Brand name: Aromasin
Drug class: Antiestrogens
- Aromatase Inhibitors
VA class: AN900
Molecular formula: C₂₀H₂₄O₂
CAS number: 107868-30-4

Medically reviewed by Drugs.com on May 22, 2023. Written by ASHP.

Introduction

Antineoplastic agent; irreversible, selective steroidal aromatase inhibitor (type I), structurally related to the natural substrate androstenedione.

Uses for Exemestane

Initial, Sequential, or Extended Adjuvant Therapy for Postmenopausal Women with Early-Stage Hormone Receptor-Positive Breast Cancer

Sequential adjuvant therapy in postmenopausal women with early-stage estrogen receptor-positive breast cancer who have received 2–3 years of adjuvant tamoxifen and are switched to exemestane to complete a total of 5 consecutive years of adjuvant hormonal therapy.

Guidelines from ASCO state that postmenopausal women with node-positive hormone-receptor positive breast cancer should be offered extended adjuvant endocrine therapy with one of the following: aromatase inhibitor therapy for up to a total of 10 years; tamoxifen for 10 years; tamoxifen for 5 years, then an aromatase inhibitor for 5 years; or tamoxifen for 2–3 years, then an aromatase inhibitor for 7–8 years. Women with node-negative breast cancer may also be offered extended adjuvant endocrine therapy for up to a total of 10 years, although benefits are likely narrower due to the lower risk for recurrence.

Consider adverse effects, patient preference, and preexisting conditions when selecting an adjuvant regimen; during the course of adjuvant therapy, patients who are intolerant of one treatment may be switched to a different treatment.

Advanced Breast Cancer in Postmenopausal Women

Treatment of advanced breast cancer in postmenopausal women with progressive disease after tamoxifen therapy.

Adjuvant Therapy for Early-Stage Breast Cancer in Premenopausal Women

Use of endocrine therapy (i.e., anastrozole, exemestane, letrozole, tamoxifen) in combination with ovarian suppression^{† [off-label]} as adjuvant therapy in premenopausal women^{† [off-label]} with early-stage hormone receptor-positive breast cancer may be considered a reasonable choice (accepted).

Reduction in the Incidence of Breast Cancer in Women at High Risk

Exemestane has been used for the reduction in the incidence of breast cancer among women who are at high risk of developing the disease^{† [off-label]}.

Exemestane Dosage and Administration

General

Pretreatment Screening

• Assess baseline 25-hydroxyvitamin D levels prior to treatment.

• Assess bone mineral density at baseline in patients with osteoporosis or at risk for osteoporosis.

• Pregnancy testing for females of reproductive potential is recommended within 7 days prior to starting exemestane.

Patient Monitoring

• Monitor patients for bone mineral density loss, particularly those with osteoporosis or at risk for osteoporosis.

Administration

Oral Administration

Exemestane is administered orally once daily after a meal.

Dosage

Adults

Breast Cancer

Sequential Adjuvant Therapy for Postmenopausal Women with Early-stage Hormone Receptor-Positive Breast Cancer

Oral

25 mg once daily. Initiate following completion of 2–3 years of adjuvant tamoxifen therapy to complete a total of 5 consecutive years of adjuvant hormonal therapy.

Advanced Breast Cancer in Postmenopausal Women

Oral

25 mg once daily.

Initial Adjuvant Therapy for Postmenopausal Women with Early-Stage Hormone Receptor-Positive Breast Cancer† [off-label]

Oral

25 mg once daily for up to 10 years^{† [off-label]}.

Extended Adjuvant Therapy for Postmenopausal Women with Early-Stage Hormone Receptor-Positive Breast Cancer†

Oral

25 mg once daily for up to 10 years^†.

Adjuvant Therapy for Early-Stage Breast Cancer in Premenopausal Women in Combination with Ovarian Suppression†

Oral

25 mg once daily for 5 years has been used in combination with ovarian suppression^†.

Reduction in the Incidence of Breast Cancer in Women at High Risk

Oral

25 mg once daily has been used^†.

Dosage Modification for Concomitant Use with Drugs that Induce CYP3A4

Strong CYP3A4 inducers may decrease exemestane exposure. The recommended dosage of exemestane when given concurrently with strong CYP3A4 inducers (e.g., rifampin [rifampicin] or phenytoin) is 50 mg once daily after a meal.

Special Populations

Renal Impairment

Dosage adjustment does not appear to be necessary.

Hepatic Impairment

Dosage adjustment does not appear to be necessary.

Geriatric Patients

The manufacturer makes no recommendations for dosage adjustments based on age.

Cautions for Exemestane

Contraindications

• Known hypersensitivity to exemestane or any ingredient in the formulation.

Warnings/Precautions

Reductions in Bone Mineral Density

Postmenopausal women receiving an aromatase inhibitor as adjuvant therapy are at high risk for osteoporosis.

Greater reductions in bone mineral density (BMD) at lumbar spine and hip observed over 2 years in patients receiving exemestane (3.1 and 4.2%, respectively) versus tamoxifen (0.2 and 0.3%, respectively). Another study showed greater reductions in lumbar spine and hip BMD over 2 years in patients receiving exemestane (3.5 and 4.6%, respectively) versus placebo (2.4 and 2.6%, respectively).

Incidence of fractures higher in patients switched to exemestane after receiving 2–3 years of adjuvant tamoxifen than in those continuing tamoxifen to complete 5 years of adjuvant therapy.

Assess bone density by bone densitometry at the commencement of exemestane treatment in women with osteoporosis or at risk of osteoporosis. Monitor patients for BMD loss and treat as appropriate.

Vitamin D Assessment

Assess vitamin D (25-hydroxyvitamin D) levels prior to beginning therapy with an aromatase inhibitor due to the high prevalence of vitamin D deficiency among women with breast cancer. Supplementation with vitamin D may be necessary.

Administration with Estrogen-containing Agents.

Do not administer estrogen-containing agents concomitantly with exemestane. (See Specific Drugs under Interactions.)

Laboratory Abnormalities

Grade 3 or 4 lymphocytopenia reported in 20% of exemestane-treated patients with advanced breast cancer. Most patients (89%) had preexisting lower-grade lymphocytopenia; 40% recovered or improved during exemestane therapy. No substantial increase in viral infections and no opportunistic infections observed in clinical studies.

In early-stage breast cancer, hematologic abnormalities reported less frequently with exemestane than with tamoxifen treatment; grade 3 or 4 abnormalities reported rarely.

In advanced breast cancer, serum AST, ALT, alkaline phosphatase, and γ-glutamyltransferase (γ-glutamyltranspeptidase, GGT, GGTP) concentrations >5 times the ULN (i.e., grade 3 or worse) reported rarely in patients receiving exemestane; generally attributable to bone or liver metastasis. In patients without evidence of liver metastasis, grade 3–4 GGT elevations reported at similar rates in exemestane- or megestrol-treated patients.

In early-stage breast cancer, elevated bilirubin and alkaline phosphatase concentrations reported more frequently with exemestane than with tamoxifen or placebo treatment. Grade 3–4 bilirubin elevations reported rarely.

Elevated S_cr reported.

Use in Premenopausal Women

Manufacturer states exemestane is not indicated for treatment of breast cancer in premenopausal women. Possible incomplete estrogen suppression and reflex increases in gonadotropin levels (ovarian hyperstimulation syndrome).

Has been used in combination with ovarian suppression as adjuvant therapy in premenopausal women^† with early-stage hormone receptor-positive breast cancer.

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm; embryotoxic, fetotoxic, and abortifacient in animals. Test for pregnancy status within 7 days prior to initiation of the drug. Advise females of reproductive potential to use effective contraceptive methods during therapy and for 1 month after discontinuance of the drug. If used during pregnancy or if patient becomes pregnant, apprise of potential fetal hazard and potential risk for pregnancy loss.

Specific Populations

Pregnancy

May cause fetal harm. No adequate and well-controlled studies in pregnant women. If exemestane is used during pregnancy or if the patient becomes pregnant while receiving the drug, inform the patient of the potential hazard to the fetus and the potential risk for pregnancy loss.

Lactation

Distributed into milk in rats; not known whether distributed into human milk. Effects on nursing infant and milk production also unknown. Discontinue nursing during therapy and for ≥1 month after drug discontinuance.

Females and Males of Reproductive Potential.

Manufacturer recommends testing for pregnancy status within 7 days prior to initiation of exemestane. Advise females of reproductive potential to use an effective method of contraception while taking exemestane and for 1 month after the last dose of treatment.

May impair female and male fertility.

Pediatric Use

Not indicated; safety and efficacy not established.

Geriatric Use

No special precautions.

Hepatic Impairment

Systemic exposure increased in patients with moderate or severe hepatic impairment; however, dosage adjustment does not appear to be necessary.

Renal Impairment

Systemic exposure increased in patients with moderate or severe renal impairment; however, dosage adjustment does not appear to be necessary.

Common Adverse Effects

Adverse events reported in ≥10% of patients with early-stage breast cancer receiving exemestane include hot flushes (flashes), fatigue, arthralgia, headache, insomnia, and increased sweating.

Adverse events reported in ≥5% of patients with advanced breast cancer receiving exemestane include fatigue, nausea, and hot flushes. Most adverse events were mild to moderate in severity.

Drug Interactions

Metabolized by CYP3A4. Does not inhibit CYP1A2, 2C9, 2D6, 2E1, or 3A4.

Drugs Affecting Hepatic Microsomal Enzymes

CYP3A4 inhibitors: Clinically important pharmacokinetic interactions are unlikely.

CYP3A4 inducers: Possible decreased exposure to exemestane. If a potent CYP3A4 inducer is used concomitantly, increase exemestane dosage to 50 mg once daily.

Specific Drugs

Exemestane Pharmacokinetics

Absorption

Bioavailability

Rapidly absorbed following oral administration; peak concentrations in women with breast cancer or healthy women attained within about 1.2 or 2.9 hours, respectively. Approximately 42% of an oral dose is absorbed from the GI tract.

Following repeated doses, mean AUC in women with breast cancer is approximately twice that in healthy women.

Food

High-fat meal increases AUC and peak plasma exemestane concentrations by 59 and 39%, respectively.

Special Populations

Age (43–68 years) and sex do not affect pharmacokinetics.

Distribution

Extent

Extensively distributed into tissues.

Crosses placenta.

Distributed into milk in animals; not studied in pregnant or nursing women.

Plasma Protein Binding

90% (mainly α₁-acid glycoprotein and albumin).

Elimination

Metabolism

Extensively metabolized via CYP3A4 and aldoketoreductases; metabolites are inactive or inhibit aromatase with decreased potency compared with parent drug. One metabolite, 17-hydroexemestane, may have androgenic activity.

Elimination Route

Excreted similarly (42%) in both urine and feces; <1% excreted as unchanged drug in urine.

Half-life

Approximately 24 hours.

Special Populations

In patients with moderate or severe hepatic (Child-Pugh class B or C) or renal (Cl_cr <35 mL/minute per 1.73 m²) impairment, AUC is approximately 3 times higher than in healthy individuals.

Stability

Storage

Oral

Tablets

Store at 25°C (excursions permitted between 15–30°C).

Actions

• 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).

• Selectively inhibits conversion of androgens to estrogens; resulting reduction in serum and tumor concentrations of estrogen inhibits tumor growth and delays disease progression.

• Selectively inhibits synthesis of estrogens; does not affect synthesis of adrenal corticosteroid, aldosterone, or thyroid hormone.

• Dose-dependent decrease in sex hormone binding globulin (SHBG) observed with dosages ≥2.5 mg daily.

• Slight, dose-independent increases in serum LH and FSH concentrations observed even at low dosages as result of negative feedback on the pituitary gland.

• At dosages ≤25 mg daily, no clinically important effect on circulating concentrations of androstenedione, dehydroepiandrostenedione sulfate, or 17-hydroxyprogesterone and only small decreases in circulating concentrations of testosterone observed.

• At dosages ≥200 mg daily, testosterone and androstenedione concentrations are increased. 17-Hydroexemestane, a metabolite, exhibits substantial intrinsic androgenic activity, which may become clinically important at high (e.g., 200 mg daily) dosages.

Advice to Patients

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and herbal supplements, as well as any concomitant illnesses.

• Importance of not taking estrogen-containing agents concomitantly with exemestane.

• Risk of osteoporosis. Monitor bone mineral density (BMD).

• Risk of fetal harm and pregnancy loss. Advise females of reproductive potential to use effective contraception during exemestane therapy and for 1 month after the last dose of the drug.

• Patients also should be advised that exemestane is FDA-labeled for use only in postmenopausal women.

• Advise women to avoid breast-feeding while receiving exemestane and for 1 month following discontinuance of therapy.

• Importance of informing patients of other important precautionary information. (See Cautions.)

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

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Frequently asked questions

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