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Exemestane

Medically reviewed by Drugs.com. Last updated on Jul 10, 2020.

Pronunciation

(ex e MES tane)

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Aromasin: 25 mg

Generic: 25 mg

Brand Names: U.S.

  • Aromasin

Pharmacologic Category

  • Antineoplastic Agent, Aromatase Inhibitor

Pharmacology

Exemestane is an irreversible, steroidal aromatase inactivator. It is structurally related to androstenedione, and is converted to an intermediate that irreversibly blocks the active site of the aromatase enzyme, leading to inactivation ("suicide inhibition") and thus preventing conversion of androgens to estrogens in peripheral tissues. Significantly lowers circulating estrogens in postmenopausal breast cancers where growth is estrogen-dependent.

Absorption

Rapid and moderate (~42%) following oral administration; AUC and Cmax increased by 59% and 39%, respectively, following a high-fat breakfast (compared to fasted state)

Distribution

Extensive into tissues

Metabolism

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

Excretion

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

Time to Peak

Women with breast cancer: 1.2 hours

Half-Life Elimination

~24 hours

Protein Binding

90%, primarily to albumin and α1-acid glycoprotein

Special Populations: Renal Function Impairment

AUC is approximately 3 times higher in those with moderate or severe renal insufficiency compared to patients with normal renal function.

Special Populations: Hepatic Function Impairment

AUC increased approximately 3 times in those with moderate or severe hepatic insufficiency compared to patients with normal hepatic function.

Use: Labeled Indications

Breast cancer: Treatment of advanced breast cancer in postmenopausal women whose disease has progressed following tamoxifen therapy; adjuvant treatment of postmenopausal women with estrogen receptor-positive early breast cancer following 2 to 3 years of tamoxifen (for a total of 5 consecutive years of adjuvant therapy).

Off Label Uses

First-line adjuvant treatment of estrogen receptor-positive early breast cancer in postmenopausal women

Data from a phase III, multicenter, multinational, randomized, open-label trial supports the use of exemestane in the treatment of this condition [van de Veld 2011].

Based on the American Society of Clinical Oncology Clinical Practice Guidelines for Adjuvant Endocrine Therapy for Women with Hormone Receptor-Positive Breast Cancer, exemestane is effective and recommended as adjuvant treatment for early breast cancer.

Risk reduction for invasive breast cancer in postmenopausal women

Data from a randomized, placebo-controlled, double-blind trial supports the use of exemestane in this setting [Goss 2011].

Based on the American Society of Clinical Oncology Clinical Practice Guidelines on the Use of Pharmacologic Interventions for Breast Cancer Risk, exemestane (as an alternative to tamoxifen and/or raloxifene) is effective and recommended to reduce the risk of invasive breast cancer (ie, ER-positive breast cancer) in post-menopausal women.

Contraindications

Known hypersensitivity to exemestane or any component of the formulation

Dosing: Adult

Breast cancer, advanced: Postmenopausal females: Oral: 25 mg once daily; continue until tumor progression

Breast cancer, early (adjuvant treatment): Postmenopausal females: Oral: 25 mg once daily (following 2 to 3 years of tamoxifen therapy) for a total duration of 5 years of endocrine therapy (in the absence of recurrence or contralateral breast cancer).

Duration of therapy: American Society of Clinical Oncology (ASCO) guidelines for Adjuvant Endocrine Therapy of Hormone Receptor-Positive Breast Cancer (Focused Update) recommend a maximum duration of 5 years of aromatase inhibitor (AI) therapy for postmenopausal women; AIs may be combined with tamoxifen for a total duration of up to 10 years of endocrine therapy. Refer to the guidelines for specific recommendations based on menopausal status and tolerability (Burstein 2014). In a phase III study with another AI (letrozole), treatment with an additional 5 years of AI therapy (for a total of 10 years of aromatase inhibitor therapy) demonstrated a significantly improved rate of disease-free survival and a decreased risk of disease recurrence and contralateral breast cancer (when compared to placebo), although overall survival was not significantly different between groups and bone-related adverse events occurred more frequently with letrozole versus placebo (Goss 2016).

Breast cancer, early (first-line adjuvant treatment; off-label use): Postmenopausal females: Oral: 25 mg once daily for 5 years (Burstein 2010; van de Velde 2011).

Duration of therapy: ASCO guidelines for Adjuvant Endocrine Therapy of Hormone Receptor-Positive Breast Cancer (Focused Update) recommend a maximum duration of 5 years of aromatase inhibitor (AI) therapy for postmenopausal women; AIs may be combined with tamoxifen for a total duration of up to 10 years of endocrine therapy. Refer to the guidelines for specific recommendations based on menopausal status and tolerability (Burstein 2014). In a phase III study with another AI (letrozole), treatment with an additional 5 years of AI therapy (for a total of 10 years of aromatase inhibitor therapy) demonstrated a significantly improved rate of disease-free survival and a decreased risk of disease recurrence and contralateral breast cancer (when compared to placebo), although overall survival was not significantly different between groups and bone-related adverse events occurred more frequently with letrozole versus placebo (Goss 2016).

Breast cancer, risk reduction (off-label use): Postmenopausal females ≥35 years: Oral: 25 mg once daily for 5 years (Goss 2011; Visvanathan 2013)

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

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Geriatric

Refer to adult dosing.

Administration

Administer after a meal.

Dietary Considerations

Patients on aromatase inhibitor therapy should receive vitamin D and calcium supplements.

Storage

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

Drug Interactions

CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

CYP3A4 Inducers (Strong): May decrease the serum concentration of Exemestane. Management: Increase the exemestane dose to 50 mg/day in patients receiving concurrent strong CYP3A4 inducers. Monitor patients closely for evidence of toxicity or inadequate clinical response. Consider therapy modification

Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Enzalutamide: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring. Consider therapy modification

Erdafitinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Estrogen Derivatives: May diminish the therapeutic effect of Exemestane. Avoid combination

Ivosidenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Levomethadone: Aromatase Inhibitors may increase the serum concentration of Levomethadone. Monitor therapy

Methadone: Aromatase Inhibitors may increase the serum concentration of Methadone. Monitor therapy

Mitotane: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane. Consider therapy modification

Sarilumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Siltuximab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

St John's Wort: May decrease the serum concentration of Exemestane. Management: Increase the exemestane dose to 50 mg/day in patients receiving St Johns Wort. Monitor patients closely for evidence of toxicity or inadequate clinical response. Consider therapy modification

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Adverse Reactions

Frequency not always defined. *Incidence not specifically defined, but reported in the range of 1% to 10%.

Cardiovascular: Hypertension (5% to 15%), edema (6% to 7%), ischemic heart disease (2%; angina pectoris, myocardial infarction), chest pain*

Central nervous system: Fatigue (8% to 22%), insomnia (11% to 14%), pain (13%), headache (7% to 13%), depression (6% to 13%), dizziness (8% to 10%), anxiety (4% to 10%), paresthesia (3%), carpal tunnel syndrome (2%), confusion,* hypoesthesia*

Dermatological: Hyperhidrosis (4% to 18%), alopecia (15%), dermatitis (8%), pruritus,* skin rash*

Endocrine & metabolic: Hot flash (13% to 33%), weight gain (8%), increased follicle-stimulating hormone, increased luteinizing hormone, increased sex hormone binding globulin (with daily doses of ≥2.5 mg; dose-dependent)

Gastrointestinal: Nausea (9% to 18%), abdominal pain (6% to 11%), diarrhea (4% to 10%), vomiting (7%), anorexia (6%), constipation (5%), increased appetite (3%), dyspepsia*

Genitourinary: Urinary tract infection (2% to 5%)

Hematologic & oncologic: Lymphedema*

Hepatic: Increased serum alkaline phosphatase (14% to 15%), increased serum bilirubin (5% to 7%)

Infection: Infection*

Neuromuscular & skeletal: Arthralgia (15% to 29%), back pain (9%), limb pain (9%), myalgia (6%), osteoarthritis (6%), weakness (6%), osteoporosis (5%), pathological fracture (4%), muscle cramps (2%)

Ophthalmic: Visual disturbance (5%)

Renal: Increased serum creatinine (6%)

Respiratory: Dyspnea (10%), cough (6%), flu-like symptoms (6%), bronchitis,* pharyngitis,* rhinitis,* sinusitis,* upper respiratory tract infection*

Miscellaneous: Fever (5%)

<1%, postmarketing, and/or case reports: Abnormal bone growth (osteochondrosis), acute generalized exanthematous pustulosis, cardiac failure, cholestatic hepatitis, endometrial hyperplasia, endometrial polyps, gastric ulcer, hepatitis, hypersensitivity reaction, increased gamma-glutamyl transferase, increased serum transaminases, neuropathy, tenosynovitis (fingers), thromboembolism, urticaria

Warnings/Precautions

Concerns related to adverse effects:

• Decreased bone mineral density: Due to decreased circulating estrogen levels, exemestane is associated with a reduction in bone mineral density over time. Decreases (from baseline) in lumbar spine and femoral neck density have been observed (when compared to tamoxifen or placebo in studies where concomitant use of bisphosphonates, calcium and vitamin D were not allowed). Assess bone mineral density at baseline in patients with, or at risk for osteoporosis; monitor during exemestane therapy and initiate osteoporosis treatment if indicated.

• Lymphopenia: Grade 3 or 4 lymphopenia has been observed with exemestane, although most patients had preexisting lower grade lymphopenia; some patients improved or recovered while continuing exemestane. Lymphopenia did not result in a significant increase in viral infections, and no opportunistic infections were observed.

• Lab parameters: Elevations of AST, ALT, alkaline phosphatase, and gamma glutamyl transferase >5 times ULN have been observed (rarely) in patients with advanced breast cancer; may be attributable to underlying liver and/or bone metastases. In patients with early breast cancer, elevations of bilirubin, alkaline phosphatase, and serum creatinine were more common with exemestane treatment than with tamoxifen or placebo.

Concurrent drug therapy issues:

• Estrogen-containing drugs: Exemestane should not be administered concurrently with estrogen-containing drugs.

Other warnings/precautions:

• Appropriate use: Exemestane is not indicated for use in premenopausal women.

• Vitamin D deficiency: Due to high prevalence of vitamin D deficiency in women with breast cancer, assess 25-hydroxy vitamin D levels at baseline and supplement accordingly.

Monitoring Parameters

25-hydroxy vitamin D levels (at baseline); bone mineral density

Reproductive Considerations

Evaluate pregnancy status prior to use. Pregnancy testing is recommended for females of reproductive potential within 7 days prior to therapy initiation. Women of reproductive potential should use effective contraception during treatment and for 1 month after the final dose.

Pregnancy Considerations

Exemestane is not indicated for use in premenopausal women. Based on the mechanism of action and on animal data, exemestane is expected to cause fetal harm if administered to a pregnant woman.

Patient Education

What is this drug used for?

• It is used to treat breast cancer in women after change of life.

• It may be given to you for other reasons. Talk with the doctor.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Hot flashes

• Abdominal pain

• Nausea

• Vomiting

• Constipation

• Increased hunger

• Muscle pain

• Joint pain

• Hair loss

• Loss of strength and energy

• Trouble sleeping

• Sweating a lot

• Back pain

• Diarrhea

• Anxiety

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Swelling

• Chest pain

• Bone pain

• Vision changes

• Depression

• Severe headache

• Severe dizziness

• Passing out

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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