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Exemestane

(British Approved Name, US Adopted Name, rINN)

Drug Nomenclature

International Nonproprietary Names (INNs) in main languages (French, Latin, Russian, and Spanish):

ExemestaneSynonyms: Eksemestaani; Exemestan; Exemestano; Exemestanum; FCE-24304
BAN: Exemestane
USAN: Exemestane
INN: Exemestane [rINN (en)]
INN: Exemestano [rINN (es)]
INN: Exémestane [rINN (fr)]
INN: Exemestanum [rINN (la)]
INN: Ексеместан [rINN (ru)]
Chemical name: 6-Methyleneandrosta-1,4-diene-3,17-dione
Molecular formula: C20H24O2 =296.4
CAS: 107868-30-4
ATC code: L02BG06

Adverse Effects and Precautions

The most frequently reported adverse effects for exemestane are gastrointestinal disturbances, hot flushes, arthralgia, myalgia, sweating, fatigue, and dizziness. Other reported effects include headache, insomnia, somnolence, depression, skin rashes, alopecia, asthenia, and peripheral and leg oedema. Thrombocytopenia and leucopenia have been reported occasionally. Reductions in bone mineral density can occur with long-term use of exemestane. Density should therefore be assessed at the start of therapy, in those with osteoporosis or at risk of it, and patients monitored during therapy.

The use of exemestane is contra-indicated in premeno-pausal women (particularly in pregnancy).

Effects on the musculoskeletal system

Exemestane therapy has been found to decrease bone mineral density (BMD) in postmenopausal women with early breast cancer. In one study, the decrease in BMD was seen within 6 months of switching therapy from tamoxifen, and was significant at the lumbar spine and hip. In a Scandinavian study, bone mineral density loss with exemestane compared with placebo was modest from the femoral neck, and not significant at the lumbar spine; however, it was noted that the changes in the placebo group were greater than expected, possibly due to the lack of calcium and vitamin D supplementation, and that there is a high incidence of hip fracture in Scandinavia.

Patients starting exemestane therapy should be assessed for baseline bone mineral density; while those with normal BMD are considered to not need further assessment beyond lifestyle advice, those with osteopenia should have their bone mineral density monitored, and therapeutic interventions made as appropriate.

Interactions

The metabolism of exemestane is mediated by the cytochrome P450 isoenzyme CYP3A4. Rifampicin, a potent inducer of CYP isoenzymes, can decrease plasma concentrations of exemestane. Use with other drugs that induce this isoenzyme may reduce the efficacy of exemestane. Exemestane should also be used cautiously with drugs that are substrates for CYP3A4 and that have a narrow therapeutic index. Significant effects on exemestane clearance by cytochrome P450 isoenzyme inhibitors are considered unlikely. Exemestane should not be given with oestrogen-containing drugs as these would negate its pharmacological action.

Pharmacokinetics

Exemestane is rapidly absorbed from the gastrointestinal tract. Its bioavailability is limited by first-pass metabolism, but is increased when taken with food. Exemestane is widely distributed, and is extensively bound to plasma proteins. It is metabolised via oxidation by the cytochrome P450 isoenzyme CYP3 A4, and via reduction by aldoketoreductase. Metabolites are excreted in the urine and faeces, and less than 1% of a dose is excreted unchanged in the urine. Exemestane has a terminal elimination half-life of about 24 hours.

ExemestaneUses and Administration

Exemestane is a selective inhibitor of the aromatase (oestrogen synthase) system, similar to formestane. It is used in the treatment of advanced breast cancer, in postmenopausal women who are no longer responsive to antioestrogen therapy. It is also used for adjuvant treatment of postmenopausal women with oestrogen-receptor positive early breast cancer, after 2 to 3 years of initial adjuvant tamoxifen treatment; a total of 5 years of adjuvant hormonal therapy should be given.

The recommended oral dose is 25 mg once daily, preferably after a meal. In patients receiving potent inducers of the cytochrome P450 isoenzyme CYP3A4 (such as rifampicin or phenytoin), the recommended oral dose of exemestane is 50 mg once daily, after a meal.

Proprietary Preparations

Argentina: Aromasin;

Australia: Aromasin;

Austria: Aromasin;

Belgium: Aromasin;

Brazil: Aromasin;

Canada: Aromasin;

Chile: Aromasin;

Czech Republic: Aromasin;

Denmark: Aromasin;

Finland: Aromasin;

France: Aromasine;

Germany; Aromasin;

Greece: Aromasin;

Hong Kong; Aromasin;

Hungary: Aromasin;

Indonesia: Aromasin;

Ireland: Aromasin;

Israel: Aromasin;

Italy: Aromasin;

Malaysia: Aromasin;

Netherlands: Aromasin;

Norway: Aromasin;

New Zealand: Aromasin;

Philippines: Aromasin;

Poland: Aromasin;

Portugal: Aromasin;

Russia: Aromasin;

South Africa: Aromasin;

Singapore: Aromasin;

Spain: Aromasil;

Sweden: Aromasin;

Switzerland: Aromasin;

Thailand: Aromasin;

Turkey: Aromasin;

United Kingdom (UK): Aromasin;

United States of America (USA): Aromasin;

Venezuela: Aromasin.

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