AROMEX

Exemestane is an oral steroidal aromatase inhibitor used in the adjuvant treatment of hormonally-responsive (also called hormone-receptor-positive, estrogen-responsive) breast cancer in postmenopausal women.

It irreversibly binds to the active site of the enzyme resulting in permanent inhibition.

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 ™).

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Clinical trials have been conducted with exemestane given as a single dose to healthy female volunteers at doses as high as 800 mg and daily for 12 weeks to postmenopausal women with advanced breast cancer at doses as high as 600 mg. These dosages were well tolerated.

There is no specific antidote to overdosage and treatment must be symptomatic.

General supportive care, including frequent monitoring of vital signs and close observation of the patient, is indicated.

A male child (age unknown) accidentally ingested a 25-mg tablet of exemestane.

The initial physical examination was normal, but blood tests performed 1 hour after ingestion indicated leucocytosis (WBC 25000/mm with 90% neutrophils).

Blood tests were repeated 4 days after the incident and were normal.

No treatment was given.

In mice, mortality was observed after a single oral dose of exemestane of 3200 mg/kg, the lowest dose tested (about 640 times the recommended human dose on a mg/m 2 basis).

In rats and dogs, mortality was observed after single oral doses of exemestane of 5000 mg/kg (about 2000 times the recommended human dose on a mg/m 2 basis) and of 3000 mg/kg (about 4000 times the recommended human dose on a mg/m 2 basis), respectively.

Convulsions were observed after single doses of exemestane of 400 mg/kg and 3000 mg/kg in mice and dogs (approximately and 4000 times the recommended human dose on a mg/m 2 basis), respectively.

Exemestane tablets are contraindicated in patients with a known hypersensitivity to the drug or to any of the excipients.

Patients with a known hypersensitivity to the drug or to any of the excipients.

One 25 mg tablet once daily after a meal. 2.1 Recommended Dose The recommended dose of exemestane tablets in early and advanced breast cancer is one 25 mg tablet once daily after a meal. adjuvant treatment of postmenopausal women with estrogen-receptor positive early breast cancer who have received two to three years of tamoxifen and are switched to exemestane tablets for completion of a total of five consecutive years of adjuvant hormonal therapy. the treatment of advanced breast cancer in postmenopausal women whose disease has progressed following tamoxifen therapy. 2.2 Dose Modifications Concomitant use of strong CYP 3A4 inducers decreases exemestane exposure.

For patients receiving exemestane tablets with a strong CYP 3A4 inducer such as rifampicin or phenytoin, the recommended dose of exemestane tablets is 50 mg once daily after a meal.

Exemestane tablets are

White colored, round, biconvex, film-coated tablets debossed with "X" on one side and "1" on other side.

Each tablet contains 25 mg of exemestane.

Exemestane tablets are packaged in

HDPE bottles with a child-resistant screw cap, supplied in bottles of 30 tablets. 30-tablet HDPE bottle NDC 63629-2056-1.

Store at 25°C (77°F); excursions permitted to 15°–30°C (59°–86°F) .

Repackaged/Relabeled by: Bryant Ranch Prepack, Inc.

Burbank, CA 91504.

Based on findings in animal studies and its mechanism of action, exemestane tablets can cause fetal harm when administered to a pregnant woman.

Limited human data from case reports are insufficient to inform a drug-associated risk.

In animal reproduction studies, administration of exemestane to pregnant rats and rabbits caused increased incidence of abortions, embryo-fetal toxicity, and prolonged gestation with abnormal or difficult labor.

Advise pregnant women of the potential risk to a fetus.

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown.

In the

US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

In animal reproduction studies in rats and rabbits, exemestane caused embryo-fetal toxicity, and was abortifacient.

Radioactivity related to 14 C-exemestane crossed the placenta of rats following oral administration of 1 mg/kg exemestane.

The concentration of exemestane and its metabolites was approximately equivalent in maternal and fetal blood.

When rats were administered exemestane from 14 days prior to mating until either days 15 or of gestation, and resuming for the 21 days of lactation, an increase in placental weight was seen at 4 mg/kg/day (approximately 1.5 times the recommended human daily dose on a mg/m 2 basis).

Increased resorptions, reduced number of live fetuses, decreased fetal weight, retarded ossification, prolonged gestation and abnormal or difficult labor was observed at doses equal to or greater than 20 mg/kg/day (approximately 7.5 times the recommended human daily dose on a mg/m 2 basis).

Daily doses of exemestane, given to rabbits during organogenesis, caused a decrease in placental weight at 90 mg/kg/day (approximately 70 times the recommended human daily dose on a mg/m 2 basis) and in the presence of maternal toxicity, abortions, an increase in resorptions, and a reduction in fetal body weight were seen at 270 mg/kg/day. No malformations were noted when exemestane was administered to pregnant rats or rabbits during the organogenesis period at doses up to and 270 mg/kg/day, respectively (approximately and 210 times the recommended human dose on a mg/m 2 basis, respectively).

Safety and effectiveness in pediatric patients have not been established.