Drug Formulary information is intended for use by healthcare professionals. It is not intended to be medical advice. Some of the information, including information about funding for cancer drugs, does not apply to all patients. Cancer treatment plans are unique to each patient. If you are a patient, please speak with your healthcare team to understand how this information applies to you.
exemestane
Exemestane is a potent and irreversible steroidal aromatase inactivator. It inhibits the conversion of adrenally generated androstenedione to estrone by aromatase in peripheral tissues, such as adipose tissue as well as in tumours. Exemestane does not affect the synthesis of adrenal corticosteroid, aldosterone, or thyroid hormone.
| Bioavailability |
> 42% |
| Effects with food |
Plasma level is increased (approximately by 40%) with high fat meals. |
| Time to reach steady state |
Within 7 days |
Exemestane is distributed extensively into tissue.
| PPB |
90% (albumin and α1 acid glycoprotein) |
Exemestane is extensively (90%) metabolized in the liver by cytochrome P450 isoenzyme 3A4 and aldoketoreductases.
| Active metabolites |
No |
| Inactive metabolites |
Yes |
Metabolites are excreted equally in the urine and feces.
| Feces |
42% |
| Urine |
42% (< 1% unchanged) |
| Half-life |
24 hours (terminal) |
- Hormonal treatment of advanced breast cancer in women with natural or artificially induced post-menopausal status whose disease has progressed following anti-estrogen therapy.
- Sequential adjuvant treatment of postmenopausal women with estrogen receptor-positive early breast cancer who have received 2-3 years of initial adjuvant tamoxifen therapy.
Other Uses:
- Endometrial cancer
Emetogenic Potential:
The following table contains adverse effects reported in > 5% of postmenopausal patients with early breast cancer in sequential adjuvant clinical trials. It also includes severe, life-threatening, or post-marketing adverse events from other sources.
| ORGAN SITE | SIDE EFFECT* (%) | ONSET** | |||
|---|---|---|---|---|---|
| Cardiovascular | Arterial thromboembolism (rare) | E | |||
| Cardiotoxicity (1%) | D | ||||
| Hypertension (10%) | E | ||||
| Venous thromboembolism (2%) | E | ||||
| Dermatological | Alopecia (15%) | D | |||
| Rash (7%) (may be severe) | E | ||||
| Gastrointestinal | Diarrhea (4%) | E | |||
| GI ulcer (<1%) | E D | ||||
| Nausea (9%) | I E | ||||
| General | Fatigue (16%) | E | |||
| Hematological | Myelosuppression (<1% severe) | E | |||
| Hepatobiliary | Hepatitis (rare) | E | |||
| ↑ LFTs (≤16%) (may be severe) | E | ||||
| Hypersensitivity | Hypersensitivity (rare, has occurred up to 4 weeks after starting treatment; see rash) | I E | |||
| Metabolic / Endocrine | ↑ Cholesterol (4%) | E D | |||
| Musculoskeletal | Fracture (5%) | D | |||
| Musculoskeletal pain (18%) | E | ||||
| Osteoporosis (5%) | E | ||||
| Other (3%) (carpal tunnel syndrome) | E | ||||
| Neoplastic | Secondary malignancy (4%) | D | |||
| Nervous System | Anxiety (4%) | E | |||
| Depression (6%) | E D | ||||
| Dizziness (10%) | E | ||||
| Headache (14%) | E | ||||
| Insomnia (13%) | E | ||||
| Paresthesia (3%) | E | ||||
| Renal | Creatinine increased (6%) | E | |||
| Reproductive and breast disorders | Estrogen deprivation symptoms (≤22%) | E D | |||
| Vaginal bleeding (4%) | E D | ||||
* "Incidence" may refer to an absolute value or the higher value from a reported range.
"Rare"
may refer to events with < 1% incidence, reported in post-marketing, phase 1 studies,
isolated data or anecdotal
reports.
** I = immediate (onset in hours to days)
E = early (days to weeks)
D = delayed (weeks to months)
L = late (months to years)
The most common side effects for exemestane include estrogen deprivation symptoms, musculoskeletal pain, fatigue, ↑ LFTs, alopecia, headache, insomnia, hypertension and dizziness.
Severe rash, usually early, including erythema multiforme and acute generalized exanthematus pustulosis (AGEP) has been reported.
As compared with megestrol acetate in advanced breast cancer, exemestane produced fewer side effects, including less weight gain, but caused more hot flashes, depression, insomnia, dizziness, anorexia, nausea, and vomiting. As compared to tamoxifen in early breast cancer, exemestane had higher incidences of fatigue, headache, hot flashes, musculoskeletal and nervous system disorders, osteoporosis, (± fractures), hypercholesterolemia, cardiovascular events, ↑ LFTs and ↑ creatinine.
Patients treated with aromatase inhibitors may be at a higher risk for cardiovascular events as well as osteoporosis.
Refer to protocol by which patient is being treated.
Assess patient’s risk factors for osteoporosis and consider calcium and vitamin D supplements and bisphosphonates where appropriate. Refer patients to the Bone Health During Cancer Treatment pamphlet for more information.
| Toxicity | Exemestane Dose |
| Myelosuppression | No adjustment required. |
| Severe cutaneous reactions or acute generalized exanthematus pustulosis (AGEP) | Discontinue permanently. |
Although AUC is tripled in the presence of liver impairment (Child-Pugh C), adverse effects are not increased. No dosage adjustment is required.
Although AUC is tripled in the presence of severe renal impairment (CrCl < 30 mL/min), adverse effects are not increased. No dosage adjustment is required.
No dosage adjustment is required.
Safety and efficacy not established.
-
Tablets should be swallowed whole with a glass of water after a meal (to enhance absorption).
-
Store tablets at room temperature (15-30°C).
- Patients with known hypersensitivity to exemestane or any of its components
- Use is not recommended in pre-menopausal women*.
- Patients with pre-existing severe osteoporosis, a history of osteoporotic fracture or significant cardiac disorders were excluded from clinical trials in early breast cancer.
- Exemestane may increase risk of gastric ulcers especially in patients on NSAIDs and/or with a prior history.
*not receiving ovarian suppression
Other Drug Properties:
-
Carcinogenicity:
Probable
-
Fetotoxicity:
Yes
In animal studies, exemestane caused placental enlargement, dystocia, and prolonged gestation.
-
Abortifacient effects:
Yes
Exemestane is not recommended for use in pregnancy. Adequate contraception should be used by both sexes during treatment, and for at least 6 months (general recommendation) after the last dose.
-
Excretion into breast milk:
Yes
Breastfeeding is not recommended during treatment. Exemestane is excreted into breast milk in animal studies.
-
Fertility effects:
Probable
Exemestane is metabolized by cytochrome P450 CYP 3A4 and aldoketoreductases. It does not inhibit any of the major CYP isoenzymes, including CYP1A2, 2C9, 2D6, 2E1, and 3A.
CYP3A4 inhibition (e.g. ketoconazole) showed no significant effect on exemestane pharmacokinetics.
CYP3A4 induction (e.g. rifampin) produced pharmacokinetic effects but did not affect the suppression of plasma estrogen concentrations. No dose adjustment is required.
| AGENT | EFFECT | MECHANISM | MANAGEMENT |
|---|---|---|---|
| Estrogen-containing or estrogenic agents | ↓ effect of exemestane | Antagonistic effects | Avoid concomitant use |
| NSAIDS | May ↑ risk of gastric ulcers | Unknown | Caution; monitor |
| Warfarin | Possible INR level changes when switched from tamoxifen to exemestane | Possible interaction between tamoxifen and warfarin (exemestane not expected to interact with warfarin) | Monitor PT/INR, especially at switch from tamoxifen to exemestane |
| Monitor Type | Monitor Frequency |
|---|---|
Cholesterol and lipids evaluation |
Baseline and as clinically indicated |
Bone mineral density |
Baseline and as clinically indicated |
Clinical assessment of estrogen deprivation symptoms, fatigue, cardiovascular, musculoskeletal, thromboembolism, hypersensitivity, skin and GI effects |
At each visit |
Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version
| Monitor Type | Monitor Frequency |
|---|---|
| CBC | Baseline and as clinically indicated |
| Liver and renal function tests | Baseline and as clinically indicated |
INR for patients on warfarin (when switching from tamoxifen to exemestane) |
As clinically indicated |
Clemett D, Lamb H. Exemestane: a review of its use in postmenopausal women with advanced breast cancer. Drugs 2000 Jun; 59(6): 1279-96.
Prescribing Information: Aromasin® (exemestane). Pfizer Inc (USA). May 2018.
Product Monograph: Aromasin® (exemestane). Pfizer Canada Inc. March 6, 2018.
November 2020 Updated mechanism of action/pharmacokinetics, indications, special precautions and interactions sections
Refer to the New Drug Funding Program or Ontario Public Drug Programs websites for the most up-to-date public funding information.
The information set out in the drug monographs, regimen monographs, appendices and symptom management information (for health professionals) contained in the Drug Formulary (the "Formulary") is intended for healthcare providers and is to be used for informational purposes only. The information is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects of a particular drug, nor should it be construed to indicate that use of a particular drug is safe, appropriate or effective for a given condition. The information in the Formulary is not intended to constitute or be a substitute for medical advice and should not be relied upon in any such regard. All uses of the Formulary are subject to clinical judgment and actual prescribing patterns may not follow the information provided in the Formulary.
The format and content of the drug monographs, regimen monographs, appendices and symptom management information contained in the Formulary will change as they are reviewed and revised on a periodic basis. The date of last revision will be visible on each page of the monograph and regimen. Since standards of usage are constantly evolving, it is advised that the Formulary not be used as the sole source of information. It is strongly recommended that original references or product monograph be consulted prior to using a chemotherapy regimen for the first time.
Some Formulary documents, such as the medication information sheets, regimen information sheets and symptom management information (for patients), are intended for patients. Patients should always consult with their healthcare provider if they have questions regarding any information set out in the Formulary documents.
While care has been taken in the preparation of the information contained in the Formulary, such information is provided on an “as-is” basis, without any representation, warranty, or condition, whether express, or implied, statutory or otherwise, as to the information’s quality, accuracy, currency, completeness, or reliability.
CCO and the Formulary’s content providers shall have no liability, whether direct, indirect, consequential, contingent, special, or incidental, related to or arising from the information in the Formulary or its use thereof, whether based on breach of contract or tort (including negligence), and even if advised of the possibility thereof. Anyone using the information in the Formulary does so at his or her own risk, and by using such information, agrees to indemnify CCO and its content providers from any and all liability, loss, damages, costs and expenses (including legal fees and expenses) arising from such person’s use of the information in the Formulary.