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Letrozole

Aromatase inhibitor (non-steroidal, third-generation) / anti-estrogen · Antineoplastic

Also known as Femara

START
2.5 mg OD (fixed dose); confirm postmenopausal status (FSH >40 IU/L); check baseline bone density (DEXA), lipid panel, liver function; ensure adequate calcium (1000-1200 mg) and vitamin D (800-1000 IU)
TYPICAL MAX
2.5 mg/day (no dose escalation)
STOP IF
Disease progression (advanced), completion of 5-year adjuvant course (may extend to 10 years in high risk), severe osteoporosis, intolerable side effects
WATCH
Bone density (DEXA at baseline, 1-2 years, then every 2 years), lipid panel annually, liver function if symptoms, fracture risk assessment, musculoskeletal symptoms
CDSCO approvedSchedule HJan AushadhiATC L02BG04
Renal dose adjustmenteGFR mL/min/1.73m²
FULLNo renal adjustment needed0≥90

KDIGO 2024 + manufacturer label

Pharmacokineticsplasma · t hours
15minONSET1hPEAK1.9dt½1dDURATION
ONSET
15min · absorption onset
PEAK
1h · Peak plasma concentration
t½
1.9d · 40-50 hours
DURATION
1d · 24-hour estradiol suppression
EXCRETION
Renal (metabolites)
route + CYP
INTERACTIONS
3 major
incl. contraindicated
PREGNANCY
Contraindicated in pregnancy; may cause fetal harm; teratogenic
FDA category + note
Top interactionssee all 10 →
  • Estrogen Containing Products (e.g., Oral Contraceptives, Hormone Replacement Therapy)ContraindicatedDatabase
  • CitalopramSevereDatabaseDDInter
  • ThalidomideSevereDatabaseDDInter
Available in India

167 branded formulations. Look up specific brands in the Drugs workspace.

Jan Aushadhi — generic available at GoI pharmacies

Mechanism

Potent, selective, reversible competitive inhibitor of aromatase (CYP19), the enzyme that converts androgens (androstenedione, testosterone) to estrogens (estrone, estradiol) in peripheral tissues. Reduces circulating estradiol by >95% in postmenopausal women. Does not affect adrenal corticosteroid or aldosterone synthesis.

Indications

Hormone receptor-positive early breast cancer (adjuvant therapy in postmenopausal women)Hormone receptor-positive advanced breast cancer (first-line in postmenopausal women)Ovulation induction (off-label, in PCOS and infertility)Endometriosis (off-label)Gynecomastia in men (off-label)

Dosing

Adult
2.5 mg once daily (fixed dose, no titration needed); continue for 5 years (adjuvant) or until disease progression (advanced)
Pediatric
Not recommended in children
Renal adjustment
No adjustment needed; minimal renal excretion
Hepatic adjustment
Mild–moderate: no adjustment. Cirrhosis / severe hepatic impairment: reduce dose by 50% (FDA §2.5) — not 'not recommended'.
Geriatric
Standard dosing (2.5 mg OD); no adjustment needed based on age
Max dose
2.5 mg/day

Pharmacokinetics

Onset
Days (estradiol suppression begins within hours)
Peak effect
1 hour (Tmax); estradiol suppression >95% within 2-3 days
Duration
24 hours
Half-life
2 days (40-50 hours)
Bioavailability
99.9%
Protein binding
60% (weakly bound to albumin)
Metabolism
Hepatic CYP2A6 (major) and CYP3A4; glucuronidation to inactive metabolite
Excretion
Renal (majority, as metabolites); fecal (minor)

Contraindications

  • Hypersensitivity to letrozole
  • Premenopausal women (unless ovarian function suppressed with GnRH agonist)
  • Pregnancy and breastfeeding
  • Severe hepatic impairment

Side effects

Common
Hot flashesArthralgia / myalgiaFatigueHeadacheNauseaOsteoporosis / bone lossIncreased cholesterolSweatingInsomnia
Serious
  • Osteoporosis and fractures
  • Cardiovascular events (increased risk in some studies)
  • Hypercholesterolemia
  • Hepatotoxicity (rare)
  • Severe allergic reactions (rare)
  • Endometrial thickening (rare, less than tamoxifen)

Pregnancy & lactation

Pregnancy

Contraindicated in pregnancy; may cause fetal harm; teratogenic

Lactation

Contraindicated during breastfeeding

Drug interactions

Estrogen Containing Products (e.g., Oral Contraceptives, Hormone Replacement Therapy)
Contraindicated
Database

Complete loss of therapeutic effect of letrozole, leading to uncontrolled breast cancer progression.

Absolutely contraindicated. Patients must discontinue all estrogen-containing medications before starting letrozole. Ensure no concurrent use.

Citalopram
Severe
Database

Drug interaction classified as: metabolism.

Source: DDInter

Thalidomide
Severe
Database

Clinical effect not specified

Source: DDInter

Carbamazepine
Moderate
Database

Decreased plasma concentrations and reduced efficacy of letrozole due to increased metabolism.

Avoid concomitant use if possible. If co-administration is necessary, monitor for reduced efficacy of letrozole and consider alternative antiepileptic drugs. Dose adjustment of letrozole is not typically recommended based on current data, but close monitoring for disease progression is crucial.

Clomiphene
Moderate
Database

Increased risk of ovarian hyperstimulation syndrome (OHSS) and multiple gestations due to additive or synergistic effects on ovulation induction. Both drugs are used to stimulate ovulation.

Concurrent use is generally not recommended due to increased risk of OHSS and multiple gestations. If sequential use is considered, ensure adequate washout period and careful monitoring of ovarian response.

Estrogens
Moderate
Database

Pharmacologic antagonism; estrogens counteract letrozole effect

Avoid concurrent use

Source: Kimi deep-research + Cla

Phenobarbital
Moderate
Database

Decreased plasma concentrations and reduced efficacy of letrozole due to increased metabolism.

Avoid concomitant use if possible. If co-administration is necessary, monitor for reduced efficacy of letrozole and consider alternative antiepileptic drugs. Dose adjustment of letrozole is not typically recommended based on current data, but close monitoring for disease progression is crucial.

Source: DDInter

Phenytoin
Moderate
Database

Decreased plasma concentrations and reduced efficacy of letrozole due to increased metabolism.

Avoid concomitant use if possible. If co-administration is necessary, monitor for reduced efficacy of letrozole and consider alternative antiepileptic drugs. Dose adjustment of letrozole is not typically recommended based on current data, but close monitoring for disease progression is crucial.

Rifampicin
Moderate
Database

Decreased plasma concentrations and reduced efficacy of letrozole due to increased metabolism.

Avoid concomitant use if possible. If co-administration is necessary, monitor for reduced efficacy of letrozole and consider alternative antitubercular drugs. Dose adjustment of letrozole is not typically recommended based on current data, but close monitoring for disease progression is crucial.

Tamoxifen
Moderate
Database

Letrozole and tamoxifen should not be used together; sequential therapy (letrozole after tamoxifen) is standard

Do not combine; if switching, allow washout period

Source: Kimi deep-research + Cla

2 additional low-confidence interactions hidden — those rows lack a documented mechanism or management plan in our sources.

Related guidelines

Breast cancer
ICMR · Oncology · 2022
Breast cancer
ESMO · Oncology · 2024
Cervical cancer screening and management
ICMR · Oncology · 2022
Tobacco-related cancer prevention
ICMR · Oncology · 2021
Induction of labour
FOGSI · Obstetrics & Gynaecology · 2019

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Sources: KD Tripathi 7e, Goodman & Gilman 14e, Harrison 22e, Katzung·Verified: 2026-05-19 · House clinical team·Cockpit curated: 2026-05-19