INDICATIONS + DOSING — FOR CLINICIAN USE ONLY
Primary Indications (Approved / Standard in India)
- Hormone Receptor-Positive Breast Cancer (Postmenopausal Women)
Clinical Setting Starting Dose Titration Usual Maintenance Dose Maximum Dose Key Clinical Notes
Adjuvant treatment (early-stage) 2.5 mg once daily Not applicable 2.5 mg once daily 2.5 mg/day Continue for 5 years post-surgery; may follow 2–3 years of tamoxifen
Extended adjuvant (after 5 years tamoxifen) 2.5 mg once daily Not applicable 2.5 mg once daily 2.5 mg/day Duration typically up to 5 years based on clinical assessment
Advanced/metastatic disease 2.5 mg once daily Not applicable 2.5 mg once daily 2.5 mg/day Continue until disease progression or intolerable toxicity
Secondary Indications – Adults Only (Off-label)
- Ovulation Induction in Polycystic Ovary Syndrome (PCOS) — OFF-LABEL
- Starting dose: 2.5 mg once daily from Day 3–7 of menstrual cycle for 5 consecutive days
- Titration: May increase to 5 mg/day or 7.5 mg/day in subsequent cycles if ovulation not achieved
- Usual maintenance dose: 2.5–5 mg/day for 5 days per cycle
- Maximum dose: 7.5 mg/day for 5 days
- Duration: Up to 6 ovulatory cycles
- Monitoring: Serial follicular tracking with ultrasonography
- Evidence: Multiple RCTs support efficacy comparable or superior to clomiphene; widely used in Indian fertility practice
- Endometriosis-Associated Infertility — OFF-LABEL
- Dose: 2.5–5 mg once daily for 5 days as part of controlled ovarian stimulation
- Duration: Cycle-specific; used with or without GnRH analogues
- Evidence: Based on Indian gynaecology-oncology practice and limited clinical trials
PAEDIATRIC DOSING (Specialist Only)
Primary Indications (Approved / Standard in India):
Not applicable — no approved paediatric indications exist for letrozole.
Secondary Indications – Paediatric Doses (Off-label):
- Idiopathic Short Stature / Constitutionally Delayed Puberty in Males — OFF-LABEL
- Age: ≥10 years (NOT recommended below 10 years)
- Starting dose: 2.5 mg once daily
- Titration: Not applicable
- Usual maintenance dose: 2.5 mg once daily
- Duration: 1–2 years under specialist supervision
- Specialist only (Paediatric endocrinology)
- Evidence: Limited RCT data; used in select Indian paediatric endocrinology centres
- Precocious Puberty (Peripheral) — OFF-LABEL
- Age: ≥5 years (NOT recommended below 5 years)
- Starting dose: 0.5 mg once daily
- Titration: May increase to 2.5 mg once daily based on response
- Usual maintenance dose: 1–2.5 mg once daily
- Duration: As determined by specialist based on bone age progression
- Specialist only (Paediatric endocrinology)
- Evidence: Case series and limited observational data only
Safety Monitoring (All Paediatric Off-label Use):
- Bone age assessment (every 6–12 months)
- Growth velocity monitoring
- Bone mineral density (baseline and annually)
- Serum oestradiol/testosterone levels
- Liver function tests periodically
- Mild impairment (Child-Pugh A): No initial dose adjustment; monitor liver enzymes closely
- Moderate impairment (Child-Pugh B): Use with caution; no formal dose reduction established but closer monitoring advised
- Severe impairment (Child-Pugh C): Avoid use — reduced clearance and potential drug accumulation; if essential, specialist supervision mandatory
Known hypersensitivity to letrozole or any excipients
- Pregnancy (confirmed or suspected)
- Premenopausal endocrine status (for breast cancer indication — unless combined with ovarian suppression)
- Concurrent use of oestrogen-containing therapies (including HRT)
Osteoporosis or significant risk factors for bone loss (prior fragility fracture, steroid use, low BMI)
- Pre-existing hypercholesterolaemia or dyslipidaemia
- Cardiovascular disease or significant risk factors
- Moderate-to-severe hepatic impairment
- Severe renal impairment (CrCl <30 mL/min)
- Use in men or children — only under specialist supervision for specific off-label indications
Parameter Recommendation
Risk category Contraindicated (Category X equivalent)
Use in pregnancy Absolutely contraindicated; teratogenic potential with skeletal malformations reported in animal studies
Fertility treatment context Discontinue before expected ovulation; confirm negative pregnancy test before each cycle
Preferred alternatives Not applicable — avoid completely during confirmed pregnancy
Monitoring Pregnancy test mandatory before initiating fertility treatment cycles
Parameter Recommendation
Compatibility Not recommended during breastfeeding
Excretion in milk Unknown, but anticipated based on drug properties
Expected levels Data not available
Preferred alternatives Tamoxifen may be considered postpartum for hormone therapy if needed (consult specialist)
Infant monitoring If inadvertent exposure occurs: monitor feeding behaviour, growth, and development
Starting dose: 2.5 mg once daily (no age-based reduction required)
- Titration: Not applicable
- Higher baseline risk of osteoporosis and fractures — ensure bone health assessment
- Monitor cardiovascular status (lipid profile, blood pressure)
- Increased incidence of arthralgia — counsel regarding joint symptoms
- Assess fall risk given potential for dizziness
Interacting Drug Effect Management
Tamoxifen Reduces plasma letrozole concentration by ~38%; functional antagonism Do not co-administer for same indication
Oestrogens (HRT, combined oral contraceptives, vaginal oestrogen) Pharmacologically counteracts letrozole action Contraindicated during letrozole therapy
Interacting Drug Effect Management
Warfarin Potential enhancement of anticoagulant effect Monitor INR more frequently; adjust warfarin dose as needed
Statins Letrozole may independently elevate LDL cholesterol Monitor lipid profile; optimize statin therapy if required
CYP3A4 inducers (rifampicin, phenytoin, carbamazepine) May reduce letrozole plasma concentrations Clinical significance unclear; monitor for efficacy
•Hot flushes (30–50%)
- Arthralgia/myalgia (20–25%)
- Osteoporotic fractures (vertebral, hip, wrist) — especially with prolonged adjuvant use
- Thromboembolic events (DVT, pulmonary embolism) — rare
- Myocardial ischaemia/angina — rare, in predisposed individuals
- Hepatotoxicity (elevated transaminases, cholestasis) — rare
- Severe hypersensitivity reactions (angioedema, anaphylaxis) — very rare
Baseline:
- Lipid profile (total cholesterol, LDL, HDL, triglycerides)
- Bone mineral density (DEXA scan)
- Pregnancy test (mandatory before fertility treatment)
- Menopausal status confirmation (for breast cancer indication)
During Therapy:
- BMD assessment: Annually, especially if therapy duration >2 years or high fracture risk
- Lipid profile: Every 6–12 months
- Liver enzymes: Annually or if hepatic symptoms develop
- Clinical assessment: Joint symptoms, cardiovascular status at each visit
- ₹7–₹25 per 2.5 mg tablet (generic to branded)
- Not under NPPA price control
- Confirm postmenopausal status before initiating therapy for breast cancer (serum FSH/oestradiol if uncertain)
- For fertility induction, letrozole is often preferred over clomiphene citrate due to higher singleton pregnancy rates and more favourable endometrial response
- Proactively address bone health: recommend calcium (1000–1200 mg/day) and vitamin D (800–1000 IU/day) supplementation; consider bisphosphonates if T-score ≤ −2.0
- Avoid all oestrogen-containing preparations (including vaginal oestrogen for atrophic vaginitis) during breast cancer treatment — use non-hormonal alternatives
- Arthralgia is a common reason for treatment discontinuation — counsel patients, offer supportive measures (NSAIDs, physiotherapy), and encourage adherence
- In metastatic breast cancer, continue until disease progression; no evidence supports intermittent or time-limited dosing
letrozole; aromatase inhibitor; breast cancer; postmenopausal; ovulation induction; PCOS; fertility; bone loss; hormone receptor-positive; NLEM-excluded
RxIndia v1.0 — 02 May 2025
- CDSCO approved prescribing information
- AIIMS Treatment Protocols
- ICMR National Cancer Treatment Guidelines
- Indian Fertility Society Guidelines
- Goodman & Gilman's The Pharmacological Basis of Therapeutics
- RCT evidence (Letrozole vs Clomiphene for ovulation induction — off-label use documentation)