Exemestane (Aromasin) — Clinical FAQs

Question 1

What is Exemestane FDA-approved to treat?

Accepted Answer

Exemestane is FDA-approved for the following oncology indications: 1. Postmenopausal women with early HR-positive breast cancer — adjuvant therapy for 2–3 years after completing 2–3 years of tamoxifen (sequential strategy completing a total of 5 years; IES trial: 32% relative reduction in contralateral breast cancer and recurrence risk) 2. Postmenopausal women with advanced HR-positive breast cancer — after failure of tamoxifen therapy (FDA approved 1999) 3. Advanced HR-positive, HER2-negative breast cancer in combination with everolimus — after progression on anastrozole or letrozole (FDA approved 2012; BOLERO-2 trial: PFS HR 0.45).

Question 2

How does Exemestane work (mechanism of action)?

Accepted Answer

Steroidal aromatase inactivator (type I aromatase inhibitor; also termed a "mechanism-based" or "suicide" inhibitor). Exemestane is structurally similar to the natural aromatase substrate androstenedione. It acts as a false substrate, irreversibly binding to the active site of aromatase (CYP19A1) and covalently inactivating the enzyme, preventing its subsequent participation in estrogen synthesis. This mechanism distinguishes exemestane from non-steroidal AIs (letrozole, anastrozole), which are reversible competitive inhibitors. Enzyme activity can only be restored by synthesis of new aromatase protein, leading to sustained, durable estrogen suppression (>95% reduction in circulating estradiol). An active metabolite (17-hydroexemestane) weakly stimulates the androgen receptor, which may confer modest bone-protective effects distinct from non-steroidal AIs.

Question 3

How is Exemestane administered?

Accepted Answer

Exemestane is administered Oral (PO). Administer 25 mg orally once daily after a meal (food increases AUC by ~40% and reduces variability).

Question 4

What are the most common side effects of Exemestane?

Accepted Answer

The most commonly reported side effects of Exemestane (≥10% incidence) include: Hot flashes (13–22%), Arthralgia / joint stiffness (15–29%), Fatigue (22%), Nausea (9–18%), Depression / mood changes and others (10 total). Consult your oncologist for complete prescribing information.

Question 5

Is Exemestane safe during pregnancy?

Accepted Answer

Exemestane pregnancy safety: Category X — contraindicated in pregnant women. Exemestane causes fetal harm based on mechanism of action; premenopausal females of reproductive potential must use effective non-hormonal contraception during therapy.. Oncologists should review the complete prescribing information and discuss reproductive risks with patients before initiating therapy.

Exemestane — Drug Monograph

Mechanism of Action

FDA Indications

Common Side Effects

Clinical Pearl

Related Therapies & Mechanisms