Subcutaneous (SC), Intramuscular (IM)
- Injection (SC): 1 mg/0.2 mL (daily formulation)
- Depot Injection (IM): 3.75 mg (1-month), 7.5 mg (1-month), 11.25 mg (3-month), 22.5 mg (3-month), 30 mg (4-month)
INDICATIONS + DOSING — FOR CLINICIAN USE ONLY
Primary Indications (Approved / Standard in India)
- Advanced Hormone-Sensitive Prostate Cancer
Parameter Recommendation
Starting dose 3.75 mg IM depot once monthly OR 7.5 mg IM depot once monthly
Titration Not applicable
Usual maintenance dose 3.75 mg monthly OR 11.25 mg every 3 months OR 22.5 mg every 3 months
Maximum dose As per approved depot formulation selected
Key Clinical Notes:
- Initiate anti-androgen therapy (e.g., bicalutamide 50 mg daily) at least 3 days before first leuprolide injection and continue for 2–4 weeks to prevent tumour flare
- Monitor serum testosterone — target castrate levels (<50 ng/dL)
- Continue until disease progression or intolerable toxicity
- Endometriosis
Parameter Recommendation
Starting dose 3.75 mg IM once monthly
Titration Not applicable
Usual maintenance dose 3.75 mg monthly OR 11.25 mg every 3 months
Maximum dose 11.25 mg every 3 months
Key Clinical Notes:
- Maximum treatment duration: 6 months (due to bone loss risk)
- Add-back therapy recommended: low-dose norethindrone (5 mg daily) or combined estrogen-progestin to reduce hypoestrogenic symptoms and bone loss
- May repeat course after reassessment if symptoms recur
- Uterine Leiomyomas (Fibroids) — Preoperative Size Reduction
Parameter Recommendation
Starting dose 3.75 mg IM once monthly
Titration Not applicable
Usual maintenance dose 3.75 mg monthly
Maximum dose 3.75 mg monthly for up to 6 months
Key Clinical Notes:
- Duration: 3–6 months preoperatively
- Reduces uterine and fibroid volume by 30–50%
- Corrects preoperative anaemia
- Consider add-back therapy if used beyond 3 months
- Hormone Receptor-Positive Breast Cancer (Premenopausal Women — Ovarian Suppression)
Parameter Recommendation
Starting dose 3.75 mg IM once monthly
Titration Not applicable
Usual maintenance dose 3.75 mg monthly OR 11.25 mg every 3 months
Maximum dose As per oncology protocol
Key Clinical Notes:
- Used in combination with tamoxifen or aromatase inhibitor
- Duration: 2–5 years as part of adjuvant endocrine therapy
- Specialist only (Medical Oncology)
- Confirm ovarian suppression with serum estradiol levels
- Central Precocious Puberty (CPP)
See Paediatric Dosing Section
Secondary Indications – Adults Only (Off-label)
- Assisted Reproductive Technology (ART) — Pituitary Downregulation — OFF-LABEL
- Starting dose: 0.5–1 mg SC daily
- Titration: Not applicable
- Usual maintenance dose: 0.5–1 mg SC daily
- Maximum dose: 1 mg SC daily
- Duration: Begin in mid-luteal phase of preceding cycle; continue until adequate downregulation confirmed (typically 10–14 days)
- Specialist only (Reproductive Medicine/IVF centres)
- Evidence: Indian Fertility Society protocols; established IVF practice
- Gender-Affirming Hormone Therapy (Male-to-Female) — OFF-LABEL
- Starting dose: 3.75 mg IM monthly
- Titration: Not applicable
- Usual maintenance dose: 3.75 mg monthly OR 11.25 mg every 3 months
- Maximum dose: As per specialist protocol
- Duration: Long-term; individualized
- Specialist only (Endocrinology with expertise in gender medicine)
- Evidence: International guidelines; limited formal Indian guidance — use under specialist supervision only
PAEDIATRIC DOSING (Specialist Only)
Primary Indications (Approved / Standard in India)
Central Precocious Puberty (CPP)
- Specialist only (Paediatric Endocrinology)
Weight-Based Dosing (Monthly IM Depot):
Body Weight Dose (IM Monthly)
<25 kg 7.5 mg once monthly
25–37.5 kg 11.25 mg once monthly
37.5 kg 15 mg once monthly
Alternative 3-Month Depot:
- 11.25 mg IM every 3 months (for appropriate weight categories)
Parameter Recommendation
Starting dose As per weight-based table above
Titration Adjust based on clinical and biochemical response
Usual maintenance dose Same as starting dose
Maximum dose 15 mg monthly
Key Clinical Notes:
- Confirm diagnosis with GnRH stimulation test before initiating therapy
- Goal: Suppression of pubertal progression and deceleration of bone age advancement
- Discontinue when chronological age appropriate for puberty (typically 11 years for girls, 12 years for boys)
Secondary Indications – Paediatric Doses (Off-label)
Not established in Indian guidelines. Off-label use outside CPP is NOT recommended without Paediatric Endocrinologist supervision.
Safety Monitoring (Paediatric Use):
- Serum LH, FSH, and sex steroids (estradiol or testosterone) at baseline, 1–2 months, then every 6 months
- Bone age assessment (X-ray left wrist) at baseline and every 6–12 months
- Growth velocity monitoring
- Pubertal staging (Tanner) at each visit
- Height prediction assessment annually
NOT recommended below 2 years of age.
- No dosage adjustment required in mild, moderate, or severe renal impairment
- Depot formulation is not significantly dialyzable
- Haemodialysis/peritoneal dialysis: No supplemental dosing required
- Mild impairment: No dosage adjustment required
- Moderate impairment: Use with caution; no specific dose reduction established but monitor for adverse effects
- Severe impairment: Limited data available; use with caution under specialist supervision
- Known hypersensitivity to leuprolide, other GnRH agonists, or any excipients
- Pregnancy (confirmed or suspected)
- Undiagnosed abnormal vaginal bleeding
- Hormone-independent (castration-resistant) prostate cancer
- Women with hormone receptor-negative breast cancer (no benefit expected)
- Tumour flare phenomenon: Initial rise in testosterone/estrogen may worsen symptoms in first 1–2 weeks (bone pain, urinary obstruction in prostate cancer; bleeding in fibroids) — always provide anti-androgen cover in prostate cancer
- Osteoporosis or risk factors for bone loss — baseline BMD assessment recommended for therapy >6 months
- Pre-existing cardiovascular disease — monitor for metabolic effects
- Diabetes mellitus — may affect glycaemic control
- Depression or psychiatric history — monitor for mood changes
- Seizure disorders — rare reports of convulsions
- Prolonged QT interval — use with caution with QT-prolonging medications
- Vertebral metastases with risk of spinal cord compression (prostate cancer) — close monitoring during initiation
Parameter Recommendation
Risk category Contraindicated (Category X equivalent)
Teratogenic risk Known teratogenicity in animal studies; fetal harm expected
Preferred alternatives Not applicable — drug must be avoided
When may be used Never during confirmed or suspected pregnancy
Monitoring Confirm negative pregnancy test before initiating therapy; ensure reliable contraception during treatment and for at least 1–2 months after discontinuation
Parameter Recommendation
Compatibility Not compatible with breastfeeding
Expected drug levels in milk Unknown; potential for hormonal effects on infant
Preferred alternatives Discontinue breastfeeding if leuprolide therapy essential
Infant monitoring Not applicable — avoid use during lactation
- Starting dose: Same as adult dosing (3.75 mg depot monthly or equivalent)
- Titration: Not applicable
- Depot formulations preferred for improved adherence
- Increased susceptibility to bone loss — baseline and periodic BMD assessment
- Cardiovascular risk — monitor lipid profile, blood glucose, blood pressure
- Falls risk due to potential musculoskeletal effects
- In prostate cancer: Regular PSA and testosterone monitoring essential
Interacting Drug Effect Mechanism Management
QT-prolonging drugs (amiodarone, sotalol, haloperidol, ondansetron, fluoroquinolones) Additive QT prolongation risk Pharmacodynamic interaction Avoid combination if possible; if essential, obtain baseline ECG and monitor QT interval
Interacting Drug Effect Management
Antidiabetic agents (metformin, sulfonylureas, insulin) Altered glucose tolerance due to hormonal changes Monitor blood glucose more frequently; adjust antidiabetic doses as needed
SSRIs/SNRIs May exacerbate mood disturbances and hot flushes Monitor for worsening depression or mood changes
Corticosteroids Additive risk of bone loss with prolonged use Consider BMD monitoring; ensure calcium and vitamin D supplementation
Tamoxifen Used together therapeutically in breast cancer Monitor for additive hot flushes and bone health; no dose adjustment needed
- Injection site reactions (pain, erythema, induration)
- Erectile dysfunction (males)
- Vaginal dryness and dyspareunia (females)
- Mood changes (irritability, emotional lability)
- Tumour flare: Worsening of symptoms (bone pain, urinary obstruction, spinal cord compression) in first 1–2 weeks — requires anti-androgen cover in prostate cancer; may require hospitalisation if severe
- Pituitary apoplexy: Rare; presents with sudden headache, visual changes, altered mental status — requires immediate neurosurgical evaluation
- Osteoporotic fractures: With prolonged therapy (>6 months)
- Cardiovascular events: Myocardial infarction, stroke — rare; monitor in high-risk patients
- QT prolongation: Rare; obtain baseline ECG in patients with cardiac history
- Severe depression/suicidal ideation: Rare; screen for psychiatric history before initiation
- Anaphylactic/hypersensitivity reactions: Rare
- Interstitial lung disease: Very rare
Baseline:
- Serum testosterone (males) or estradiol (females)
- LH, FSH (especially in CPP)
- Bone mineral density (DEXA) if therapy anticipated >6 months
- Blood glucose/HbA1c (diabetic patients)
- ECG (if cardiac history or QT-prolonging drug use)
- Pregnancy test (females of reproductive age)
After Initiation:
- Monitor for tumour flare symptoms during first 2–4 weeks (prostate cancer)
- Serum testosterone/estradiol at 1 month to confirm suppression
- PSA at 3–6 months (prostate cancer)
- Clinical assessment for injection site reactions
Long-term (>6 months):
- Blood glucose/HbA1c annually
- PSA every 3–6 months (prostate cancer)
- MRI pituitary if pituitary adenoma history
- In CPP: Bone age, growth velocity, and pubertal staging every 6–12 months
- Lupride Depot (Sun Pharma)
- Eligard (Astellas/Tolmar)
- Leuprogen (Bharat Serums)
- Luperel (Reliance Life Sciences)
- 1 mg SC injection (daily): ₹1,200–₹1,500 per vial
- 3.75 mg IM depot (1-month): ₹2,500–₹3,500
- 7.5 mg IM depot (1-month): ₹4,000–₹5,500
- 11.25 mg IM depot (3-month): ₹6,500–₹9,000
- 22.5 mg IM depot (3-month): ₹12,000–₹15,000
- Included in NLEM for CPP and oncology indications
- Available under government oncology programs for prostate and breast cancer
- Always initiate anti-androgen therapy (bicalutamide or flutamide) before first leuprolide dose in prostate cancer to prevent tumour flare — continue for at least 2–4 weeks
- In endometriosis and fibroids, add-back therapy with low-dose norethindrone or estrogen-progestin minimizes bone loss and hypoestrogenic symptoms without reducing efficacy — initiate from the start of treatment
- Depot formulations are not interchangeable — ensure correct formulation selected for intended dosing interval (1-month vs 3-month)
- Symptoms during first 2 weeks may mimic disease progression due to initial hormone surge — counsel patients appropriately to prevent unnecessary alarm or treatment changes
- For any therapy duration exceeding 6 months, baseline and annual BMD assessment is essential — consider bisphosphonates if significant bone loss occurs
- In CPP, discontinue treatment when chronological age is appropriate for puberty to allow normal pubertal progression
leuprolide; GnRH agonist; prostate cancer; endometriosis; uterine fibroids; central precocious puberty; hormonal therapy; depot injection; tumour flare; NLEM India
RxIndia v1.0 — 06 Apr 2025
- CDSCO approved prescribing information
- National List of Essential Medicines (NLEM) India 2022
- AIIMS Paediatric Endocrinology Protocols
- Indian Fertility Society Guidelines (ART protocols)
- Tata Memorial Centre Oncology Protocols
- Goodman & Gilman's The Pharmacological Basis of Therapeutics
- WHO Essential Medicines List (supportive — CPP indication)