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Letrozole is a potent, nonsteroidal aromatase inhibitor that reduces estrogen biosynthesis by competitively inhibiting the aromatase enzyme. This deprives estrogen-dependent breast cancer cells of their growth stimulus.
- In Postmenopausal Women: Estrogens are synthesized by aromatase converting adrenal androgens (androstenedione, testosterone) to estrone (E1) and estradiol (E2). Letrozole effectively suppresses estrogen levels without affecting androgen levels.
- Suppression Rates: Single doses (0.1–2.5 mg) suppress serum estrone and estradiol by 75–78%, achieving maximum suppression within 48–78 hours.
Pharmacokinetics:
- Absorption: Rapid, complete absorption (bioavailability ~99.9%). Food delays absorption slightly without affecting clinical relevance.
- Protein Binding: ~60% (primarily to albumin).
- Metabolism: Converted to an inactive carbinol metabolite primarily by CYP3A4 and CYP2A6.
- Half-Life: ~2 days.
- Steady State: Achieved within 2–6 weeks of daily 2.5 mg administration.
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✔️ Side Effects of Letrozol 2.5
Common:
- Hot flashes, hypercholesterolemia, fatigue, sweating, arthralgia, rash, headache, dizziness, malaise.
- Gastrointestinal disturbances: nausea, vomiting, constipation, diarrhea, abdominal pain.
- Musculoskeletal issues: osteoporosis, joint pain/stiffness, fractures.
- Edema, depression, weight gain, hypertension, vaginal bleeding.
Rare:
- Anxiety, insomnia, memory issues, somnolence, blurred vision, skin irritation, carpal tunnel syndrome, urinary tract infections, and increased liver enzymes.
✔️ Dosage & Administration of Letrozol 2.5
Adults and Elderly:
- Standard Dose: 2.5 mg once daily.
- Adjuvant/Extended Therapy: Continue for 5 years or until tumor relapse.
- Metastatic Disease: Continue until tumor progression.
Hepatic/Renal Impairment:
- No dosage adjustment is required for moderate hepatic or renal impairment (creatinine clearance ≥10 mL/min).
- Patients with severe hepatic impairment (Child-Pugh score C) require close monitoring.
Children: Not applicable.
✔️ Interaction
- Co-administration with cimetidine or warfarin does not result in clinically significant interactions.
- Letrozole is metabolized by CYP3A4 and CYP2A6, but inhibitors of these enzymes have not shown significant interactions.
✔️ Contraindications
- Hypersensitivity to Letrozole or other aromatase inhibitors.
- Pregnancy, lactation, and premenopausal women.
- Severe hepatic dysfunction.
✔️ Overdose Effects of Letrozol 2.5
- Clinical Experience: Limited data on overdosage.
- Management: Supportive care, monitoring of vital signs, and emesis induction if alert. Dialysis may be considered due to low protein binding.
✔️ Pregnancy & Lactation
- Pregnancy: Category X. Studies in animals indicate teratogenic effects and fetal toxicity. Use in pregnant women is contraindicated.
- Lactation: It is unknown if letrozole is excreted in breast milk. Due to potential adverse effects on the infant, nursing is contraindicated during therapy.
✔️ Precautions & Warnings
- Hepatic Impairment: Exercise caution in patients with moderate hepatic dysfunction.
- Renal Impairment: No dose adjustment is needed for creatinine clearance ≥10 mL/min.
- Driving/Operating Machinery: Fatigue and dizziness may impair abilities; patients should be warned.
✔️ Storage Conditions
Store below 30°C, away from light and moisture. Keep out of reach of children.
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