Letrozole

🔹 1. Basic Information

Generic name: Letrozole
Brand name: Femara
Drug class: Aromatase inhibitor (endocrine therapy)
Formulation: Film-coated tablet
Strength: 2.5 mg letrozole per tablet
Mechanism of Action:
Blocks aromatase enzyme → reduces estrogen production → inhibits growth of estrogen-dependent breast cancer cells.

🔹 2. Indications

Postmenopausal women:

• Early breast cancer:

  • Adjuvant treatment following surgery, or after 5 years of tamoxifen therapy.

• Advanced/metastatic breast cancer:

  • First-line or continued therapy for hormone receptor-positive disease.

• Neoadjuvant use:

  • When surgery is not immediately suitable.

• Prevention of recurrence or metastasis in estrogen receptor–positive cases.

🔹 3. Dosing & Administration

Dose: 2.5 mg orally once daily.
Route: Oral (with or without food).
Duration: Continue daily as prescribed; long-term maintenance often required.
Missed dose: Take as soon as remembered unless next dose is due within 2–3 hours.
Overdose: Seek medical attention; supportive management.
Do not stop therapy unless directed by a doctor.

🔹 4. Dose Modifications

• No standard dose adjustments; use with caution in severe hepatic or renal impairment.

• Monitor bone density and lipid profile during prolonged use.

• Therapy individualized based on tolerance and response.

🔹 5. Co-medications / Drug Interactions

Avoid with:

• CYP3A4/2A6 inhibitors: Ketoconazole, itraconazole, voriconazole, ritonavir, clarithromycin, telithromycin → ↑ FEMARA levels.

• CYP inducers: Rifampicin, carbamazepine, phenytoin, phenobarbital, St John’s Wort → ↓ FEMARA levels.

• Tamoxifen: Reduces letrozole plasma concentration.
  Contraception: Non-hormonal contraception may be required during early menopause transition.

🔹 6. Contraindications

• Premenopausal status (active menstruation).

• Pregnancy and breastfeeding.

• Severe hepatic or renal impairment.

• Hypersensitivity to letrozole or excipients.

• Lactose intolerance (contains lactose).

🔹 7. Monitoring Requirements

• Bone density: Risk of osteoporosis → periodic DEXA scans.

• Lipids: Check cholesterol periodically.

• Hepatic/Renal function: Monitor in at-risk patients.

• Cardiac: Observe for ischemic events or thromboembolism.

• Clinical: Watch for menopausal symptoms, dizziness, or depression.

🔹 8. Side Effects & Management

Serious (stop & seek urgent care):
Stroke, myocardial infarction, thromboembolism (DVT/PE), allergic reaction, hepatitis, severe rash (Stevens-Johnson), severe infection (neutropenia).

Very common (>10%):
Hot flushes, hypercholesterolemia, increased sweating, fatigue, arthralgia/bone pain.
→ Manage symptomatically; monitor cholesterol and bone health.

Common (1–10%):
Headache, dizziness, nausea, constipation/diarrhoea, appetite changes, depression, edema, weight gain, hair thinning, hypertension, vaginal bleeding or dryness, back pain, rash.

Less common (<1%):
Insomnia, anxiety, carpal tunnel syndrome, cataract/blurred vision, jaundice, urinary tract infection, skin reactions.

🔹 9. Use in Special Populations

Pregnancy: Contraindicated — teratogenic risk.
Breastfeeding: Contraindicated.
Fertility: May restore ovulation in perimenopausal women; effective contraception required.
Elderly: No dose adjustment needed.
Children/adolescents: Not indicated.
Hepatic/Renal impairment: Use with caution in severe dysfunction.

🔹 10. Duration of Use / When to Stop

Continue daily until disease recurrence, progression, or completion of prescribed adjuvant course (typically 5 years).
Stop immediately if:

• Pregnancy occurs

• Severe allergic, hepatic, or thrombotic event

• Intolerable adverse effects

https://pi-pil-repository.sahpra.org.za/wp-content/uploads/2022/11/pil-femara-08-Nov-2022.pdf