Exemestane is a steroidal inhibitor of aromatase which effectively blocks estrogen synthesis in postmenopausal women and is used as a therapy of estrogen receptor-positive breast cancer, usually after resection and after the failure of tamoxifen. Exemestane has been associated with a low rate of serum enzyme elevations during therapy and rare instances of clinically apparent liver injury.
Exemestane is a synthetic androgen analog. Exemestane binds irreversibly to and inhibits the enzyme aromatase, thereby blocking the conversion of cholesterol to pregnenolone and the peripheral aromatization of androgenic precursors into estrogens. (NCI04)
Mechanism of Action of Exemestane
Breast cancer cell growth may be estrogen-dependent. Aromatase (exemestane) is the principal enzyme that converts androgens to estrogens both in pre- and postmenopausal women. While the main source of estrogen (primarily estradiol) is the ovary in premenopausal women, the principal source of circulating estrogens in postmenopausal women is from the conversion of adrenal and ovarian androgens (androstenedione and testosterone) to estrogens (estrone and estradiol) by the aromatase enzyme in peripheral tissues. Estrogen deprivation through aromatase inhibition is an effective and selective treatment for some postmenopausal patients with hormone-dependent breast cancer. Exemestane is an irreversible, steroidal aromatase inactivator, structurally related to the natural substrate androstenedione. It acts as a false substrate for the aromatase enzyme, and is processed to an intermediate that binds irreversibly to the active site of the enzyme causing its inactivation, an effect also known as “suicide inhibition”. Exemestane significantly lowers circulating estrogen concentrations in postmenopausal women but has no detectable effect on the adrenal biosynthesis of corticosteroids or aldosterone. This reduction in serum and tumor concentrations of estrogen delays tumor growth and disease progression. Exemestane has no effect on other enzymes involved in the steroidogenic pathway up to a concentration of at least 600 times higher than that inhibiting the aromatase enzyme.
Indications of Exemestane
- For the treatment of advanced breast cancer in postmenopausal women whose disease has progressed following tamoxifen therapy.
- Stage I Breast Carcinoma
- Refractory, advanced Breast cancer
- Breast cancer that is advanced.
- Breast cancer that is early stage and estrogen receptor positive.
- Exemestane is used in postmenopausal women who have already been treated with tamoxifen citrate. Exemestane is also being studied in the treatment of other types of cancer.
Therapeutic Uses of Exemestane
- Antineoplastic (hormonal).
- Exemestane is indicated for the treatment of advanced breast cancer in postmenopausal women whose disease has progressed following tamoxifen therapy.
- Use of exemestane in premenopausal women is not accepted.
Contra-Indications of Exemestane
- Vitamin D Deficiency
- Decreased Calcification or Density of Bone
- pregnancy
- a mother who is producing milk and breastfeeding
Dosage of Exemestane
Strength: 25 mg
Breast Cancer
- 25 mg orally once a day
Side Effects of Exemestane
The most common
- abdominal or stomach pain
- anxiety
- burning, tingling, or prickly sensations
- confusion
- constipation
- decreased sense of touch
- diarrhea
- dizziness
- a general feeling of tiredness or weakness
Common
- Cough or hoarseness
- difficult or labored breathing
- fever or chills
- lower back or side pain
- mental depression
- swelling of the hands, ankles, feet, or lower legs
- tightness in the chest
- Chest pain
- difficult, burning, or painful urination
- frequent urge to urinate
- a headache
- a sore throat
- unexplained broken bones
Rare
- Abdominal or stomach pain
- clay-colored stools
- confusion
- dark urine
- decreased urine output
- diarrhea
- difficulty with speaking
- dilated neck veins
- dizziness
- double vision
- inability to move the arms, legs, or facial muscles
- inability to speak
- irregular breathing
- irregular heartbeat
- itching or rash
- loss of appetite
- nausea
Drug Interactions of Exemestane
Exemestane may interact with following drugs, supplements & may change the efficacy of drugs
- aripiprazole
- bosentan
- carbamazepine
- dabrafenib
- deferasirox
- dexamethasone
- efavirenz
- estrogens
- etravirine
- fosphenytoin
- methadone
- modafinil
- oxcarbazepine
- pentobarbital
- phenytoin
- primidone
- rifabutin
- rifampin
- St. John’s Wort
Pregnancy & Lactation
FDA pregnancy category – X
Pregnancy
Although the effect of exemestane is unclear, there is some evidence suggesting that taking this medication during pregnancy may cause harm to an unborn baby. Exemestane should not be used during pregnancy unless the benefits outweigh the risks. If you become pregnant while taking this medication, contact your doctor immediately.
Lactation
It is not known if exemestane passes into breast milk. If you are a breast-feeding mother and are taking this medication, it may affect your baby. Talk to your doctor about whether you should continue breastfeeding.
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