Exemestane

Pronunciation

(ex e MES tane)

U.S. Brand Names

Aromasin®

Generic Available

Canadian Brand Names

Aromasin®

Use

Treatment of advanced breast cancer in postmenopausal women whose disease has progressed following tamoxifen therapy

Pregnancy Risk Factor

Pregnancy Implications

Exemestane has been associated with prolonged gestation, abnormal or difficult labor, increased resorption, reduced number of live fetuses, decreased fetal weight, and retarded ossification in rats. It is not indicated for premenopausal women, but if exposure occurred during pregnancy, risk to the fetus and potential risk for loss of the pregnancy should be discussed.

Lactation

Excretion in breast milk unknown/use caution

Contraindications

Hypersensitivity to exemestane or any component of the formulation; pregnancy

Warnings/Precautions

Exemestane should not be administered concurrently with estrogen-containing drugs; and is not recommended for use in premenopausal women.

Adverse Reactions

>10%:

Central nervous system: Fatigue (22%), pain (13%), depression (13%), insomnia (11%), anxiety (10%)

Endocrine & metabolic: Hot flashes (13%)

Gastrointestinal: Nausea (18%)

1% to 10%:

Cardiovascular: Edema (7%), hypertension (5%), chest pain

Central nervous system: Dizziness (8%), headache (8%), fever (5%), hypoesthesia, confusion

Dermatologic: Rash, itching, alopecia

Gastrointestinal: Vomiting (7%), abdominal pain (6%), anorexia (6%), constipation (5%), diarrhea (4%), increased appetite (3%), dyspepsia

Genitourinary: Urinary tract infection

Neuromuscular & skeletal: Weakness, paresthesia, pathological fracture, arthralgia

Respiratory: Dyspnea (10%), cough (6%), bronchitis, sinusitis, pharyngitis, rhinitis

Miscellaneous: Influenza-like symptoms (6%), diaphoresis (6%), lymphedema, infection

<1%: GGT increased, transaminases increased

A dose-dependent decrease in sex hormone-binding globulin has been observed with daily doses of 25 mg or more. Serum luteinizing hormone and follicle-stimulating hormone levels have increased with this medicine.

Overdosage/Toxicology

If an overdose should occur, general supportive care would be indicated.

Drug Interactions

Substrate of CYP3A4 (major)

CYP3A4 inducers: May decrease the levels/effects of exemestane. Example inducers include aminoglutethimide, carbamazepine, nafcillin, nevirapine, phenobarbital, phenytoin, and rifamycins. Dosage adjustment required with potent inducers.

Rifampin: May decrease exemestane levels; increased dosage recommended.

Ethanol/Nutrition/Herb Interactions

Food: Plasma levels increased by 40% when exemestane was taken with a fatty meal.

Herb/Nutraceutical: St John's wort may decrease exemestane levels. Avoid black cohosh, dong quai in estrogen-dependent tumors.

Stability

Store at 25°C (77°F)

Mechanism of Action

Exemestane is an irreversible, steroidal aromatase inactivator. It prevents conversion of androgens to estrogens by tying up the enzyme aromatase. In breast cancers where growth is estrogen-dependent, this medicine will lower circulating estrogens.

Pharmacodynamics/Kinetics

Absorption: Rapid and moderate (~42%) following oral administration; absorption increases ~40% following high-fat meal

Distribution: Extensive

Protein binding: 90%, primarily to albumin and 1-acid glycoprotein

Metabolism: Extensively hepatic; oxidation (CYP3A4) of methylene group, reduction of 17-keto group with formation of many secondary metabolites; metabolites are inactive

Half-life elimination: 24 hours

Time to peak: Women with breast cancer: 1.2 hours

Excretion: Urine (<1% as unchanged drug, 39% to 45% as metabolites); feces (36% to 48%)

Dosage

Adults: Oral: 25 mg once daily after a meal

Dosage adjustment with CYP3A4 inducers: 50 mg once daily when used with potent inducers (eg, rifampin, phenytoin)

Dosing adjustment in renal/hepatic impairment: Safety of chronic doses has not been studied

Patient Education

Inform prescriber of all prescriptions, OTC medications, or herbal products you are taking, and any allergies you have. Do not take any new medication during therapy unless approved by prescriber. Take after meals at approximately the same time each day; may cause indigestion (small, frequent meals, and frequent mouth care may reduce GI upset). You may be more susceptible to infection (avoid crowds or exposure to infection and do not have any vaccinations unless approved by prescriber). May cause headache, dizziness, confusion, fatigue, anxiety, insomnia (use caution when driving or engaging in tasks requiring alertness until response to medication is known); nausea, vomiting, loss of appetite (small, frequent meals, good mouth care, chewing gum, or sucking hard candy may help); or hot flashes (cool dark room or cold compresses may help). Report chest pain, palpitations; acute headache, visual disturbances; unresolved GI problems; itching or burning on urination, vaginal discharge; acute joint, back, bone, or muscle pain; respiratory difficulty, unusual cough, respiratory infection; or other adverse response. For use in postmenopausal women only.

Nursing Implications

Educate patient about getting blood pressure checked while on medicine, especially if there is a history of poor control. Encourage patient not to drive until she sees how the medicine affects her; it can cause fatigue and dizziness. Medication should be taken at a similar time every day and after a meal to decrease nausea and increase absorption.

Dental Health: Effects on Dental Treatment

No significant effects or complications reported

Dental Health: Vasoconstrictor/Local Anesthetic Precautions

No information available to require special precautions

Mental Health: Effects on Mental Status

Drowsiness, depression, insomnia, and anxiety are common; may cause confusion

Mental Health: Effects on Psychiatric Treatment

None reported

Oncology: Emetic Potential

Low (10% to 30%)

Dosage Forms

Tablet: 25 mg

References

Boeddinghaus IM and Dowsett M, "Comparative Clinical Pharmacology and Pharmacokinetic Interactions of Aromatase Inhibitors," J Steroid Biochem Mol Biol , 2001, 79(1-5):85-91.

Buzdar AU, Robertson JF, Eiermann W, et al, "An Overview of the Pharmacology and Pharmacokinetics of the Newer Generation Aromatase Inhibitors Anastrozole, Letrozole, and Exemestane," Cancer , 2002, 95(9):2006-16.

Lonning PE, "Pharmacological Profiles of Exemestane and Fromestane, Steroidal Aromatase Inhibitors Used for Treatment of Postmenopausal Breast Cancer," Breast Cancer Res Treat , 1998, 49(Suppl 1):45-52.

Lonning PE, Paridaens R, Thurlimann B, et al, "Exemestane Experience in Breast Cancer Treatment," J Steroid Biochem Mol Biol , 1997, 61(3-6):151-5.

Njar VC and Brodie AM, "Comprehensive Pharmacology and Clinical Efficacy of Aromatase Inhibitors," Drugs , 1999, 58(2):233-55.

Scott LJ and Wiseman LR, "Exemestane," Drugs , 1999, 58(4):675-80.

International Brand Names

Aromasil® (ES, PT); Aromasin® (AT, AU, BE, BR, CA, CH, CO, CZ, DE, DK, FI, GB, HR, HU, ID, IE, IL, IT, NL, NO, NZ, PL, RO, SE, SG, SI, TH, YU); Aromasine® (AT, FR)

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