi:10.1161/ATVBAHA.119.313046 [PubMed 31969015]
  49. "Inactive" ingredients in pharmaceutical products: update (subject review). American Academy of Pediatrics Committee on Drugs. Pediatrics. 1997;99(2):268-278. doi:10.1542/peds.99.2.268 [PubMed 9024461]
  50. Isaksson M, Jansson L. Contact allergy to Tween 80 in an inhalation suspension. Contact Dermatitis. 2002;47(5):312-323. doi:10.1034/j.1600-0536.2002.4705104.x [PubMed 12534540]
  51. Jaggi S, Slone H, Strauss R, Zaeeter W, Pallie V. SUN-421 leuprolide injection induced pituitary apoplexy. J Endocrine Society. 2019;3(suppl 1);SUN-421. https://doi.org/10.1210/js.2019-SUN-421
  52. Kaplowitz P, Bloch C; Section on Endocrinology, American Academy of Pediatrics. Evaluation and referral of children with signs of early puberty. Pediatrics. 2016;137(1):10.1542/peds.2015-3732. doi:10.1542/peds.2015-3732 [PubMed 26668298]
  53. Kaya A, Cayir A, Turan MI, Ozkan B. An examination of the effects of leuprolide acetate used in the treatment of central precocious puberty on bone mineral density and 25-hydroxy vitamin D. West Indian Med J. 2015;64(2):104-107. doi:10.7727/wimj.2014.346 [PubMed 26360682]
  54. Keating NL, O'Malley AJ, Smith MR. Diabetes and cardiovascular disease during androgen deprivation therapy for prostate cancer. J Clin Oncol. 2006;24(27):4448-4456. doi:10.1200/JCO.2006.06.2497 [PubMed 16983113]
  55. Kirkgoz T, Karakoc-Aydiner E, Bugrul F, et al. Management of systemic hypersensitivity reactions to gonadotropin-releasing hormone analogues during treatment of central precocious puberty. Horm Res Paediatr. 2020;93(1):66-72. doi:10.1159/000505329 [PubMed 31972562]
  56. Klein KO, Mauras N, Nayak S, et al. Efficacy and safety of leuprolide acetate 6-month depot for the treatment of central precocious puberty: a phase 3 study. J Endocr Soc. 2023;7(7):bvad071. doi:10.1210/jendso/bvad071 [PubMed 37334213]
  57. Kluger N, Hahtola S, Lempinen T, Jeskanen L. Cutaneous granulomas caused by subcutaneous injections of leuprorelin acetate. Presse Med. 2017;46(10):966-968. doi:10.1016/j.lpm.2017.08.004 [PubMed 28919272]
  58. Krishna KB, Fuqua JS, Rogol AD, et al. Use of gonadotropin-releasing hormone analogs in children: update by an international consortium. Horm Res Paediatr. 2019;91(6):357-372. doi:10.1159/000501336 [PubMed 31319416]
  59. Krueger RB, Kaplan MS. Depot-leuprolide acetate for treatment of paraphilias: a report of twelve cases. Arch Sex Behav. 2001;30(4):409-422. doi:10.1023/a:1010213432606 [PubMed 11446201]
  60. Lam C, Tjon J, Hamilton J, Ahmet AH. Recurrent anaphylaxis associated with gonadotropin-releasing hormone analogs: case report and review of the literature. Pharmacotherapy. 2006;26(12):1811-1815. doi:10.1592/phco.26.12.1811 [PubMed 17125443]
  61. Lambertini M, Moore HCF, Leonard RCF, et al. Gonadotropin-releasing hormone agonists during chemotherapy for preservation of ovarian function and fertility in premenopausal patients with early breast cancer: a systematic review and meta-analysis of individual patient-level data. J Clin Oncol. 2018;36(19):1981-1990. doi:10.1200/JCO.2018.78.0858 [PubMed 29718793]
  62. Laufer MR. Current approaches to optimizing the treatment of endometriosis in adolescents. Gynecol Obstet Invest. 2008;66(Suppl 1):19-27. doi:10.1159/000148027 [PubMed 18936548]
  63. Lee PA, Klein K, Mauras N, Lev-Vaisler T, Bacher P. 36-month treatment experience of two doses of leuprolide acetate 3-month depot for children with central precocious puberty. J Clin Endocrinol Metab. 2014;99(9):3153-3159. doi: 10.1210/jc.2013-4471 [PubMed 24926950]
  64. Letterie GS, Stevenson D, Shah A. Recurrent anaphylaxis to a depot form of GnRH analogue. Obstet Gynecol. 1991;78(5 pt 2):943-946. [PubMed 1923237]
  65. Leuprolide acetate injection [prescribing information]. E. Windsor, NJ: AuroMedics Pharma LLC; March 2021.
  66. Leuprolide acetate 22.5 mg Mixject (3 Month) [prescribing information]. Warren NJ: Cipla USA Inc; November 2023.
  67. Levine GN, D'Amico AV, Berger P, et al; American Heart Association Council on Clinical Cardiology and Council on Epidemiology and Prevention, the American Cancer Society, and the American Urological Association. Androgen-deprivation therapy in prostate cancer and cardiovascular risk: a science advisory from the American Heart Association, American Cancer Society, and American Urological Association: endorsed by the American Society for Radiation Oncology. Circulation. 2010;121(6):833-840. doi:10.1161/CIRCULATIONAHA.109.192695 [PubMed 20124128]
  68. Lim CN, Salem AH. A semi-mechanistic integrated pharmacokinetic/pharmacodynamic model of the testosterone effects of the gonadotropin-releasing hormone agonist leuprolide in prostate cancer patients. Clin Pharmacokinet. 2015;54(9):963-973. doi:10.1007/s40262-015-0251-9 [PubMed 25791895]
  69. Loren AW, Mangu PB, Beck LN, et al; American Society of Clinical Oncology. Fertility preservation for patients with cancer: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol. 2013;31(19):2500-2510. doi:10.1200/JCO.2013.49.2678 [PubMed 23715580]
  70. Lucente P, Iorizzo M, Pazzaglia M. Contact sensitivity to Tween 80 in a child. Contact Dermatitis. 2000;43(3):172. [PubMed 10985636]
  71. Lüchinger AB, Mijatovic V, Rustemeyer T, Hompes PG. Anaphylactic reaction to different gonadotropin-releasing hormone agonists for the treatment of endometriosis. Am J Med Sci. 2011;341(3):240-242. doi:10.1097/MAJ.0b013e31820094da [PubMed 21233692]
  72. Lupron (leuprolide acetate) [prescribing information]. North Chicago, IL: AbbVie Inc; March 2019.
  73. Lupron (leuprolide acetate) [prescribing information]. North Chicago, IL: AbbVie Inc; May 2017.
  74. Lupron Depot (leuprolide acetate) [product monograph]. St Laurent, Quebec, Canada: AbbVie Corp; March 2024.
  75. Lupron Depot 1-month 7.5 mg, 3-month 22.5 mg, 4-month 30 mg, 6-month 45 mg (leuprolide acetate) [prescribing information]. North Chicago, IL: AbbVie Inc; March 2024.
  76. Lupron Depot 3.75 mg (leuprolide acetate) [prescribing information]. North Chicago, IL: AbbVie Inc; October 2023.
  77. Lupron Depot 3-month 11.25 mg (leuprolide acetate) [prescribing information]. North Chicago, IL: AbbVie Inc; March 2020.
  78. Lupron Depot-PED (leuprolide acetate) [prescribing information]. North Chicago, IL: AbbVie Inc; April 2022.
  79. Lupron Depot-PED (leuprolide acetate) [prescribing information]. North Chicago, IL: AbbVie Inc; April 2023.
  80. Lyon AR, López-Fernández T, Couch LS, et al; ESC Scientific Document Group. 2022 ESC guidelines on cardio-oncology developed in collaboration with the European Hematology Association (EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS). Eur Heart J. 2022;43(41):4229-4361. doi:10.1093/eurheartj/ehac244 [PubMed 36017568]
  81. Magon N. Gonadotropin releasing hormone agonists: Expanding vistas. Indian J Endocrinol Metab. 2011;15(4):261-267. doi:10.4103/2230-8210.85575 [PubMed 22028996]
  82. Margel D, Peer A, Ber Y, et al. Cardiovascular morbidity in a randomized trial comparing GnRH agonist and GnRH antagonist among patients with advanced prostate cancer and preexisting cardiovascular disease. J Urol. 2019;202(6):1199-1208. doi:10.1097/JU.0000000000000384 [PubMed 31188734]
  83. McNeil BD, Pundir P, Meeker S, et al. Identification of a mast-cell-specific receptor crucial for pseudo-allergic drug reactions. Nature. 2015;519(7542):237-241. doi:10.1038/nature14022 [PubMed 25517090]
  84. Melloni C, Roe MT. Androgen deprivation therapy and cardiovascular disease. Urol Oncol. 2020;38(2):45-52. doi:10.1016/j.urolonc.2019.02.010 [PubMed 30879969]
  85. Mericq V, Lammoglia JJ, Unanue N, et al. Comparison of three doses of leuprolide acetate in the treatment of central precocious puberty: preliminary results. Clin Endocrinol (Oxf). 2009;71(5):686-690. doi: 10.1111/j.1365-2265.2009.03584.x [PubMed 19302581]
  86. Metzger ML, Meacham LR, Patterson B, et al.. Female reproductive health after childhood, adolescent, and young adult cancers: guidelines for the assessment and management of female reproductive complications. J Clin Oncol. 2013;31(9):1239-1247. doi:10.1200/JCO.2012.43.5511 [PubMed 23382474]
  87. Mitchell BG, Adams AL, Thandi PK. Psychotic exacerbation following subcutaneous leuprolide in a male patient with previous history of schizophrenia. Prim Care Companion CNS Disord. 2017;19(2). doi:10.4088/PCC.16l02038 [PubMed 28387484]
  88. National Institute for Health and Care Excellence (NICE). Drug allergy: Diagnosis and management. Clinical guideline; 2014. https://www.nice.org.uk/guidance/cg183/resources/drug-allergy-diagnosis-and-management-pdf-35109811022821
  89. Ökdemir D, Hatipoğlu N, Akar HH, et al. A patient developing anaphylaxis and sensitivity to two different GnRH analogues and a review of literature. J Pediatr Endocrinol Metab. 2015;28(7-8):923-925. doi:10.1515/jpem-2014-0402 [PubMed 25719301]
  90. Okwuosa TM, Morgans A, Rhee JW, et al; American Heart Association Cardio-Oncology Subcommittee of the Council on Clinical Cardiology and the Council on Genomic and Precision Medicine; Council on Arteriosclerosis, Thrombosis and Vascular Biology; and Council on Cardiovascular Radiology and Intervention. Impact of hormonal therapies for treatment of hormone-dependent cancers (breast and prostate) on the cardiovascular system: Effects and modifications: A scientific statement from the American Heart Association. Circ Genom Precis Med. 2021;14(3):e000082. doi:10.1161/HCG.0000000000000082 [PubMed 33896190]
  91. Oktay K, Harvey BE, Partridge AH, et al. Fertility preservation in patients with cancer: ASCO clinical practice guideline update. J Clin Oncol. 2018;36(19):1994-2001. doi:10.1200/JCO.2018.78.1914 [PubMed 29620997]
  92. Omar AA, Nyaga G, Mungai LNW. Pseudotumor cerebri in patient on leuprolide acetate for central precocious puberty. Int J Pediatr Endocrinol. 2020;2020(1):22. doi:10.1186/s13633-020-00092-4 [PubMed 33292495]
  93. Oshima M, Murao K, Ishigami T, Kubo Y. Drug eruption induced by gonadotropin-releasing hormone analogs accompanying radiation-recall phenomenon. J Dermatol. 2012;39(12):1080-1081. doi:10.1111/j.1346-8138.2012.01576.x [PubMed 22568476]
  94. Palomba S, Affinito P, Tommaselli GA, Nappi C. A clinical trial of the effects of tibolone administered with gonadotropin-releasing hormone analogues for the treatment of uterine leiomyomata. Fertil Steril. 1998;70(1):111-118. doi:10.1016/s0015-0282(98)00128-9 [PubMed 9660431]
  95. Pong YH, Lu YC, Tsai VF, Huang PL, Hsieh JT, Chang HC. Acute manic and psychotic symptoms following subcutaneous leuprolide acetate in a male patient without prior psychiatric history: A case report and literature review. 2014;25(1):22-24. https://doi.org/10.1016/j.urols.2013.05.010
  96. Practice Committee of the American Society for Reproductive Medicine (ASRM). Endometriosis and infertility: a committee opinion. Fertil Steril. 2012;98(3):591-598. doi:10.1016/j.fertnstert.2012.05.031 [PubMed 22704630]
  97. Refer to manufacturer's labeling.
  98. Reilly DR, Delva NJ, Hudson RW. Protocols for the use of cyproterone, medroxyprogesterone, and leuprolide in the treatment of paraphilia. Can J Psychiatry. 2000;45(6):559-563. doi:10.1177/070674370004500608 [PubMed 10986575]
  99. Roden DM. Drug-induced prolongation of the QT interval. N Engl J Med. 2004;350(10):1013-1022. doi:10.1056/NEJMra032426 [PubMed 14999113]
  100. Rugo HS, Rumble RB, Macrae E, et al. Endocrine therapy for hormone receptor-positive metastatic breast cancer: American Society of Clinical Oncology Guideline. J Clin Oncol. 2016;34(25):3069-3103. doi:10.1200/JCO.2016.67.1487 [PubMed 27217461]
  101. Saad E, Babkir A, Awadelkarim AM, Qureshi F. Leuprolide-induced hyperosmolar hyperglycemic state in an elderly patient: a case report and literature review. Cureus. 2022;14(7):e26993. doi:10.7759/cureus.26993 [PubMed 35865181]
  102. Sadler Gallagher J, Feldman HA, Stokes NA, et al. The effects of gonadotropin-releasing hormone agonist combined with add-back therapy on quality of life for adolescents with endometriosis: A randomized controlled trial. J Pediatr Adolesc Gynecol. 2017;30(2):215-222. doi:10.1016/j.jpag.2016.02.008 [PubMed 26927501]
  103. Saruki K, Sekihara T, Mashimo M, Matsuo H, Sekiguchi H. Leuprorelin acetate blood levels and dialysance after the administration of sustained-release leuprorelin acetate in a dialysis case complicated by prostate cancer. Prostate. 1998;34(3):191-194. doi:10.1002/(sici)1097-0045(19980215)34:3<191::aid-pros6>3.0.co;2-l [PubMed 9492847]
  104. Sasagawa Y, Tachibana O, Nakagawa A, Koya D, Iizuka H. Pituitary apoplexy following gonadotropin-releasing hormone agonist administration with gonadotropin-secreting pituitary adenoma. J Clin Neurosci. 2015;22(3):601-603. doi:10.1016/j.jocn.2014.08.015 [PubMed 25455737]
  105. Sathasivam A, Garibaldi L, Shapiro S, Godbold J, Rapaport R. Leuprolide stimulation testing for the evaluation of early female sexual maturation. Clin Endocrinol (Oxf). 2010;73(3):375-381. doi:10.1111/j.1365-2265.2010.03796.x [PubMed 20184599]
  106. Sathasivam A, Rosenberg HK, Shapiro S, Wang H, Rapaport R. Pelvic ultrasonography in the evaluation of central precocious puberty: comparison with leuprolide stimulation test. J Pediatr. 2011;159(3):490-495. doi:10.1016/j.jpeds.2011.02.032 [PubMed 21489559]
  107. Shahinian VB, Kuo YF, Freeman JL, Goodwin JS. Risk of fracture after androgen deprivation for prostate cancer. N Engl J Med. 2005;352(2):154-164. doi:10.1056/NEJMoa041943 [PubMed 15647578]
  108. Shalin SC, Brantley J, Diwan AH. Follicular mucinosis and mycosis-fungoides-like drug eruption due to leuprolide acetate: a case report and review. J Cutan Pathol. 2012;39(11):1022-1025. doi:10.1111/j.1600-0560.2012.01980.x [PubMed 22882386]
  109. Shelley WB, Talanin N, Shelley ED. Polysorbate 80 hypersensitivity. Lancet. 1995;345(8960):1312-1313. doi:10.1016/s0140-6736(95)90963-x [PubMed 7746084]
  110. Shiota M, Tokuda N, Kanou T, Yamasaki H. Injection-site granulomas resulting from the administration of both leuprorelin acetate and goserelin acetate for the treatment of prostatic cancer. J Nippon Med Sch. 2007;74(4):306-308. doi:10.1272/jnms.74.306 [PubMed 17878701]
  111. Smith MR. Treatment-related osteoporosis in men with prostate cancer. Clin Cancer Res. 2006;12(20 Pt 2):6315s-6319s. doi:10.1158/1078-0432.CCR-06-0846 [PubMed 17062721]
  112. Smith MR, Klotz L, Persson BE, Olesen TK, Wilde AA. Cardiovascular safety of degarelix: results from a 12-month, comparative, randomized, open label, parallel group phase III trial in patients with prostate cancer. J Urol. 2010;184(6):2313-2319. doi:10.1016/j.juro.2010.08.012 [PubMed 20952020]
  113. Smith MR, Lee H, Nathan DM. Insulin sensitivity during combined androgen blockade for prostate cancer. J Clin Endocrinol Metab. 2006;91(4):1305-1308. doi:10.1210/jc.2005-2507 [PubMed 16434464]
  114. Spry NA, Galvão DA, Davies R, et al. Long-term effects of intermittent androgen suppression on testosterone recovery and bone mineral density: results of a 33-month observational study. BJU Int. 2009;104(6):806-812. doi:10.1111/j.1464-410X.2009.08458.x [PubMed 19281463]
  115. Tanaka T, Niimi H, Matsuo N, et al. Results of long-term follow-up after treatment of central precocious puberty with leuprorelin acetate: evaluation of effectiveness of treatment and recovery of gonadal function. The TAP-144-SR Japanese Study Group on Central Precocious Puberty. J Clin Endocrinol Metab. 2005;90(3):1371-1376. doi:10.1210/jc.2004-1863 [PubMed 15598675]
  116. Tang J, Weiter JJ. Branch retinal artery occlusion after injection of a long-acting risperidone preparation. Ann Intern Med. 2007;147(4):283-284. doi:10.7326/0003-4819-147-4-200708210-00021 [PubMed 17709768]
  117. Tan MG, Worley B, Kim WB, Ten Hove M, Beecker J. Drug-induced intracranial hypertension: A systematic review and critical assessment of drug-induced causes. Am J Clin Dermatol. 2020;21(2):163-172. doi:10.1007/s40257-019-00485-z [PubMed 31741184]
  118. Tanios G, Mungo NA, Kapila A, Bajaj K. Pituitary apoplexy: a rare complication of leuprolide therapy in prostate cancer treatment. BMJ Case Rep. 2017;2017:bcr2016218514. doi:10.1136/bcr-2016-218514 [PubMed 28710301]
  119. Tevaarwerk AJ, Wang M, Zhao F, et al. Phase III comparison of tamoxifen versus tamoxifen plus ovarian function suppression in premenopausal women with node-negative, hormone receptor-positive breast cancer (E-3193, INT-0142): a trial of the Eastern Cooperative Oncology Group. J Clin Oncol. 2014;32(35):3948-3958. doi:10.1200/JCO.2014.55.6993 [PubMed 25349302]
  120. Thibaut F, Cosyns P, Fedoroff JP, et al; WFSBP Task Force on Paraphilias. The World Federation of Societies of Biological Psychiatry (WFSBP) 2020 guidelines for the pharmacological treatment of paraphilic disorders. World J Biol Psychiatry. 2020;21(6):412-490. doi:10.1080/15622975.2020.1744723 [PubMed 32452729]
  121. Thompson IM. Flare associated with LHRH-agonist therapy. Rev Urol. 2001;3 suppl 3(suppl 3):S10-S104. [PubMed 16986003]
  122. Thompson IM, Zeidman EJ, Rodriguez FR. Sudden death due to disease flare with luteinizing hormone-releasing hormone agonist therapy for carcinoma of the prostate. J Urol. 1990;144(6):1479-1480. doi:10.1016/s0022-5347(17)39774-4 [PubMed 2122011]
  123. Tisdale JE, Chung MK, Campbell KB, et al; American Heart Association Clinical Pharmacology Committee of the Council on Clinical Cardiology and Council on Cardiovascular and Stroke Nursing. Drug-induced arrhythmias: A scientific statement from the American Heart Association. Circulation. 2020;142(15):e214-e233. doi:10.1161/CIR.0000000000000905 [PubMed 32929996]
  124. Tisdale JE, Jaynes HA, Kingery JR, et al. Development and validation of a risk score to predict QT interval prolongation in hospitalized patients. Circ Cardiovasc Qual Outcomes. 2013;6(4):479-487. doi:10.1161/CIRCOUTCOMES.113.000152. Erratum in: Circ Cardiovasc Qual Outcomes. 2013;6(6):e57. [PubMed 23716032]
  125. Tung YC, Lee JS, Tsai WY, Hsiao PH. The effects of gonadotropin releasing hormone analogue therapy on girls with gonadotropin-dependent precocious puberty. J Formos Med Assoc. 2007;106(10):826-831. doi:10.1016/S0929-6646(08)60047-9 [PubMed 17964961]
  126. US Department of Health and Human Services; Centers for Disease Control and Prevention; National Institute for Occupational Safety and Health. NIOSH list of antineoplastic and other hazardous drugs in healthcare settings 2016. Updated September 2016. Accessed October 5, 2016. https://www.cdc.gov/niosh/docs/2016-161/default.html.
  127. US Food and Drug Administration (FDA). Supplement approval. https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2017/019010Orig1s039ltr.pdf. Published July 11, 2017. Accessed August 2, 2023.
  128. Villalba-Cuesta PL, Álvaro-Vegue C, Carrasco-Muñoz CG, Gomis-Goti C, García-Villa A. Interstitial pneumonitis associated with leuprorelin acetate for a prostate cancer: a case report. J Oncol Pharm Pract. 2022;28(8):1910-1913. doi:10.1177/10781552221084058 [PubMed 35234109]
  129. Vurallı D, Alikaşifoğlu A, İyigün İ, et al. Treatment with depot leuprolide acetate in girls with idiopathic precocious puberty: what parameter should be used in deciding on the initial dose?. J Clin Res Pediatr Endocrinol. 2020;12(1):37-44. doi:10.4274/jcrpe.galenos.2019.2019.0060 [PubMed 31347350]
  130. Warner E, Glass K, Foong S, Sandwith E. Update on fertility preservation for younger women with breast cancer. CMAJ. 2020;192(35):E1003-E1009. doi:10.1503/cmaj.200245 [PubMed 32868272]
  131. Warrington R, Silviu-Dan F, Wong T. Drug allergy. Allergy Asthma Clin Immunol. 2018;14(Suppl 2):60. doi:10.1186/s13223-018-0289-y [PubMed 30275849]
  132. Waxman J, Man A, Hendry WF, et al. Importance of early tumour exacerbation in patients treated with long acting analogues of gonadotrophin releasing hormone for advanced prostatic cancer. Br Med J (Clin Res Ed). 1985;291(6506):1387-1388. doi:10.1136/bmj.291.6506.1387 [PubMed 2933122]
  133. Yasukawa K, Sawamura D, Sugawara H, Kato N. Leuprorelin acetate granulomas: case reports and review of the literature. Br J Dermatol. 2005;152(5):1045-1047. doi:10.1111/j.1365-2133.2005.06341.x [PubMed 15888168]
  134. Zeulide Depot (leuprolide acetate) [product monograph]. Mississauga, Ontario, Canada: Verity Pharmaceuticals Inc; January 2024.
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