exemestane

Exemestane is a medication approved for the treatment of advanced breast cancer in postmenopausal women, and is also used off-label to prevent breast cancer in high-risk premenopausal women.

Exemestane belongs to a drug class known as aromatase inhibitors which work by blocking the activity of aromatase, an enzyme that plays an important role in the biosynthesis of estrogens, the female sex hormones.

Estrogens are steroid hormones that come in three forms, estrone (E1), estradiol (E2), and estriol (E3). Estrogens are essential for normal sexual development and function, and in addition, have many other important functions in the body. On the other hand, the growth of the majority of breast cancers is stimulated and maintained by estrogens. Exemestane helps prevent, halt or slow down the progression of estrogen-dependent breast cancers.

In postmenopausal women, the ovaries stop producing estrogens and the primary source of estrogens are those derived from the male sex hormones (androgens) androstenedione and testosterone produced by the adrenal gland. Aromatase is responsible for the conversion of the two androgens into estrone and estradiol. By inhibiting aromatase, exemestane reduces the availability of estrogens that cancer cells require to grow.

The uses of exemestane include:

FDA-approved:

• Treatment of advanced breast cancer in postmenopausal women whose disease has progressed following tamoxifen therapy
• Adjuvant treatment of estrogen receptor (ER)-positive early breast cancer in postmenopausal patients who have received 2 to 3 years of tamoxifen, to complete a total of 5 consecutive years of adjuvant hormonal therapy

Off-label:

• Adjuvant therapy in combination with ovarian function suppression, for high-risk hormone-positive breast cancer in premenopausal women
• First-line adjuvant treatment for early ER-positive breast cancer in postmenopausal women
• Risk-reduction for invasive breast cancer in postmenopausal women

• Do not use in patients with known hypersensitivity to exemestane or any of its components.
• Do not use exemestane to treat women who are pregnant or who may become pregnant, the drug can cause loss of a pregnancy or fetal harm.
• Exemestane is indicated for breast cancer in postmenopausal women, and if it must be used in premenopausal women:
  • Verify the pregnancy status of women before initiation of therapy and do not administer it to pregnant women.
  • In case pregnancy occurs during treatment, apprise the patient of potential hazards to the fetus and the potential risk of pregnancy loss.
• Exemestane should not be administered concurrently with estrogen-containing agents as they can interfere with the effects of exemestane.
• Assess the levels of 25-hydroxyvitamin D before the start of exemestane therapy, due to the high prevalence of vitamin D deficiency in women with early breast cancer, and administer vitamin D to those who are deficient.
• Exemestane reduces bone mineral density over time. Assess patient’s bone mineral density before starting treatment, monitor the patient for loss of bone mineral density, and treat appropriately.
• Low lymphocyte count (Grade 3 or 4 lymphopenia) was observed with exemestane therapy, although most patients had preexisting lower grade lymphopenia. Some patients improved or recovered while continuing exemestane, however, there was no significant increase in viral infections, and no opportunistic infections.
• Rarely, elevations of AST, ALT, alkaline phosphatase, and gamma glutamyl transferase enzymes were observed, which may be from liver 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.

Common side effects of exemestane include:

• Fatigue
• Hot flashes
• Pain
• Headache
• Insomnia
• Depression
• Joint pain (arthralgia)
• Low count of lymphocyte white blood cells (lymphocytopenia)
• Increase in serum alkaline phosphatase
• Nausea
• High blood pressure (hypertension)
• Chest pain
• Chest pain associated with coronary artery disease (angina pectoris)
• Reduced blood flow to the heart (ischemic heart disease)
• Heart attack (myocardial infarction)
• Swelling (edema)
• Peripheral edema
• Hair loss (alopecia)
• Excessive sweating (hyperhidrosis)
• Skin reactions including:
  • Rash
  • Dermatitis
  • Itching (pruritus)
• Abdominal pain
• Loss of appetite (anorexia)
• Diarrhea
• Constipation
• Indigestion (dyspepsia)
• Vomiting
• Increased appetite
• Weight gain
• Increase in gamma-glutamyl transferase enzyme
• Increase in serum bilirubin
• Increase in serum creatinine
• Urinary tract infection
• Infection
• Fever
• Swelling due to lymph fluid buildup (lymphedema)
• Anxiety
• Confusion
• Dizziness
• Reduced skin sensation (hypoesthesia)
• Tingling and numbness (paresthesia)
• Tumor pain
• Carpal tunnel syndrome
• Visual disturbance
• Back pain
• Limb pain
• Skeletal pain
• Weakness (asthenia)
• Muscle pain (myalgia)
• Muscle cramps
• Osteoarthritis
• Brittle bones (osteoporosis)
• Pathological fracture
• Shortness of breath (dyspnea)
• Flu-like symptoms
• Upper respiratory tract infection
• Cough
• Nasal inflammation (rhinitis)
• Throat inflammation (pharyngitis)
• Sinus inflammation (sinusitis)
• Bronchial inflammation (bronchitis)

Less common side effects of exemestane include:

• Hypersensitivity reaction
• Heart failure
• Blood vessel block from blood clot (thromboembolism)
• Gastric ulcer
• Elevated liver enzymes (transaminases)
• Liver inflammation (hepatitis)
• Liver inflammation due to impaired bile flow (cholestatic hepatitis)
• Overgrowth of the inner uterine membrane (endometrial hyperplasia)
• Endometrial polyps
• Nerve disease (neuropathy)
• Trigger finger (stenosing tenosynovitis)
• Decreased bone mineral density
• Abnormal bone growth (osteochondrosis)
• Hives (urticaria)
• Acute generalized exanthematous pustulosis, a severe skin disorder

Call your doctor immediately if you experience any of the following symptoms or serious side effects while using this drug:

• Serious heart symptoms include fast or pounding heartbeats, fluttering in your chest, shortness of breath, and sudden dizziness;
• Severe headache, confusion, slurred speech, severe weakness, vomiting, loss of coordination, feeling unsteady;
• Severe nervous system reaction with very stiff muscles, high fever, sweating, confusion, fast or uneven heartbeats, tremors, and feeling like you might pass out; or
• Serious eye symptoms include blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.

This is not a complete list of all side effects or adverse reactions that may occur from the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may also report side effects or health problems to the FDA at 1-800-FDA-1088.

Tablet

• 25 mg

Adult:

Postmenopausal ER-Positive Breast Cancer

• 25 mg orally once/day; continue until tumor progression

Breast Cancer Adjuvant Treatment

• Switch to exemestane after 2-3 years of tamoxifen treatment
• 25 mg orally once/day; continue until tumor progression
• Take after meals

Breast Cancer Prevention (Off-label)

• 2013 American Society of Clinical Oncology (ASCO) guidelines suggest exemestane as an alternative to tamoxifen or raloxifene to prevent invasive breast cancer in high-risk women
• 25 mg orally once/day for 5 years

Dosage Modifications

• Coadministration with potent CYP3A4 inducers: 50 mg orally once/day

Dosing Considerations

• High risk of breast cancer is defined as at least 1 breast biopsy showing lobular carcinoma in situ (LCIS) or atypical hyperplasia, 1 or more first-degree relatives with breast cancer, or a 5-year predicted risk of breast cancer greater than 1.66% (based on the modified Gail model)

Pediatric:

• Safety and efficacy not established

Overdose

• In clinical trials, dosages of up to 800 mg single dose in healthy women volunteers, and up to 600 mg daily for 12 weeks in postmenopausal women with breast cancer were well tolerated. In animal studies, convulsions and death occurred at extremely high doses.
• There is no specific antidote for exemestane, overdose is treated with symptomatic and supportive care, including monitoring of vital signs.

Inform your doctor of all medications you are currently taking, who can advise you on any possible drug interactions. Never begin taking, suddenly discontinue, or change the dosage of any medication without your doctor’s recommendation.

• Exemestane has no known severe interactions with other drugs.
• Serious interactions of exemestane include:
  • abametapir
  • apalutamide
  • enzalutamide
  • ethinylestradiol
  • fexinidazole
  • idelalisib
  • ivosidenib
  • tucatinib
  • voxelotor
• Exemestane has moderate interactions with at least 56 different drugs.
• Mild interactions of exemestane include:
  • bazedoxifene/conjugated estrogens
  • conjugated estrogens
  • conjugated estrogens, vaginal
  • hydrocortisone

The drug interactions listed above are not all of the possible interactions or adverse effects. For more information on drug interactions, visit the RxList Drug Interaction Checker.

It is important to always tell your doctor, pharmacist, or health care provider of all prescription and over-the-counter medications you use, as well as the dosage for each, and keep a list of the information. Check with your doctor or health care provider if you have any questions about the medication.

• There are no studies of exemestane use in pregnant women, however, animal reproductive studies show it can cause fetal harm if used during pregnancy.
• Exemestane may impair fertility in both males and females.
• Women of pregnancy potential should be tested for pregnancy 7 days before initiating exemestane, and the drug should be avoided in pregnant women.
• Women of pregnancy potential should practice effective contraception during exemestane therapy and for one month following the final dose.
• It is not known if exemestane is present in breast milk, however, many drugs are excreted in breast milk. Women should not breastfeed while on exemestane therapy and for one month following the final dose, because of the potential for serious adverse reactions in the breastfed infant.

• Take exemestane exactly as prescribed.
• Store safely out of reach of children.
• In case of overdose, seek medical help or contact Poison Control.