Femara
Femara
Generic Name
Femara
Mechanism
- Target: Cytochrome P450 aromatase (CYP19A1), the enzyme catalyzing the conversion of androgens to estrogens.
- Binding: Reversibly binds to the heme‑iron center as an irreversible inactivator.
- Outcome: Decreases systemic estrogen levels by 85‑95 %, limiting estrogen‑dependent proliferation of breast cancer cells.
Pharmacokinetics
| Property | Details |
| Absorption | Oral; peak plasma concentration (Cmax) ~2 h after a 1 mg dose. |
| Bioavailability | ~80 % (unchanged by food). |
| Distribution | Low plasma protein binding (~18 %); extensive tissue distribution. |
| Metabolism | Hepatic CYP3A4 and hepatic UGT1A9‑mediated glucuronidation. |
| Elimination | ~85 % as metabolites in feces; ~15 % renal excretion. |
| Half‑life | ~53 h (steady‑state ~1–2 weeks). |
| Drug interactions | Cytochrome inhibitors/inducers (e.g., ketoconazole, rifampin) can respectively increase or reduce exposure. |
Indications
- Post‑menopausal female breast cancer
- Adjuvant therapy after surgery ± radiation for early‑stage, estrogen‑receptor positive disease.
- Extended adjuvant (up to 10 years) past 5 years of tamoxifen.
- Metastatic breast cancer refractory to tamoxifen/letrozole, or as part of second‑line endocrine therapy.
- Pre‑clinical evidence suggests use in male hormone‑responsive breast cancer; not FDA‑approved.
Contraindications
- Contraindications
- Hypersensitivity to anastrozole or any excipients.
- Known estrogen‑dependent gynecologic malignancies (e.g., uterine sarcoma).
- Warnings
- Osteoporosis/osteopenia: chronic estrogen suppression increases bone turnover.
- Severe hepatic impairment: reduced metabolism, increased plasma levels.
- Pregnancy: may cause fetal estrogen deficiency—use only if maternal benefit > risk.
- Bone‑pain or fractures: consider concurrent bone‑sparing therapy.
Dosing
- Standard regimen:
- 1 mg orally once daily, taken at the same time each day.
- Alternative: 0.5 mg daily may be used when tolerability issues arise.
- Initiation: Take on an empty stomach; food does not significantly alter absorption.
- Duration: Typically 5–10 years for adjuvant therapy; until progression for metastatic disease.
- Compliance: Pill‑box reminder and routine pill counts help maintain adherence.
Adverse Effects
| Symptom | Frequency | Notes |
| Hot flashes | 15–30 % | May improve after 6 months; cooling measures or gabapentin may help. |
| Joint pain (arthralgia) | 7–23 % | NSAIDs or analgesics if persistent. |
| Fatigue | 10–15 % | Lifestyle interventions recommended. |
| Nausea, headache, dizziness | <5 % | OTC remedies usually sufficient. |
| Serious | ||
| Osteoporotic fracture | 1–2 % | Baseline DEXA; bisphosphonate or denosumab if T‑score < –1.5. |
| Cardiovascular events | Rare | Monitor ECG when clinically indicated. |
| Abdominal pain, constipation, diarrhea | <3 % | Hydration and fiber. |
Monitoring
- Baseline:
- Blood chemistry (CBC, CMP).
- Bone mineral density (DEXA).
- Calcium & alkaline phosphatase.
- During therapy:
- DEXA every 12–24 months.
- Bone turnover markers (serum CTX, P1NP) annually.
- Liver function tests every 6 months if hepatic impairment present.
- Adverse events:
- Prompt assessment of hot flashes, arthralgia, fractures.
- Evaluate bone‑sparing therapy if indicated.
Clinical Pearls
1. Bone protection is essential: Concomitant bisphosphonate or denosumab is recommended for patients with a baseline DEXA T‑score ≤ –1.5 or osteopenia.
2. Hot flashes can be dose‑shifted: Switching 1 mg to 0.5 mg daily may reduce severity without compromising efficacy.
3. Adjuvant sequencing matters: Post‑tamoxifen, anastrozole improves overall survival better than extended tamoxifen alone.
4. Drug–interaction vigilance: Co‑prescribing strong CYP3A4 inducers (e.g., rifampin) can reduce Femara exposure and undermine efficacy; consider dose adjustment or alternative endocrine therapy.
5. Gender‑specific caution: Though off‑label for males, Femara can precipitate gynecomastia or osteoporosis; use with caution and monitor bone density.
6. Non‑adherence risk: The lack of overt side‑effects in early months can lead to complacency; use patient education and scheduled clinic visits to reinforce daily intake.
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• Key pharmacology terms: aromatase inhibitor, estrogen suppression, post‑menopausal breast cancer, bone mineral density, DEXA, bisphosphonate.