Brands, Medical Use, Clinical Data
Brands / Synonyms
Aromasin; Exemestance; Exemestane [Inn]; Exemestane [Usan:Inn:Ban]; Exemestano [Inn-Spanish]; Exemestanum [Inn-Latin]
For the treatment of advanced breast cancer in postmenopausal women whose disease has progressed following tamoxifen therapy.
Aromatase is an enzyme that converts hormones to estrogen in the body's adrenal glands. The aromatase inhibitors (AIs) are drugs that reduce estrogen levels by blocking the action of aromatase in the adrenal glands. The selective AIs (SAIs) selectively reduce levels of estrogen without interfering with levels of other steroid hormones that are produced by the adrenal gland. Drugs in this class include anastrozole (Arimidex ™), letrozole (Femara ™) and exemestane (Aromasin ™).
Mechanism of Action
Breast cancer cell growth may be estrogen-dependent. Aromatase (exemestane) is the principal enzyme that converts androgens to estrogens both in pre- and postmenopausal women. While the main source of estrogen (primarily estradiol) is the ovary in premenopausal women, the principal source of circulating estrogens in postmenopausal women is from conversion of adrenal and ovarian androgens (androstenedione and testosterone) to estrogens (estrone and estradiol) by the aromatase enzyme in peripheral tissues. Estrogen deprivation through aromatase inhibition is an effective and selective treatment for some postmenopausal patients with hormone-dependent breast cancer. Exemestane is an irreversible, steroidal aromatase inactivator, structurally related to the natural substrate androstenedione. It acts as a false substrate for the aromatase enzyme, and is processed to an intermediate that binds irreversibly to the active site of the enzyme causing its inactivation, an effect also known as "suicide inhibition". Exemestane significantly lowers circulating estrogen concentrations in postmenopausal women, but has no detectable effect on adrenal biosynthesis of corticosteroids or aldosterone. Exemestane has no effect on other enzymes involved in the steroidogenic pathway up to a concentration at least 600 times higher than that inhibiting the aromatase enzyme.
Biotrnasformation / Drug Metabolism
AROMASIN Tablets are contraindicated in patients with a known hypersensitivity to the drug or to any of the
Exemestane is extensively metabolized by CYP 3A4, but coadministration of ketoconazole, a potent inhibitor of CYP
3A4, has no significant effect on exemestane pharmacokinetics. Significant pharmacokinetic interactions mediated by
inhibition of CYP isoenzymes therefore appear unlikely. Co-medications that induce CYP 3A4 (e.g., rifampicin,
phenytoin, carbamazepine, phenobarbital, or St. Johnís wort) may significantly decrease exposure to
exemestane. Dose modification is recommended for patients who are also receiving a potent CYP 3A4 inducer (see
DOSAGE AND ADMINISTRATION and CLINICAL
Drug/Laboratory Tests Interactions
No clinically relevant changes in the results of clinical laboratory tests have been observed.