Class: Antineoplastic Agents
VA Class: AN900
Molecular Formula: C20H24O2
CAS Number: 107868-30-4
Brands: Aromasin
Introduction
Antineoplastic agent; irreversible, selective steroidal aromatase inhibitor (type I), structurally related to the natural substrate androstenedione.1 2 3 4 5 6
Uses for Exemestane
Breast Cancer
Treatment of advanced breast cancer in postmenopausal women whose disease has progressed following tamoxifen therapy.1
Exemestane Dosage and Administration
Administration
Oral Administration
Administer orally after a meal.1
Dosage
Adults
Breast Cancer
Oral
25 mg once daily; continue until tumor progression is evident.1
Prescribing Limits
Adults
Dosages >25 mg daily not shown to provide substantially greater suppression of plasma estrogens but may increase adverse effects.1 2 3
Special Populations
Hepatic Impairment
Dosage adjustment does not appear to be necessary.1 (See Special Populations under Pharmacokinetics.)
Renal Impairment
Dosage adjustment does not appear to be necessary.1 (See Special Populations under Pharmacokinetics.)
Cautions for Exemestane
Contraindications
Known hypersensitivity to exemestane or any ingredient in the formulation.1
Warnings/Precautions
Warnings
Fetal/Neonatal Morbidity and Mortality
Possible fetal harm; embryotoxic in rats and embryotoxic and abortifacient in rabbits.1 If used during pregnancy, apprise of potential hazard to fetus and potential risk for loss of the pregnancy.1
General Precautions
Premenopausal Women
Not recommended for use in premenopausal women.1 Possible incomplete estrogen suppression and reflex increases in gonadotropin levels (ovarian hyperstimulation syndrome).6
Estrogenic Agents
Do not administer concomitantly with exemestane.1 (See Estrogenic Agents under Interactions.)
Lymphocytopenia
Risk of grade 3 or 4 lymphocytopenia; no substantial increase in viral infections and no opportunistic infections observed in clinical studies.1
Specific Populations
Pregnancy
Category D.1 (See Fetal/Neonatal Morbidity and Mortality under Cautions.)
Lactation
Distributed into milk in rats; not known whether distributed into human milk.1 Caution advised if a nursing woman is inadvertently exposed to the drug.1
Pediatric Use
Not indicated; safety and efficacy not established.1
Geriatric Use
No special precautions.1
Hepatic Impairment
Safety of chronic administration not established.1
Renal Impairment
Safety of chronic administration not established.1
Common Adverse Effects
Hot flushes (flashes), nausea, fatigue, increased sweating, excessive weight gain, pain, mental depression, insomnia, anxiety, dyspnea, dizziness, headache, edema, vomiting, flu-like symptoms, abdominal pain, anorexia, coughing, hypertension, constipation.1
Interactions for Exemestane
Metabolized by CYP3A4.1 Does not inhibit CYP1A2, 2C9, 2D6, 2E1, or 3A4.1
Drugs Affecting Hepatic Microsomal Enzymes
Inhibitors or inducers of CYP3A4; potential pharmacokinetic interaction (possible increased or decreased serum exemestane concentrations).1 However, based on experience with concomitant ketoconazole (potent CYP3A4 inhibitor), clinically important interactions with CYP3A4 inhibitors unlikely.1
Estrogenic Agents
Potential antagonistic pharmacologic effects.1
Exemestane Pharmacokinetics
Absorption
Bioavailability
Rapidly absorbed following oral administration, with peak concentrations in women with breast cancer or healthy women attained within about 1.2 or 2.9 hours, respectively.1
Steady-state plasma concentrations achieved in approximately 7 days.1
Food
High-fat meal increases plasma exemestane concentrations by approximately 40%.1
Distribution
Extent
Extensively distributed into tissues.1
Crosses placenta.
Distributed into milk in animals; not studied in pregnant or nursing women.1
Plasma Protein Binding
90% (mainly α1-acid glycoprotein and albumin).1
Elimination
Metabolism
Extensively metabolized via CYP3A4 and aldoketoreductases; metabolites are inactive or inhibit aromatase with decreased potency compared with parent drug.1 One metabolite, 17-hydroexemestane, may have androgenic activity.1
Elimination Route
Excreted similarly (42%) in both urine and feces; <1% excreted as unchanged drug in urine.1
Half-life
Approximately 24 hours.1
Special Populations
In patients with moderate or severe hepatic or renal impairment, AUC is approximately 3 times higher than in healthy individuals.1
Stability
Storage
Oral
Tablets
25°C (may be exposed to 15–30°C).1
ActionsActions
Acts as a false substrate and is converted by aromatase to reactive alkylating intermediates that bind covalently to the substrate binding site of the enzyme; this irreversible binding to the active site of aromatase results in its inactivation (i.e., “suicide” inhibition).1 2 4 5 6
Selectively inhibits conversion of androgens to estrogens;1 2 4 5 6 resulting reduction in serum and tumor concentrations of estrogen inhibits tumor growth and delays disease progression.1 6
Selectively inhibits synthesis of estrogens; does not affect synthesis of adrenal corticosteroid, aldosterone, or thyroid hormone.1 2 3 6
Dose-dependent decrease in sex hormone binding globulin (SHBG) observed with dosages ≥ 2.5 mg daily.1 2
Slight, dose-independent increases in serum LH and FSH concentrations observed even at low dosages as result of negative feedback on the pituitary gland.1 2 3
At dosages ≤25 mg daily, no clinically important effect on circulating concentrations of testosterone, androstenedione, dehydroepiandrostenedione sulfate, or 17-hydroxyprogesterone observed.1 3
At dosages ≥200 mg daily, testosterone and androstenedione concentrations are increased.1 3 17-Hydroexemestane, a metabolite, exhibits substantial intrinsic androgenic activity, which may become clinically important at high (e.g., 200 mg daily) dosages.1 2 3
Advice to Patients
Importance of adherence to dosing and medical or laboratory appointment schedules.1
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as concomitant illnesses.1
Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed; warn of potential hazard to the fetus in cases of inadvertent exposure of pregnant women to exemestane.1
Importance of informing patients of other important precautionary information.1 (See Cautions.)
Preparations
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Oral | Tablets | 25 mg | Aromasin | Pfizer |
Comparative Pricing
This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 03/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.
Aromasin 25MG Tablets (PFIZER U.S.): 30/$406.97 or 90/$1189.92
Disclaimer
This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.
The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.
AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions May 2004. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.
References
1. Pharmacia & Upjohn Co. Aromasin (exemestane) tablets prescribing information. Kalamazoo, MI; 1999 Oct 20.
2. Johannessen DC, Engan T, Di Salle E et al. Endocrine and clinical effects of exemestane (PNU 155971), a novel steroidal aromatase inhibitor, in postmenopausal breast cancer patients: a phase I study. Clin Cancer Res. 1997; 3:1101-8. [IDIS 389585] [PubMed 9815789]
3. Evans TRJ, Di Salle E, Ornati G et al. Phase I and endocrine study of exemestane (FCE 24304), a new aromatase inhibitor, in postmenopausal women. Cancer Res. 1992; 52:5933-9. [IDIS 304969] [PubMed 1394219]
4. Geisler J, King N, Anker G et al. In vivo inhibition of aromatization by exemestane, a novel irreversible aromatase inhibitor, in postmenopausal breast cancer patients. Clin Cancer Res. 1998; 4:2089-93. [IDIS 410748] [PubMed 9748124]
5. Reddy P. A review of the newer aromatase inhibitors in the management of metastatic breast cancer. J Clin Pharm Ther. 1998; 23:81-90. [IDIS 415373] [PubMed 9786093]
6. Goss PE, Gwyn KMEH. Current perspectives on aromatase inhibitors in breast cancer. J Clin Oncol. 1994; 12:2460-70. [IDIS 338078] [PubMed 7964964]
7. Anker GB, Refsum H, Ueland PM et al. Influence of aromatase inhibitors on plasma total homocysteine in postmenopausal breast cancer patients. Clin Chem. 1999; 45:252-6. [IDIS 424029] [PubMed 9931048]
a. Pharmacia & Upjohn Co. Aromasin (exemestane) tablets prescribing information. Kalamazoo, MI; 2003 Jul.
More Exemestane resources
- Exemestane Side Effects (in more detail)
- Exemestane Dosage
- Exemestane Use in Pregnancy & Breastfeeding
- Drug Images
- Exemestane Drug Interactions
- Exemestane Support Group
- 10 Reviews for Exemestane - Add your own review/rating
- Exemestane MedFacts Consumer Leaflet (Wolters Kluwer)
- Exemestane Professional Patient Advice (Wolters Kluwer)
- exemestane Advanced Consumer (Micromedex) - Includes Dosage Information
- Aromasin Prescribing Information (FDA)
- Aromasin Consumer Overview
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