Exemestane – Uses, Dosage, Side Effects, Interactions
Dr. Harun Ar Rashid, MD - Arthritis, Bones, Joints Pain, Trauma, and Internal Medicine Specialist Deal Score0
Exemestane is a steroidal inhibitor of aromatase that effectively blocks estrogen synthesis in postmenopausal women and is used as therapy for 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 an oral steroidal aromatase inhibitor used in the adjuvant treatment of hormonally-responsive (also called hormone-receptor-positive, estrogen-responsive) breast cancer in postmenopausal women. It irreversibly binds to the active site of the enzyme resulting in permanent inhibition.
Exemestane is an irreversible steroidal aromatase inhibitor, with antiestrogen and antineoplastic activities. Upon oral administration, exemestane binds irreversibly to and inhibits the enzyme aromatase, thereby blocking the peripheral aromatization of androgens, including androstenedione and testosterone, to estrogens. This lowers estrogen levels in blood circulation.
Exemestane is a 17-oxo steroid that is androstane-1,4-diene-3,17-dione in which the hydrogens at position 6 are replaced by a double bond to a methylene group. A selective inhibitor of the aromatase (estrogen synthase) system, it is used in the treatment of advanced breast cancer. It has a role as an EC 1.14.14.14 (aromatase) inhibitor, an antineoplastic agent, an environmental contaminant, and a xenobiotic. It is a 17-oxo steroid and a 3-oxo-Delta(1),Delta(4)-steroid. It derives from a hydride of an androstane.
Mechanism of Action
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 irreversibly binds to the active site causing permanent inhibition and necessitating de novo synthesis to restore enzymatic function. 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 at least 600 times higher than that inhibiting the aromatase enzyme.
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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. Exemestane has no effect on other enzymes involved in the steroidogenic pathway up to a concentration at least 600 times higher than that inhibiting the aromatase enzyme.
Indications
- For the treatment of advanced breast cancer in postmenopausal women whose disease has progressed following tamoxifen therapy.
- Exemestane is a steroidal inhibitor of aromatase that effectively blocks estrogen synthesis in postmenopausal women and is used as therapy for 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 an aromatase inhibitor used to treat breast cancer in postmenopausal women after treatment with tamoxifen.
- 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
- Adjuvant treatment of postmenopausal women with estrogen-receptor-positive early breast cancer who have received two to three years of tamoxifen and are switched to exemestane for completion of a total of five consecutive years of adjuvant hormonal therapy.
- Treatment of advanced breast cancer in postmenopausal women whose disease has progressed following tamoxifen therapy.
- Early Breast Cancer
- Refractory, advanced Breast cancer
Use in Cancer
Exemestane is approved to treat:
- Breast cancer is advanced.
- Breast cancer 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.
Contraindications
The following conditions are contraindicated with this drug. Check with your physician if you have any of the following:
- This drug is not indicated for the treatment of breast cancer in premenopausal women.
- low vitamin D levels
- decreased calcification or density of bone
- pregnancy
- a patient who is producing milk and breastfeeding
Dosage
Strengths: 25 mg
Breast Cancer
- 25 mg orally once a day
Side Effects
The Most Common
- hot flushes
- sweating
- muscle or joint pain
- tiredness
- headache
- dizziness
- feeling worried or anxious
- depression
- difficulty falling asleep or staying asleep
- nausea
- vomiting
- increased appetite
- diarrhea
- hair loss
- red, itchy skin
- changes in vision
- swelling of the arms, hands, feet, ankles, or lower legs
- shortness of breath
- chest pain
More Common
- abdominal or stomach pain
- burning, tingling, or prickly sensations
- constipation
- diarrhea
- dizziness
- a general feeling of tiredness or weakness
- headache
- heartburn
- hot flashes
- increased appetite
- increased sweating
- itching
- joint pain
- loss of hair
- muscle pain or cramps
- nausea
- rash
- trouble sleeping
- weight gain
- bone pain
- flu-like symptoms (e.g., cough, hoarseness, sore throat, fever, or chills)
- increased blood pressure (e.g., shortness of breath, fatigue, dizziness, fainting, bluish color to lips, chest pain or pressure)
- increased cholesterol
Rare
- signs of carpal tunnel syndrome (pain or burning in the hands or wrists)
- signs of depression (e.g., poor concentration, changes in weight, changes in sleep, decreased interest in activities, thoughts of suicide)
- signs of a urinary tract infection (e.g., difficult or painful urination, blood in the urine, frequent urge to urinate, lower back or side pain)
- swelling of hands, ankles, feet, or lower legs
- symptoms of liver damage (e.g., yellow skin or eyes, dark urine, clay-colored stools, loss of appetite, nausea, and vomiting, or itching)
- symptoms of a stomach ulcer (e.g., heartburn, burning stomach pain, nausea, vomiting)
- unexplained broken bones
- vaginal bleeding
- signs of a heart attack (e.g., chest pain or pressure, pain extending through shoulder and arm, nausea and vomiting, sweating)
- signs of a blood clot in blood vessels, such as sudden vision change or dizziness, chest pain, pain and swelling in one leg muscle
- sudden development of breathing problems (e.g., shortness of breath, trouble breathing, wheezing, tightness in the chest, or fast or irregular breathing)
- signs of a severe allergic reaction (e.g., hives; difficulty breathing; swelling of the face, lips, tongue, or throat)
- signs of bleeding in the stomach or intestines (e.g., dark and tarry stools, blood coming from rectum, vomiting blood or material that looks like coffee grounds, fast heartbeat, weakness or fainting)
Drug Interactions
| DRUG | INTERACTION |
|---|---|
| Abametapir | The serum concentration of Exemestane can be increased when it is combined with Abametapir. |
| Amiodarone | The metabolism of Exemestane can be decreased when combined with Amiodarone. |
| Amprenavir | The metabolism of Exemestane can be decreased when combined with Amprenavir. |
| Apalutamide | The metabolism of Exemestane can be increased when combined with Apalutamide. |
| Aprepitant | The metabolism of Exemestane can be decreased when combined with Aprepitant. |
| Articaine | The risk or severity of methemoglobinemia can be increased when Exemestane is combined with Articaine. |
| Atazanavir | The metabolism of Exemestane can be decreased when combined with Atazanavir. |
| Avanafil | The serum concentration of Avanafil can be increased when it is combined with Exemestane. |
| Benzocaine | The risk or severity of methemoglobinemia can be increased when Exemestane is combined with Benzocaine. |
| Benzyl alcohol | The risk or severity of methemoglobinemia can be increased when Exemestane is combined with Benzyl alcohol. |
| Berotralstat | The metabolism of Exemestane can be decreased when combined with Berotralstat. |
| Boceprevir | The metabolism of Exemestane can be decreased when combined with Boceprevir. |
| Bupivacaine | The risk or severity of methemoglobinemia can be increased when Exemestane is combined with Bupivacaine. |
| Butacaine | The risk or severity of methemoglobinemia can be increased when Exemestane is combined with Butacaine. |
| Butamben | The risk or severity of methemoglobinemia can be increased when Exemestane is combined with Butamben. |
| Capsaicin | The risk or severity of methemoglobinemia can be increased when Exemestane is combined with Capsaicin. |
| Carbamazepine | The metabolism of Exemestane can be increased when combined with Carbamazepine. |
| Cenobamate | The serum concentration of Exemestane can be decreased when it is combined with Cenobamate. |
| Chloroprocaine | The risk or severity of methemoglobinemia can be increased when Exemestane is combined with Chloroprocaine. |
| Cinchocaine | The risk or severity of methemoglobinemia can be increased when Exemestane is combined with Cinchocaine. |
| Ciprofloxacin | The metabolism of Exemestane can be decreased when combined with Ciprofloxacin. |
| Clarithromycin | The metabolism of Exemestane can be decreased when combined with Clarithromycin. |
| Clozapine | The metabolism of Exemestane can be decreased when combined with Clozapine. |
| Cobicistat | The metabolism of Exemestane can be decreased when combined with Cobicistat. |
| Cocaine | The risk or severity of methemoglobinemia can be increased when Exemestane is combined with Cocaine. |
| Conivaptan | The metabolism of Exemestane can be decreased when combined with Conivaptan. |
| Conjugated estrogens | The therapeutic efficacy of Exemestane can be decreased when used in combination with Conjugated estrogens. |
| Crizotinib | The metabolism of Exemestane can be decreased when combined with Crizotinib. |
| Curcumin | The metabolism of Exemestane can be decreased when combined with Curcumin. |
| Cyclosporine | The metabolism of Exemestane can be decreased when combined with Cyclosporine. |
| Dabrafenib | The serum concentration of Exemestane can be decreased when it is combined with Dabrafenib. |
| Danazol | The metabolism of Exemestane can be decreased when combined with Danazol. |
| Darbepoetin alfa | The risk or severity of Thrombosis can be increased when Darbepoetin alfa is combined with Exemestane. |
| Darunavir | The metabolism of Exemestane can be decreased when combined with Darunavir. |
| Delavirdine | The metabolism of Exemestane can be decreased when combined with Delavirdine. |
| Desvenlafaxine | The metabolism of Exemestane can be decreased when combined with Desvenlafaxine. |
| Dexamethasone | The metabolism of Exemestane can be increased when combined with Dexamethasone. |
| Dienestrol | The therapeutic efficacy of Exemestane can be decreased when used in combination with Dienestrol. |
| Diethylstilbestrol | The therapeutic efficacy of Exemestane can be decreased when used in combination with Diethylstilbestrol. |
| Diltiazem | The metabolism of Exemestane can be decreased when combined with Diltiazem. |
| Diphenhydramine | The risk or severity of methemoglobinemia can be increased when Exemestane is combined with Diphenhydramine. |
| Dronedarone | The metabolism of Exemestane can be decreased when combined with Dronedarone. |
| Dyclonine | The risk or severity of methemoglobinemia can be increased when Exemestane is combined with Dyclonine. |
| Efavirenz | The metabolism of Exemestane can be decreased when combined with Efavirenz. |
| Elvitegravir | The metabolism of Exemestane can be decreased when combined with Elvitegravir. |
| Enzalutamide | The metabolism of Exemestane can be increased when combined with Enzalutamide. |
| Ergotamine | The metabolism of Exemestane can be decreased when combined with Ergotamine. |
| Erythromycin | The metabolism of Exemestane can be decreased when combined with Erythromycin. |
| Erythropoietin | The risk or severity of Thrombosis can be increased when Erythropoietin is combined with Exemestane. |
| Esterified estrogens | The therapeutic efficacy of Exemestane can be decreased when used in combination with Esterified estrogens. |
| Estetrol | The therapeutic efficacy of Exemestane can be decreased when used in combination with Estetrol. |
| Estradiol | The therapeutic efficacy of Exemestane can be decreased when used in combination with Estradiol. |
| Estradiol acetate | The therapeutic efficacy of Exemestane can be decreased when used in combination with Estradiol acetate. |
| Estradiol benzoate | The therapeutic efficacy of Exemestane can be decreased when used in combination with Estradiol benzoate. |
| Estradiol cypionate | The therapeutic efficacy of Exemestane can be decreased when used in combination with Estradiol cypionate. |
| Estradiol valerate | The therapeutic efficacy of Exemestane can be decreased when used in combination with Estradiol valerate. |
| Estriol | The therapeutic efficacy of Exemestane can be decreased when used in combination with Estriol. |
| Estrone | The therapeutic efficacy of Exemestane can be decreased when used in combination with Estrone. |
| Estrone sulfate | The therapeutic efficacy of Exemestane can be decreased when used in combination with Estrone sulfate. |
| Ethinylestradiol | The therapeutic efficacy of Exemestane can be decreased when used in combination with Ethinylestradiol. |
| Ethyl chloride | The risk or severity of methemoglobinemia can be increased when Exemestane is combined with Ethyl chloride. |
| Etidocaine | The risk or severity of methemoglobinemia can be increased when Exemestane is combined with Etidocaine. |
| Fluconazole | The metabolism of Exemestane can be decreased when combined with Fluconazole. |
| Fluvoxamine | The metabolism of Exemestane can be decreased when combined with Fluvoxamine. |
| Fosnetupitant | The metabolism of Exemestane can be decreased when combined with Fosnetupitant. |
| Fosphenytoin | The metabolism of Exemestane can be increased when combined with Fosphenytoin. |
| Fusidic acid | The metabolism of Exemestane can be decreased when combined with Fusidic acid. |
| Haloperidol | The serum concentration of Haloperidol can be increased when it is combined with Exemestane. |
| Indinavir | The metabolism of Exemestane can be decreased when combined with Indinavir. |
| Isavuconazole | The metabolism of Exemestane can be decreased when combined with Isavuconazole. |
| Isavuconazonium | The metabolism of Exemestane can be decreased when combined with Isavuconazonium. |
| Isoniazid | The metabolism of Exemestane can be decreased when combined with Isoniazid. |
| Isradipine | The metabolism of Exemestane can be decreased when combined with Isradipine. |
| Itraconazole | The metabolism of Exemestane can be decreased when combined with Itraconazole. |
| Ivosidenib | The metabolism of Exemestane can be increased when combined with Ivosidenib. |
| Ketoconazole | The metabolism of Exemestane can be decreased when combined with Ketoconazole. |
| Levobupivacaine | The risk or severity of methemoglobinemia can be increased when Exemestane is combined with Levobupivacaine. |
| Levoketoconazole | The metabolism of Exemestane can be decreased when combined with Levoketoconazole. |
| Lidocaine | The risk or severity of methemoglobinemia can be increased when Exemestane is combined with Lidocaine. |
| Linagliptin | The metabolism of Exemestane can be decreased when combined with Linagliptin. |
| Lonafarnib | The metabolism of Exemestane can be decreased when combined with Lonafarnib. |
| Lopinavir | The metabolism of Exemestane can be decreased when combined with Lopinavir. |
| Lovastatin | The metabolism of Exemestane can be decreased when combined with Lovastatin. |
| Lumacaftor | The metabolism of Exemestane can be increased when combined with Lumacaftor. |
| Mavacamten | The serum concentration of Exemestane can be decreased when it is combined with Mavacamten. |
| Meloxicam | The risk or severity of methemoglobinemia can be increased when Exemestane is combined with Meloxicam. |
| Mepivacaine | The risk or severity of methemoglobinemia can be increased when Exemestane is combined with Mepivacaine. |
| Mestranol | The therapeutic efficacy of Exemestane can be decreased when used in combination with Mestranol. |
| Methadone | The serum concentration of Methadone can be increased when it is combined with Exemestane. |
| Methimazole | The metabolism of Exemestane can be decreased when combined with Methimazole. |
| Methoxy polyethylene glycol-epoetin beta | The risk or severity of Thrombosis can be increased when Methoxy polyethylene glycol-epoetin beta is combined with Exemestane. |
| Metreleptin | The metabolism of Exemestane can be increased when combined with Metreleptin. |
| Miconazole | The metabolism of Exemestane can be decreased when combined with Miconazole. |
| Midostaurin | The metabolism of Exemestane can be increased when combined with Midostaurin. |
| Milnacipran | The metabolism of Exemestane can be decreased when combined with Milnacipran. |
| Mitotane | The metabolism of Exemestane can be increased when combined with Mitotane. |
| Naloxone | The metabolism of Exemestane can be decreased when combined with Naloxone. |
| Nefazodone | The metabolism of Exemestane can be decreased when combined with Nefazodone. |
| Nelfinavir | The metabolism of Exemestane can be decreased when combined with Nelfinavir. |
| Netupitant | The metabolism of Exemestane can be decreased when combined with Netupitant. |
| Nicardipine | The metabolism of Exemestane can be decreased when combined with Nicardipine. |
| Nilotinib | The metabolism of Exemestane can be decreased when combined with Nilotinib. |
| Nilvadipine | The metabolism of Exemestane can be decreased when combined with Nilvadipine. |
| Oxetacaine | The risk or severity of methemoglobinemia can be increased when Exemestane is combined with Oxetacaine. |
| Oxybuprocaine | The risk or severity of methemoglobinemia can be increased when Exemestane is combined with Oxybuprocaine. |
| Peginesatide | The risk or severity of Thrombosis can be increased when Peginesatide is combined with Exemestane. |
| Pentobarbital | The metabolism of Exemestane can be increased when combined with Pentobarbital. |
| Phenobarbital | The metabolism of Exemestane can be increased when combined with Phenobarbital. |
| Phenol | The risk or severity of methemoglobinemia can be increased when Exemestane is combined with Phenol. |
| Phenytoin | The metabolism of Exemestane can be increased when combined with Phenytoin. |
| Pitolisant | The serum concentration of Exemestane can be decreased when it is combined with Pitolisant. |
| Polyestradiol phosphate | The therapeutic efficacy of Exemestane can be decreased when used in combination with Polyestradiol phosphate. |
| Posaconazole | The metabolism of Exemestane can be decreased when combined with Posaconazole. |
| Pramocaine | The risk or severity of methemoglobinemia can be increased when Exemestane is combined with Pramocaine. |
| Prilocaine | The risk or severity of methemoglobinemia can be increased when Exemestane is combined with Prilocaine. |
| Primaquine | The metabolism of Exemestane can be decreased when combined with Primaquine. |
| Primidone | The metabolism of Exemestane can be increased when combined with Primidone. |
| Procaine | The risk or severity of methemoglobinemia can be increased when Exemestane is combined with Procaine. |
| Proparacaine | The risk or severity of methemoglobinemia can be increased when Exemestane is combined with Proparacaine. |
| Propoxycaine | The risk or severity of methemoglobinemia can be increased when Exemestane is combined with Propoxycaine. |
| Quinestrol | The therapeutic efficacy of Exemestane can be decreased when used in combination with Quinestrol. |
| Ribociclib | The metabolism of Exemestane can be decreased when combined with Ribociclib. |
| Rifampicin | The metabolism of Exemestane can be increased when combined with Rifampicin. |
| Rifamycin | The metabolism of Exemestane can be increased when combined with Rifamycin. |
| Rifapentine | The metabolism of Exemestane can be increased when combined with Rifapentine. |
| Ritonavir | The serum concentration of Exemestane can be increased when it is combined with Ritonavir. |
| Ropivacaine | The risk or severity of methemoglobinemia can be increased when Exemestane is combined with Ropivacaine. |
| Saquinavir | The metabolism of Exemestane can be decreased when combined with Saquinavir. |
| Satralizumab | The serum concentration of Exemestane can be decreased when it is combined with Satralizumab. |
| Simeprevir | The metabolism of Exemestane can be decreased when combined with Simeprevir. |
| Somatrogon | The metabolism of Exemestane can be increased when combined with Somatrogon. |
| Sotorasib | The serum concentration of Exemestane can be decreased when it is combined with Sotorasib. |
| St. John’s Wort | The metabolism of Exemestane can be increased when combined with St. John’s Wort. |
| Stiripentol | The metabolism of Exemestane can be decreased when combined with Stiripentol. |
| Synthetic Conjugated Estrogens, A | The therapeutic efficacy of Exemestane can be decreased when used in combination with Synthetic Conjugated Estrogens, A. |
| Synthetic Conjugated Estrogens, B | The therapeutic efficacy of Exemestane can be decreased when used in combination with Synthetic Conjugated Estrogens, B. |
| Telaprevir | The metabolism of Exemestane can be decreased when combined with Telaprevir. |
| Telithromycin | The metabolism of Exemestane can be decreased when combined with Telithromycin. |
| Telotristat ethyl | The serum concentration of Exemestane can be decreased when it is combined with Telotristat ethyl. |
| Terfenadine | The metabolism of Exemestane can be decreased when combined with Terfenadine. |
| Tetracaine | The risk or severity of methemoglobinemia can be increased when Exemestane is combined with Tetracaine. |
| Tibolone | The therapeutic efficacy of Exemestane can be decreased when used in combination with Tibolone. |
| Tipranavir | The metabolism of Exemestane can be decreased when combined with Tipranavir. |
| Troleandomycin | The metabolism of Exemestane can be decreased when combined with Troleandomycin. |
| Tucatinib | The metabolism of Tucatinib can be decreased when combined with Exemestane. |
| Venetoclax | The metabolism of Exemestane can be decreased when combined with Venetoclax. |
| Verapamil | The metabolism of Exemestane can be decreased when combined with Verapamil. |
| Viloxazine | The metabolism of Exemestane can be decreased when combined with Viloxazine. |
| Voriconazole | The metabolism of Exemestane can be decreased when combined with Voriconazole. |
| Zimelidine | The metabolism of Exemestane can be decreased when combined with Zimelidine. |
| Ziprasidone | The metabolism of Exemestane can be decreased when combined with Ziprasidone. |
Pregnancy and Lactation
US FDA pregnancy category: Not assigned
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.
Breast-feeding
It is not known if exemestane passes into breast milk. If you are breastfeeding and are taking this medication, it may affect your baby. Talk to your doctor about whether you should continue breastfeeding. The safety and effectiveness of using this medication have not been established for children.
What special precautions should I follow?
Before taking exemestane,
- tell your doctor and pharmacist if you are allergic to exemestane or any other medications.
- tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, and nutritional supplements you are taking or plan to take. Be sure to mention any of the following: carbamazepine (Carbatrol, Epitol, Tegretol); medications that contain estrogens such as hormone replacement therapy and hormonal contraceptives (birth control pills, patches, rings, and injections); phenobarbital; phenytoin (Dilantin); and rifampin (Rifadin, in Rifater, in Rifamate). Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
- tell your doctor what herbal products you are taking, especially St John’s wort.
- tell your doctor if you have or have ever had osteoporosis (a condition in which the bones are fragile and break easily), liver or kidney disease.
- tell your doctor if you are pregnant or plan to become pregnant. You will need to have a negative pregnancy test within 7 days before you begin to take exemestane. You should use birth control to avoid pregnancy during your treatment with exemestane and for 1 month after your final dose. If you become pregnant while taking exemestane, call your doctor immediately. Exemestane may harm the fetus.
- tell your doctor if you are breastfeeding. You should not breastfeed during your treatment with exemestane and for 1 month after your final dose.
References
