Aromasin – Hormonal Therapy for Postmenopausal Breast Cancer

Aromasin (exemestane) is an oral hormonal medicine prescribed for postmenopausal women with estrogen-receptor positive breast cancer. It is used to complete a full five-year course of adjuvant therapy following initial treatment with tamoxifen, as well as to treat advanced breast cancer that has progressed after tamoxifen therapy.

• Adjuvant treatment of postmenopausal women with estrogen-receptor positive early breast cancer who have completed 2 to 3 years of tamoxifen therapy, to complete a total of 5 years of hormonal therapy.
• Treatment of advanced breast cancer in postmenopausal women whose disease has progressed following tamoxifen therapy.

Exemestane

Exemestane irreversibly inhibits the aromatase enzyme responsible for converting androgens into estrogens in peripheral tissues. By blocking this conversion, it reduces circulating estrogen levels, which can stimulate hormone-dependent breast cancer growth. Exemestane acts as a false substrate, binding irreversibly to aromatase and inactivating it, a process known as "suicide inhibition." It selectively lowers estrogen in postmenopausal women without affecting adrenal corticosteroid production.

Adults: The recommended dose is 25 mg taken orally once daily. The tablets can be taken with or without food; however, a high-fat meal may increase absorption by approximately 40%. Patients are to continue treatment for the prescribed duration, typically to complete five years of adjuvant therapy when switched from tamoxifen or as directed for advanced disease.

Special populations: No specific dose adjustment is established, but patients with moderate or severe hepatic or renal impairment have increased drug exposure (approximately threefold). Careful monitoring is advised; dosage adjustment is not routinely recommended.

Missed dose: No specific instructions provided.

Hypersensitivity to exemestane or any of the excipients. Use in premenopausal women is contraindicated. Aromasin is contraindicated in pregnancy.

• May cause fetal harm if administered during pregnancy. Aromasin is contraindicated in pregnant women and should only be used in postmenopausal women.
• Do not administer to premenopausal women.
• Co-administration with estrogen-containing agents is contraindicated as it may reduce drug efficacy.
• Use with caution in patients with moderate to severe hepatic or renal impairment due to increased drug exposure; safety for chronic use in these populations is not established.

In clinical studies, the most notable blood-related laboratory changes included lymphocytopenia (grade 3 or 4 in approximately 20% of advanced breast cancer patients, often with pre-existing lower-grade lymphopenia). Elevations in liver enzymes such as gamma glutamyl transferase and bilirubin were also reported, mostly related to underlying disease. Aromasin treatment led to reductions in bone mineral density over time. Plasma HDL cholesterol decreased by 6-9%, while total cholesterol, LDL, and other lipid parameters remained unchanged. Other reported effects include mild elevations in homocysteine levels.

• Potent CYP3A4 inducers (e.g., rifampicin, phenytoin, carbamazepine, phenobarbital, St. John's wort) can significantly decrease exemestane levels; dose modification is recommended in such cases.
• Co-administration with CYP3A4 inhibitors (e.g., ketoconazole) does not significantly affect exemestane pharmacokinetics.

Pregnancy: Aromasin is contraindicated and not studied in pregnant women. Animal studies showed fetal harm and pregnancy complications at doses above the recommended human exposure. Women exposed during pregnancy should be informed of potential fetal risks.

Lactation: No human data available. Aromasin is intended for postmenopausal women; breastfeeding is not applicable.