Exemestane Advanced Drug Monograph

Exemestane Report

Name: Exemestane Name (English): Exemestane DrugBank ID: DB00990 Type: Small Molecule CAS Number: 107868-30-4

Exemestane is an irreversible, steroidal aromatase inhibitor. It is indicated for the adjuvant treatment of postmenopausal women with estrogen receptor-positive early breast cancer and for the treatment of advanced breast cancer in postmenopausal women whose disease has progressed following anti-estrogen therapy. Exemestane works by binding to and inactivating the aromatase enzyme, which is responsible for the final step in estrogen biosynthesis. This leads to a significant reduction in circulating estrogen levels.

Pharmacokinetics: Exemestane is rapidly absorbed after oral administration, with peak plasma concentrations reached within 2 hours. It is extensively metabolized in the liver, primarily via CYP3A4, and the metabolites are excreted in both urine and feces. The elimination half-life is approximately 9 hours. Food can increase the extent of absorption.

Mechanism of Action: Exemestane is a steroidal aromatase inhibitor. It acts as a false substrate for the aromatase enzyme, leading to its irreversible inactivation. By inhibiting aromatase, exemestane reduces the production of estrogen in postmenopausal women, where the primary source of estrogen is the conversion of androgens to estrogens by aromatase in peripheral tissues.

Indications:

• Adjuvant treatment of postmenopausal women with estrogen receptor-positive early breast cancer, either as initial adjuvant therapy or following 2-3 years of tamoxifen. It is also indicated for extending adjuvant treatment in women who have received 5 years of tamoxifen.
• Treatment of advanced breast cancer in postmenopausal women whose disease has progressed following anti-estrogen therapy. Efficacy has not been demonstrated in patients with estrogen receptor-negative status.

Dosage and Administration: The recommended dose is 25 mg orally once daily, preferably after a meal.

Adverse Effects: Common adverse effects include hot flushes, fatigue, arthralgia, nausea, headache, and insomnia. Exemestane can also lead to decreased bone mineral density and an increased risk of fractures. Less common but more serious side effects may include elevated liver enzymes.

Contraindications: Exemestane is contraindicated in premenopausal women, during pregnancy, and during lactation. It is also contraindicated in patients with known hypersensitivity to exemestane or any of its excipients.

Drug Interactions: Caution should be exercised when administering exemestane with drugs that induce CYP3A4, as this may decrease exemestane exposure. Drugs that inhibit CYP3A4 may increase exemestane exposure.

Precautions: Bone mineral density should be assessed prior to and periodically during treatment. Patients at risk of osteoporosis should be managed appropriately. Hepatic or renal insufficiency can lead to increased exemestane levels.

This report provides a summary of information about Exemestane and should not be considered a substitute for professional medical advice. Always consult with a healthcare provider for any questions or concerns regarding this medication.