Aromasin (exemestane)
Aromatase Inhibitors Oral Tablet
Last reviewed · Source: First Databank (FDB) drug data
Overview
Exemestane, an aromatase inhibitor, is an antineoplastic agent.
Exemestane is an irreversible, selective steroidal aromatase inhibitor structurally related to the natural substrate androstenedione. Unlike nonsteroidal (type II) aromatase inhibitors (e.g., aminoglutethimide, letrozole), steroidal inhibitors such as exemestane (type I aromatase inhibitors) act as false substrates and are converted by aromatase to reactive alkylating intermediates that bind covalently to the substrate binding site of the enzyme; this binding to the active site of aromatase is irreversible, resulting in its inactivation (i.e., ''suicide'' inhibition). As a result of these differences, there appears to be a lack of cross-resistance in susceptible cancers between type I and II inhibitors.
Exemestane selectively inhibits the conversion of androgens to estrogens. Because estrogen acts as a growth factor for hormone-dependent breast cancer cells, reduction of serum and tumor concentrations of estrogen inhibits tumor growth and delays disease progression. In postmenopausal women, ovarian secretion of estrogen declines and conversion of adrenal androgens (mainly androstenedione and testosterone) to estrone and estradiol in peripheral tissues (adipose, muscle, and liver), catalyzed by the aromatase enzyme, is the principal source of estrogens.
Exemestane selectively inhibits the synthesis of estrogens and does not affect synthesis of adrenal corticosteroid, aldosterone, or thyroid hormone. In dose-ranging (0.5-800 mg) studies, 25 mg was the minimum dose to exhibit maximum suppression of plasma estrogens. A single 25-mg exemestane dose reduces plasma estrogen (estradiol, estrone, and estrone sulfate) concentrations in postmenopausal women by as much as 85-95% within 2-3 days, with maximal suppression persisting up to at least 4-5 days after dosing.
After 4-12 weeks of exemestane therapy (25 mg daily) in postmenopausal women, plasma estrogen concentrations were suppressed by an average of 91-95%, and whole body aromatization was suppressed by 98%. Although an apparently lower suppression (e.g., by 60-70%) of plasma estrogens has been reported in some studies, these studies used a less-specific assay method (i.e., RIA) than the method (i.e., HPLC) used in studies reporting higher levels of suppression.
A dose-dependent decrease in sex hormone binding globulin (SHBG) has been observed with exemestane dosages of 2.5 mg or more daily. Slight, dose-independent increases in serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) concentrations have been observed even at low dosages as a result of negative feedback on the pituitary gland. At dosages up to 25 mg daily, no clinically important effect on circulating concentrations of androstenedione, dehydroepiandrostenedione sulfate, or 17-hydroxyprogesterone and only small decreases in circulating concentrations of testosterone are observed; however, at dosages of 200 mg or more daily, testosterone and androstenedione concentrations are increased.
17-Hydroexemestane, a metabolite, exhibits substantial intrinsic androgenic activity, which may become clinically important at high (e.g., 200 mg daily) exemestane dosages.
Exemestane is rapidly absorbed following oral administration, with peak concentrations in women with breast cancer or healthy women attained within about 1.2 or 2.9 hours, respectively. Approximately 42% of an oral dose of exemestane is absorbed from the gastrointestinal tract. Following repeated doses, the mean AUC in women with breast cancer is approximately twice that in healthy women.
Administration with a high-fat meal increases the AUC and peak plasma concentration of exemestane by 59 and 39%, respectively. Exemestane is approximately 90% protein bound (mainly to alpha1-acid glycoprotein and albumin). Exemestane is extensively metabolized via CYP3A4 and aldoketoreductases; metabolites are inactive or inhibit aromatase with decreased potency compared with the parent drug.
One metabolite, 17-hydroexemestane, may have androgenic activity. Exemestane is excreted similarly (42%) in both urine and feces; <1% isexcreted as unchanged drug in urine. The half-life of exemestane is approximately 24 hours.
USES: This medication is used to treat certain types of breast cancer (such as hormone-receptor-positive breast cancer) in women after menopause. Exemestane is also used to help prevent the cancer from returning. Some breast cancers are made to grow faster by a natural hormone called estrogen.
Exemestane decreases the amount of estrogen the body makes and helps to slow or reverse the growth of these breast cancers. Exemestane is usually not used in women of childbearing age.
Generic name: exemestane
Pronunciation: (ex-em-ESS-tain)
Drug class: Aromatase Inhibitors
Therapeutic class: Antineoplastics
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Aromasin
Indications
The following indications are listed for Aromasin:
- Advanced Breast Cancer Progress Post-Antiestrogen Therapy
- Hormone Receptor Positive Postmenopausal Early Breast Cancer After Adjuvant Tamoxifen
Dosing
Strong cytochrome P-450 (CYP) 3A4 inducers may decrease exemestane exposure. The recommended dosage of exemestane when given concurrently with strong CYP3A4 inducers (e.g., rifampin (rifampicin) or phenytoin) is 50 mg once daily after a meal.
Exemestane is administered orally once daily after a meal.
Store at 25degreesC (excursions permitted between 15-30degreesC).
| Drug label | Dosing type | Instructions |
|---|---|---|
| Aromasin 25 Mg Tablet | Maintenance | Take 1 tablet (25 mg) by oral route once daily after a meal. |
| Drug label | Dosing type | Instructions |
|---|---|---|
| Exemestane 25 Mg Tablet | Maintenance | Take 1 tablet (25 mg) by oral route once daily after a meal. |
Drug interactions
Exemestane is metabolized by cytochrome P-450 isoenzyme 3A4 (CYP3A4). Exemestane does not inhibit CYP isoenzymes 1A2, 2C9, 2D6, 2E1, or 3A4.
Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.
Selected Anti-Aromatase Agents/Estrogens
SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.
MECHANISM OF ACTION: Aromatase inhibitors(1-6) and inactivators(7-10) treat breast cancer by inhibiting estrogen synthesis therefore lowering serum estrone and estradiol levels. In postmenopausal women, androgens are metabolized to estrogens via the primary pathway of the aromatase enzyme.
CLINICAL EFFECTS: Concurrent administration of estrogen may decrease the effectiveness of aromatase inhibitors.(1-6)
PREDISPOSING FACTORS: None determined.
PATIENT MANAGEMENT: The Canadian,(1) UK,(2) and US(3) manufacturers of anastrozole state that estrogen containing therapies should not be used during anastrozole therapy. The Australian,(7) Canadian,(8) UK,(9) and US(10) manufacturers of exemestane state that exemestane should not be administered with estrogen containing therapies. The Canadian(4) and UK(5) manufacturer of letrozole state that estrogen containing therapies should be avoided during letrozole therapy.
DISCUSSION: Many breast cancers have estrogen receptors and their growth can be stimulated by estrogen. Anastrozole is a potent and selective non-steroidal aromatase inhibitor that lowers serum estradiol levels. Concurrent use of estrogen may diminish the effects of anastrozole.(1-3) Exemestane is a steroidal aromatase inactivator that lowers serum estradiol levels. Concurrent use of estrogen may diminish the effects of exemestane.(7-10)
Severe Interaction: Action is required to reduce the risk of severe adverse interaction.
Exemestane/Strong Cyp3a4 Inducers
SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.
MECHANISM OF ACTION: Strong CYP3A4 inducers may induce the metabolism of exemestane.(1)
CLINICAL EFFECTS: Concurrent use of a strong CYP3A4 inducer may result in decreased levels and effectiveness of exemestane.(1)
PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks.
PATIENT MANAGEMENT: The US manufacturer of exemestane recommends that patients receiving concurrent therapy with a strong CYP3A4 inducer receive 50 mg of exemestane daily after a meal.(1) The dosage of exemestane may need to be adjusted if the inducer is discontinued.
DISCUSSION: In a study in 10 healthy postmenopausal subjects, pretreatment with rifampin (600 mg daily for 14 days) decreased the area-under-curve (AUC) and maximum concentration (Cmax) of a single dose of exemestane (25 mg) by 54% and 41%, respectively.(1) Strong inducers of CYP3A4 would be expected to decrease the AUC of a sensitive 3A4 substrate by 80% or more and include: apalutamide, barbiturates, carbamazepine, encorafenib, enzalutamide, fosphenytoin, ivosidenib, lumacaftor, mitotane, phenobarbital, phenytoin, primidone, rifampin, rifapentine and St. John's wort.(1-3) Moderate inducers of CYP3A4 would be expected to decrease the AUC of a sensitive 3A4 substrate by 50-80% and include: bosentan, efavirenz, etravirine, modafinil, nafcillin, rifabutin, and thioridazine.(2,3) Weak inducers of CYP3A4 would be expected to decrease the AUC of a sensitive 3A4 substrate by 20-50% and include: aprepitant, armodafinil, bexarotene, boceprevir, clobazam, danshen, dexamethasone, echinacea, garlic, gingko, ginseng, glycyrrhizin, nevirapine, oxcarbazepine, pioglitazone, prednisone, quercetin, raltegravir, rufinamide, sorafenib, sulfinpyrazone, telaprevir, terbinafine, ticagrelor, ticlopidine, vemurafenib, and vinblastine.(2,3)
Selected Anti-Aromatase Agents/Selected Vaginal Estrogens
SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.
MECHANISM OF ACTION: Aromatase inhibitors(1-6) and inactivators(7-10) treat breast cancer by inhibiting estrogen synthesis therefore lowering serum estrone and estradiol levels. In postmenopausal women, androgens are metabolized to estrogens via the primary pathway of the aromatase enzyme.
CLINICAL EFFECTS: Concurrent administration of estrogen may decrease the effectiveness of aromatase inhibitors.(1-6)
PREDISPOSING FACTORS: None determined.
PATIENT MANAGEMENT: The Canadian,(1) UK,(2) and US(3) manufacturers of anastrozole state that estrogen containing therapies should not be used during anastrozole therapy. The Australian,(7) Canadian,(8) UK,(9) and US(10) manufacturers of exemestane state that exemestane should not be administered with estrogen containing therapies. The Canadian(4) and UK(5) manufacturer of letrozole state that estrogen containing therapies should be avoided during letrozole therapy. A clinical consensus from the American College of Obstetricians and Gynecologists states that low-dose vaginal estrogen may be used in patients on aromatase inhibitors who have failed non-hormonal treatment after shared decision making.(11) The Fifth International Consultation on Sexual Medicine also made recommendations on treatment of genitourinary syndrome of menopause (GSM). They state that local estrogen therapy cannot be a first line treatment for GSM in women on adjuvant hormone therapy but low- and ultra-low dose local estrogens can be used after trying non-hormonal approaches, and after a discussion of risks and benefits with the patient.(12)
DISCUSSION: Many breast cancers have estrogen receptors and their growth can be stimulated by estrogen. Anastrozole is a potent and selective non-steroidal aromatase inhibitor that lowers serum estradiol levels. Concurrent use of estrogen may diminish the effects of anastrozole.(1-3) Exemestane is a steroidal aromatase inactivator that lowers serum estradiol levels. Concurrent use of estrogen may diminish the effects of exemestane.(7-10) Several meta-analyses and systematic reviews have concluded that vaginal estrogens are likely to be safe in women on aromatase inhibitors. Nevertheless, they recommend using vaginal estrogens after a trial with nonhormonal therapies has failed and following shared decision making including a discussion with the patient of the risks and benefits of treatment.(13-16)
Moderate Interaction: Assess the risk to the patient and take action as needed.
Exemestane/Selected Moderate-Weak Cyp3a4 Inducers
SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.
MECHANISM OF ACTION: CYP3A4 inducers may induce the metabolism of exemestane.(1)
CLINICAL EFFECTS: Concurrent use of a CYP3A4 inducer may result in decreased levels and effectiveness of exemestane.(1)
PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks.
PATIENT MANAGEMENT: The US manufacturer of exemestane recommends that patients receiving concurrent therapy with a strong CYP3A4 inducer receive 50 mg of exemestane daily after a meal.(1) It may be prudent to consider a dosage increase for patients receiving weaker CYP3A4 inducers.
DISCUSSION: In a study in 10 healthy postmenopausal subjects, pretreatment with rifampin (a strong CYP3A4 inducer, 600 mg daily for 14 days) decreased the area-under-curve (AUC) and maximum concentration (Cmax) of a single dose of exemestane (25 mg) by 54% and 41%, respectively.(1) Strong inducers of CYP3A4 would be expected to decrease the AUC of a sensitive 3A4 substrate by 80% or more and include: carbamazepine, enzalutamide, mitotane, phenobarbital, phenytoin, rifabutin, rifampin, and St. John's wort.(1-3) Moderate inducers of CYP3A4 would be expected to decrease the AUC of a sensitive 3A4 substrate by 50-80% and include: belzutifan, bosentan, cenobamate, dabrafenib, dipyrone, efavirenz, elagolix, etravirine, fexinidazole, lesinurad, mavacamten, mitapivat, modafinil, nafcillin, pacritinib, pexidartinib, repotrectinib, rifabutin, sotorasib, telotristat ethyl, thioridazine, and tovorafenib.(2,3) Weak inducers of CYP3A4 would be expected to decrease the AUC of a sensitive 3A4 substrate by 20-50% and include: armodafinil, aumolertinib, bexarotene, brigatinib, brivaracetam, clobazam, danshen, darolutamide, dexamethasone, dicloxacillin, echinacea, elafibranor, enasidenib, eslicarbazepine, floxacillin, garlic, gingko, ginseng, glycyrrhizin, lorlatinib, meropenem-vaborbactam, methylprednisolone, nevirapine, omaveloxolone, oritavancin, oxcarbazepine, pioglitazone, pitolisant, quercetin, relugolix, rufinamide, sarilumab, sulfinpyrazone, sunvozertinib, suzetrigine, tazemetostat, tecovirimat, terbinafine, ticlopidine, topiramate, troglitazone, vemurafenib, vinblastine, and zanubrutinib.(2,3)
Contraindications
Known hypersensitivity to exemestane or any ingredient in the formulation.
- Lactation
- Pregnancy
- Osteopenia
- Vitamin D deficiency
Adverse reactions
Adverse events reported in 10% or more of patients with early-stage breast cancer receiving exemestane include hot flushes (flashes), fatigue, arthralgia, headache, insomnia, and increased sweating. Adverse events resulting in drug discontinuance occurred in similar proportions of exemestane- and tamoxifen-treated patients.
Adverse events reported in 5% or more of patients with advanced breast cancer receiving exemestane include fatigue, nausea, and hot flushes. Most adverse events were mild to moderate in severity.
More Frequent
- Dyspnea
- Hypertension
- Lymphopenia
Less Frequent
- Acute myocardial infarction
- Angina
- Bronchitis
- Chest pain
- Edema
- Endometrial hyperplasia
- Endometrial polyps
- Fracture
- Hyperbilirubinemia
- Infection
- Lymphadenopathy
- Myocardial ischemia
- Osteoporosis
- Sinusitis
- Thromboembolic disorder
- Upper respiratory infection
Rare or Very Rare
- Abnormal hepatic function tests
- Acute generalized exanthematous pustulosis
- Cholestatic hepatitis
- Gastric ulcer
- Heart failure
- Hepatitis
- Tendon rupture
- Tenosynovitis
More Frequent
- Acute abdominal pain
- Alopecia
- Anorexia
- Arthralgia
- Drug-induced hot flash
- Fatigue
- Flu-like symptoms
- Headache disorder
- Hyperhidrosis
- Insomnia
- Nausea
- Osteopenia
- Pain
- Vomiting
Less Frequent
- Acute cognitive impairment
- Back pain
- Bone pain
- Carpal tunnel syndrome
- Constipation
- Cough
- Cramps
- Depression
- Diarrhea
- Dizziness
- Dyspepsia
- Fever
- General weakness
- Hypoesthesia
- Increased appetite
- Myalgia
- Osteoarthritis
- Pain in extremities
- Paresthesia
- Pharyngitis
- Pruritus of skin
- Rhinitis
- Skin inflammation
- Skin rash
- Symptoms of anxiety
- Urinary tract infection
- Visual changes
Rare or Very Rare
- Tendonitis
- Trigger finger
- Urticaria
Precautions
No enhanced messaging available.
Exemestane is not indicated in pediatric patients; safety and efficacy have not been established.
Exemestane may cause fetal harm if administered to pregnant women based on its mechanism of action and animal findings. There are no adequate and well-controlled studies in pregnant women. If exemestane is used during pregnancy or if the patient becomes pregnant while receiving the drug, the patient should be apprised of the potential hazard to the fetus and the potential risk for pregnancy loss.
Exemestane is distributed into milk in rats; it is not known whether exemestane is distributed into human milk. Because of the potential for serious adverse effects in nursing infants, women should be advised to discontinue nursing during exemestane therapy and for at least 1 month after discontinuance of therapy. The effects of the drug on nursing infants or on milk production are unknown.
The manufacturer makes no recommendations for dosage adjustments based on age.
No age-related alterations in the pharmacokinetics of exemestane have been identified in healthy postmenopausal women 43-68 years of age.
ICD codes
| Code | Type | Description |
|---|---|---|
| Advanced breast cancer progress post-antiestrogen therapy | ||
| C50 | ICD10CM | Malignant neoplasm of breast |
| C50.1 | ICD10CM | Malignant neoplasm of central portion of breast |
| C50.11 | ICD10CM | Malignant neoplasm of central portion of breast, female |
| C50.111 | ICD10CM | Malignant neoplasm of central portion of right female breast |
| C50.112 | ICD10CM | Malignant neoplasm of central portion of left female breast |
| C50.119 | ICD10CM | Malignant neoplasm of central portion of unspecified female breast |
| C50.21 | ICD10CM | Malignant neoplasm of upper-inner quadrant of breast, female |
| C50.211 | ICD10CM | Malignant neoplasm of upper-inner quadrant of right female breast |
| C50.212 | ICD10CM | Malignant neoplasm of upper-inner quadrant of left female breast |
| C50.219 | ICD10CM | Malignant neoplasm of upper-inner quadrant of unspecified female breast |
| C50.31 | ICD10CM | Malignant neoplasm of lower-inner quadrant of breast, female |
| C50.311 | ICD10CM | Malignant neoplasm of lower-inner quadrant of right female breast |
| C50.312 | ICD10CM | Malignant neoplasm of lower-inner quadrant of left female breast |
| C50.319 | ICD10CM | Malignant neoplasm of lower-inner quadrant of unspecified female breast |
| C50.41 | ICD10CM | Malignant neoplasm of upper-outer quadrant of breast, female |
| C50.411 | ICD10CM | Malignant neoplasm of upper-outer quadrant of right female breast |
| C50.412 | ICD10CM | Malignant neoplasm of upper-outer quadrant of left female breast |
| C50.419 | ICD10CM | Malignant neoplasm of upper-outer quadrant of unspecified female breast |
| C50.51 | ICD10CM | Malignant neoplasm of lower-outer quadrant of breast, female |
| C50.511 | ICD10CM | Malignant neoplasm of lower-outer quadrant of right female breast |
| C50.512 | ICD10CM | Malignant neoplasm of lower-outer quadrant of left female breast |
| C50.519 | ICD10CM | Malignant neoplasm of lower-outer quadrant of unspecified female breast |
| C50.61 | ICD10CM | Malignant neoplasm of axillary tail of breast, female |
| C50.611 | ICD10CM | Malignant neoplasm of axillary tail of right female breast |
| C50.612 | ICD10CM | Malignant neoplasm of axillary tail of left female breast |
| C50.619 | ICD10CM | Malignant neoplasm of axillary tail of unspecified female breast |
| C50.81 | ICD10CM | Malignant neoplasm of overlapping sites of breast, female |
| C50.811 | ICD10CM | Malignant neoplasm of overlapping sites of right female breast |
| C50.812 | ICD10CM | Malignant neoplasm of overlapping sites of left female breast |
| C50.819 | ICD10CM | Malignant neoplasm of overlapping sites of unspecified female breast |
| C50.91 | ICD10CM | Malignant neoplasm of breast of unspecified site, female |
| C50.911 | ICD10CM | Malignant neoplasm of unspecified site of right female breast |
| C50.912 | ICD10CM | Malignant neoplasm of unspecified site of left female breast |
| C50.919 | ICD10CM | Malignant neoplasm of unspecified site of unspecified female breast |
| Hormone receptor positive postmenopausal early breast cancer after adjuvant tamoxifen | ||
| C50.11 | ICD10CM | Malignant neoplasm of central portion of breast, female |
| C50.111 | ICD10CM | Malignant neoplasm of central portion of right female breast |
| C50.112 | ICD10CM | Malignant neoplasm of central portion of left female breast |
| C50.119 | ICD10CM | Malignant neoplasm of central portion of unspecified female breast |
| C50.21 | ICD10CM | Malignant neoplasm of upper-inner quadrant of breast, female |
| C50.211 | ICD10CM | Malignant neoplasm of upper-inner quadrant of right female breast |
| C50.212 | ICD10CM | Malignant neoplasm of upper-inner quadrant of left female breast |
| C50.219 | ICD10CM | Malignant neoplasm of upper-inner quadrant of unspecified female breast |
| C50.31 | ICD10CM | Malignant neoplasm of lower-inner quadrant of breast, female |
| C50.311 | ICD10CM | Malignant neoplasm of lower-inner quadrant of right female breast |
| C50.312 | ICD10CM | Malignant neoplasm of lower-inner quadrant of left female breast |
| C50.319 | ICD10CM | Malignant neoplasm of lower-inner quadrant of unspecified female breast |
| C50.41 | ICD10CM | Malignant neoplasm of upper-outer quadrant of breast, female |
| C50.411 | ICD10CM | Malignant neoplasm of upper-outer quadrant of right female breast |
| C50.412 | ICD10CM | Malignant neoplasm of upper-outer quadrant of left female breast |
| C50.419 | ICD10CM | Malignant neoplasm of upper-outer quadrant of unspecified female breast |
| C50.51 | ICD10CM | Malignant neoplasm of lower-outer quadrant of breast, female |
| C50.511 | ICD10CM | Malignant neoplasm of lower-outer quadrant of right female breast |
| C50.512 | ICD10CM | Malignant neoplasm of lower-outer quadrant of left female breast |
| C50.519 | ICD10CM | Malignant neoplasm of lower-outer quadrant of unspecified female breast |
| C50.61 | ICD10CM | Malignant neoplasm of axillary tail of breast, female |
| C50.611 | ICD10CM | Malignant neoplasm of axillary tail of right female breast |
| C50.612 | ICD10CM | Malignant neoplasm of axillary tail of left female breast |
| C50.619 | ICD10CM | Malignant neoplasm of axillary tail of unspecified female breast |
| C50.81 | ICD10CM | Malignant neoplasm of overlapping sites of breast, female |
| C50.811 | ICD10CM | Malignant neoplasm of overlapping sites of right female breast |
| C50.812 | ICD10CM | Malignant neoplasm of overlapping sites of left female breast |
| C50.819 | ICD10CM | Malignant neoplasm of overlapping sites of unspecified female breast |
| C50.91 | ICD10CM | Malignant neoplasm of breast of unspecified site, female |
| C50.911 | ICD10CM | Malignant neoplasm of unspecified site of right female breast |
| C50.912 | ICD10CM | Malignant neoplasm of unspecified site of left female breast |
| C50.919 | ICD10CM | Malignant neoplasm of unspecified site of unspecified female breast |
| Z17.0 | ICD10CM | Estrogen receptor positive status [Er+] |
| Z19.1 | ICD10CM | Hormone sensitive malignancy status |
ICD code information from First Databank (FDB).
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Last reviewed · Source: First Databank (FDB) drug data
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