1. Clinical Overview
Anastrozole is a potent, non-steroidal, third-generation aromatase inhibitor used primarily in the adjuvant and metastatic treatment of hormone receptor-positive breast cancer in postmenopausal women. It works by selectively inhibiting the aromatase enzyme, which is responsible for the conversion of androgens (androstenedione and testosterone) to estrogens (estrone and estradiol). This leads to a profound reduction in circulating estrogen levels, depriving estrogen-dependent breast cancer cells of their primary growth stimulus. In the Indian context, it is a cornerstone of endocrine therapy and is widely available across multiple brands.
| Onset | Duration | Bioavailability |
|---|---|---|
| Pharmacological effect begins within hours of administration, with significant suppression of serum estradiol levels (>70%) observed within 24 hours. | The inhibitory effect on aromatase and suppression of plasma estrogen levels is maintained with once-daily dosing. | Approximately 80-85% following oral administration. Food does not significantly affect the extent of absorption. |
2. Mechanism of Action
Anastrozole is a competitive, reversible inhibitor of the aromatase enzyme (cytochrome P450 CYP19). This enzyme complex, located in the endoplasmic reticulum of cells in adipose tissue, liver, breast, and breast cancer tissue, catalyzes the final and rate-limiting step in estrogen biosynthesis: the conversion of androgens (androstenedione and testosterone) to estrogens (estrone and estradiol). By binding to the heme group of the aromatase enzyme, anastrozole prevents the conversion, leading to a profound (≥80%) and sustained reduction in circulating estrogen levels in postmenopausal women.
3. Indications & Uses
- Adjuvant treatment of hormone receptor-positive early breast cancer in postmenopausal women.
- First-line treatment of hormone receptor-positive or hormone receptor-unknown locally advanced or metastatic breast cancer in postmenopausal women.
- Treatment of advanced breast cancer in postmenopausal women with disease progression following tamoxifen therapy.
4. Dosage & Administration
Adult Dosage: 1 mg orally, once daily. Can be taken with or without food, at approximately the same time each day.
Administration: Tablet should be swallowed whole with a glass of water. Treatment duration for adjuvant therapy is typically 5 years, or as determined by the oncologist based on risk assessment. For metastatic disease, treatment continues until disease progression or unacceptable toxicity.
5. Side Effects
Common side effects may include:
- Hot flushes (flashes)
- Asthenia (weakness/fatigue)
- Arthralgia (joint pain) and myalgia (muscle pain)
- Headache
- Nausea
- Mild skin rash
- Increased sweating
- Vaginal dryness
6. Drug Interactions
| Drug | Effect | Severity |
|---|---|---|
| Tamoxifen | Concomitant use reduces anastrozole plasma levels by 27%. It is not recommended as it may reduce anastrozole efficacy. | Major |
| Estrogen-containing therapies (HRT, oral contraceptives) | May counteract the pharmacological effect of anastrozole. Contraindicated. | Major |
| CYP3A4 Inducers (e.g., Rifampicin, Phenytoin, Carbamazepine, St. John's Wort) | May decrease anastrozole plasma concentrations, potentially reducing efficacy. Monitor clinical response. | Moderate |
| CYP3A4 Inhibitors (e.g., Ketoconazole, Itraconazole, Clarithromycin) | May increase anastrozole plasma concentrations. Clinical significance is likely minimal due to wide therapeutic index, but monitor for increased side effects. | Minor |
| Warfarin | Isolated reports of increased INR and bleeding events. Monitor INR closely when anastrozole is initiated or discontinued. | Moderate |
7. Patient Counselling
- DO take the tablet exactly as prescribed by your oncologist, usually once daily.
- DO inform all your doctors and dentists that you are taking anastrozole before any new treatment.
- DO report any new or worsening joint pain, bone pain, or signs of fracture (e.g., sudden back pain) to your doctor.
- DO NOT take if you are pregnant, planning pregnancy, or breastfeeding.
- DO NOT take any estrogen-containing medicines, including hormone replacement therapy (HRT), birth control pills, or herbal supplements like black cohosh, without consulting your oncologist.
- DO NOT stop taking the medicine without discussing with your doctor, even if you feel well.
8. Toxicology & Storage
Overdose: Single doses up to 60 mg have been reported without severe effects. Expected symptoms would be an extension of the pharmacological effect (severe estrogen suppression) and side effects: severe hot flushes, nausea, vomiting, drowsiness, dizziness, and possibly severe arthralgia. No specific antidote.
Storage: Store below 30°C. Protect from light and moisture. Keep the tablet in the original blister pack or container until use. Keep out of reach of children.