Exemestane

• Approved Indications:
• Adjuvant treatment of estrogen receptor (ER)-positive early breast cancer in postmenopausal women, typically after 2 to 3 years of tamoxifen therapy.
• Treatment of advanced or metastatic breast cancer in postmenopausal women with disease progression following antiestrogen therapy.
• First-line treatment of advanced breast cancer in postmenopausal women with hormone receptor-positive tumors.
• Off-label / Clinically Accepted Uses:
• Used in combination therapy for hormone receptor-positive breast cancer.
• Occasionally used in fertility treatment to induce ovulation in women with polycystic ovary syndrome (PCOS), though not officially approved for this use.
• Management of hormone-sensitive gynecological disorders in postmenopausal women.

• Route: Oral.
• Adult (Postmenopausal Women):
• Standard dose: 25 mg once daily after a meal.
• Continue daily until disease progression or unacceptable toxicity.
• Pediatrics: Safety and efficacy not established.
• Elderly: No dose adjustment necessary.
• Special Populations:
• Renal impairment: No dose adjustment needed.
• Hepatic impairment: Use caution in moderate to severe hepatic impairment; no formal dose adjustment guidelines.
• Administration:
• Take orally with food to improve absorption.
• Tablets should be swallowed whole with water.
• Missed Dose: Take as soon as remembered unless it is near the time of the next dose. Do not double the dose.

Exemestane is a steroidal irreversible aromatase inhibitor that selectively binds to and permanently inactivates the aromatase enzyme, which catalyzes the conversion of androgens to estrogens in peripheral tissues. By irreversibly inhibiting aromatase, exemestane drastically reduces circulating estrogen levels in postmenopausal women, decreasing estrogen stimulation of hormone receptor-positive breast cancer cells, thereby inhibiting tumor growth and proliferation.

• Absorption: Rapidly absorbed with peak plasma concentration (Cmax) achieved within 2 hours post-dose.
• Bioavailability: Approximately 42%; enhanced when taken with food.
• Distribution: Highly protein bound (~90%) primarily to albumin.
• Metabolism: Extensively metabolized in the liver mainly by CYP3A4 to inactive metabolites.
• Half-life: Approximately 24 hours, allowing once-daily dosing.
• Elimination: Primarily excreted via urine (approximately 90%) mostly as metabolites; small amount excreted in feces.

• Pregnancy: FDA Category D. Exemestane is contraindicated during pregnancy due to potential harm to the fetus from estrogen suppression.
• Lactation: Unknown if excreted in human milk; breastfeeding is not recommended during treatment because of potential adverse effects on the nursing infant.

• Primary Class: Antineoplastic agent.
• Subclass: Aromatase inhibitor, steroidal.

• Known hypersensitivity to exemestane or any of its excipients.
• Pregnancy or women who may become pregnant during treatment.
• Severe hepatic impairment (use with caution).

• Not effective in premenopausal women due to ovarian estrogen production.
• Risk of osteoporosis and fractures due to lowered estrogen levels; bone density monitoring recommended.
• Possible increased risk of cardiovascular events; assess patient cardiovascular risk prior to and during therapy.
• Monitor liver function during treatment.
• Caution in patients with renal impairment, though dose adjustments are generally not required.
• Avoid use in pregnancy and lactation.
• Inform patients about possible menopausal symptoms (hot flashes, sweating).

• Common:
• Hot flashes
• Fatigue
• Arthralgia and myalgia (joint and muscle pain)
• Nausea and vomiting
• Insomnia
• Increased sweating
• Headache
• Serious (less common):
• Osteoporosis and fractures
• Hypercholesterolemia
• Hepatotoxicity (elevated liver enzymes)
• Allergic reactions including rash and angioedema
• Side effects are generally dose-dependent and tend to occur early during treatment.

• CYP3A4 Inducers (e.g., rifampin, carbamazepine): May reduce plasma levels of exemestane, decreasing efficacy.
• CYP3A4 Inhibitors (e.g., ketoconazole, erythromycin): May increase plasma levels and toxicity risk.
• Hormone replacement therapy or estrogen-containing products may antagonize exemestane effects; concomitant use is not recommended.
• No significant interactions with food, but absorption is improved when taken with meals.

• Updated clinical guidelines emphasize the use of aromatase inhibitors like exemestane as preferred adjuvant therapy for hormone receptor-positive breast cancer in postmenopausal women.
• Recent recommendations encourage regular bone mineral density assessments and prophylactic treatment for osteoporosis in long-term users.
• Newer studies support extended use of exemestane beyond 5 years in select patients to reduce recurrence risk.
• No recent major changes to dosing or contraindications by FDA or EMA.

• Store at 20°C to 25°C (68°F to 77°F).
• Protect from moisture and light.
• Keep tablets in the original container until use.
• Keep out of reach of children.
• Do not freeze.