Introduction
Exemestane is an oral steroidal aromatase inactivator used in the treatment of hormone receptor-positive breast cancer in postmenopausal women. It belongs to the class of drugs known as aromatase inhibitors, which play a crucial role in endocrine therapy for breast cancer by reducing estrogen production.
Mechanism of Action
Exemestane acts as an irreversible, steroidal aromatase inactivator. It binds permanently to the aromatase enzyme, which is responsible for converting androgens (particularly androstenedione and testosterone) into estrogens (estrone and estradiol) in peripheral tissues. This irreversible inhibition results in a significant reduction (up to 95%) of circulating estrogen levels in postmenopausal women, thereby depriving estrogen-dependent breast cancer cells of the hormonal stimulation needed for growth.
Indications
- Adjuvant treatment of postmenopausal women with estrogen-receptor positive early breast cancer who have received 2-3 years of tamoxifen and are switched to exemestane for completion of a total of 5 years of adjuvant hormonal therapy
- Treatment of advanced breast cancer in postmenopausal women whose disease has progressed following tamoxifen therapy
Dosage and Administration
Standard dosing: 25 mg orally once daily after a meal Duration: Continue until disease progression or completion of adjuvant therapy Special populations:- Renal impairment: No dosage adjustment necessary
- Hepatic impairment: Mild to moderate impairment (Child-Pugh A-B) requires no adjustment; use caution in severe impairment (Child-Pugh C)
- Geriatric patients: No dosage adjustment required
- Premenopausal women: Not recommended (may not effectively suppress estrogen)
Pharmacokinetics
Absorption: Well absorbed from the GI tract; bioavailability is approximately 42% due to first-pass metabolism Distribution: Extensive tissue distribution; 90% bound to plasma proteins Metabolism: Extensive hepatic metabolism primarily via CYP3A4; also undergoes reduction by aldoketoreductases Elimination: Excreted equally in urine and feces; terminal elimination half-life is approximately 24 hoursContraindications
- Hypersensitivity to exemestane or any component of the formulation
- Premenopausal women
- Pregnancy or breastfeeding
- Concomitant use with estrogen-containing medications
Warnings and Precautions
- Bone effects: Accelerates bone loss; monitor bone mineral density and consider calcium/vitamin D supplementation and bisphosphonate therapy
- Cardiovascular effects: May increase cardiovascular events; monitor blood pressure and lipid profile
- Hepatic impairment: Use with caution in patients with severe hepatic impairment
- Corticosteroid replacement: May interfere with corticosteroid replacement therapy in patients with pre-existing adrenal insufficiency
Drug Interactions
- Estrogen-containing therapies: May interfere with exemestane's action
- CYP3A4 inducers (e.g., rifampin, phenytoin, St. John's wort): May decrease exemestane concentrations
- CYP3A4 inhibitors (e.g., ketoconazole, erythromycin): May increase exemestane concentrations
- Tamoxifen: Concurrent use not recommended (may reduce exemestane concentrations)
Adverse Effects
Common (≥10%):- Hot flashes (13-28%)
- Fatigue (8-22%)
- Arthralgia (15-29%)
- Headache (10-15%)
- Insomnia (11-14%)
- Increased sweating (6-12%)
- Hypertension (5-13%)
- Osteoporosis and fractures
- Cardiovascular events (myocardial infarction, angina, heart failure)
- Hepatic toxicity
- Depression
Monitoring Parameters
- Bone mineral density at baseline and periodically during treatment
- Lipid profile at baseline and periodically
- Liver function tests regularly
- Blood pressure monitoring
- Signs and symptoms of disease progression
- Assessment of menopausal status in perimenopausal women
- Monitoring for arthralgia and musculoskeletal symptoms
Patient Education
- Take medication at the same time each day, preferably after a meal
- Do not take estrogen-containing medications or supplements
- Report persistent hot flashes, joint pain, or mood changes
- Maintain adequate calcium and vitamin D intake
- Engage in regular weight-bearing exercise to maintain bone health
- Report any new pain, especially in bones
- Use effective non-hormonal contraception if sexually active
- Attend all scheduled follow-up appointments and screenings
- Be aware of potential for fatigue and adjust activities accordingly
References
1. National Comprehensive Cancer Network (NCCN) Guidelines: Breast Cancer Version 4.2023 2. Pfizer Inc. Aromasin® (exemestane) prescribing information. 2022 3. Coombes RC, et al. A randomized trial of exemestane after two to three years of tamoxifen therapy in postmenopausal women with primary breast cancer. N Engl J Med. 2004;350(11):1081-1092 4. Paridaens R, et al. Phase III study comparing exemestane with tamoxifen as first-line hormonal treatment of metastatic breast cancer in postmenopausal women. J Clin Oncol. 2008;26(30):4883-4890 5. Lonning PE, et al. Effects of exemestane administered for 2 years versus placebo on bone mineral density, bone biomarkers, and plasma lipids in patients with surgically resected early breast cancer. J Clin Oncol. 2005;23(22):5126-5137 6. Micromedex® Solutions: Exemestane Drug Information. Truven Health Analytics