Aromasin

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Aromasin

Classes

Cytostatic Aromatase Inhibitors

Administration

Hazardous Drugs Classification
NIOSH 2016 List: Group 1
NIOSH (Draft) 2020 List: Table 2
Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
Use gloves to handle. Cutting, crushing, or otherwise manipulating tablets/capsules will increase exposure.

Oral Administration

Administer orally after meals.

Adverse Reactions
Severe

bone fractures / Delayed / 2.0-5.0
visual impairment / Early / 5.0-5.0
elevated hepatic enzymes / Delayed / 0-2.7
hyperbilirubinemia / Delayed / 0-0.9
thromboembolism / Delayed / 0.9-0.9
peptic ulcer / Delayed / 0.7-0.7

Moderate

hot flashes / Early / 13.0-32.9
hypertension / Early / 5.0-15.1
depression / Delayed / 6.2-13.0
dyspnea / Early / 10.0-10.0
peripheral edema / Delayed / 0-7.0
edema / Delayed / 7.0-7.0
constipation / Delayed / 5.0-5.0
confusion / Early / 2.0-5.0
chest pain (unspecified) / Early / 2.0-5.0
osteoporosis / Delayed / 4.6-4.6
endometrial hyperplasia / Delayed / 0.6-0.6
hepatitis / Delayed / Incidence not known
cholestasis / Delayed / Incidence not known
lymphopenia / Delayed / Incidence not known

Mild

fatigue / Early / 16.1-22.0
nausea / Early / 8.5-18.0
alopecia / Delayed / 2.0-15.1
arthralgia / Delayed / 2.0-14.6
headache / Early / 6.9-13.1
insomnia / Early / 11.0-12.4
hyperhidrosis / Delayed / 4.0-11.8
abdominal pain / Early / 6.0-11.0
anxiety / Delayed / 10.0-10.0
dizziness / Early / 8.0-9.7
diarrhea / Early / 4.0-9.6
back pain / Delayed / 2.0-8.6
weight gain / Delayed / 8.0-8.0
vomiting / Early / 7.0-7.0
anorexia / Delayed / 6.0-6.0
cough / Delayed / 6.0-6.0
asthenia / Delayed / 6.0-6.0
influenza / Delayed / 6.0-6.0
myalgia / Early / 5.5-5.5
dyspepsia / Early / 2.0-5.0
paresthesias / Delayed / 2.0-5.0
hypoesthesia / Delayed / 2.0-5.0
rash / Early / 2.0-5.0
fever / Early / 2.0-5.0
weakness / Early / 2.0-5.0
sinusitis / Delayed / 2.0-5.0
pharyngitis / Delayed / 2.0-5.0
rhinitis / Early / 2.0-5.0
infection / Delayed / 2.0-5.0
pruritus / Rapid / 2.0-5.0
carpal tunnel syndrome / Delayed / 2.4-2.4
muscle cramps / Delayed / 1.5-1.5
urticaria / Rapid / Incidence not known

Common Brand Names

Aromasin

Dea Class

Rx

Description

Oral, irreversible, steroidal aromatase inhibitor for early breast cancer (estrogen-receptor positive after 2 to 3 years of tamoxifen therapy) or advanced breast cancer
Lacks cross-resistance with other aromatase inhibitors or tamoxifen; more complete estrogen blockade than anastrazole or letrozole
Similar response rate to megestrol but causes less weight gain and prolongs survival

Dosage And Indications
For the treatment of breast cancer in postmenopausal women. For the treatment of advanced breast cancer in postmenopausal women whose disease has progressed following tamoxifen therapy.
NOTE: Exemestane is not indicated for the treatment of breast cancer in premenopausal women.
Oral dosage Postmenopausal females

25 mg by mouth once daily after a meal until tumor progression is evident. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Treatment with exemestane (n = 366) resulted in a similar objective response rate compared with megestrol acetate (n = 403) in postmenopausal women with advanced breast cancer and disease progression after tamoxifen in a multicenter, randomized, double-blind clinical trial (15% vs. 12.4%). The median duration of response was 76.1 weeks for patients treated with exemestane compared with 71 weeks for those who received megestrol; the median time to progression was 20.3 weeks vs. 16.6 weeks, respectively. There were too few deaths to draw conclusions regarding overall survival. In two single-arm trials, response rates for exemestane were 23.4% and 28.1%.

For the adjuvant treatment of estrogen receptor-positive early breast cancer in postmenopausal women who have already received 2 to 3 years of tamoxifen therapy, and who are switched to exemestane for completion of a total of 5 consecutive years of adjuvant hormonal therapy.
NOTE: Exemestane is not indicated for the treatment of breast cancer in premenopausal women.
Oral dosage Postmenopausal females

25 mg by mouth once daily after a meal; a dose adjustment is necessary if coadministered with potent CYP3A4 inducers. Treatment with exemestane should be continued in the absence of recurrent or contralateral breast cancer until a total of 5 years of adjuvant hormonal therapy is completed. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. In the Intergroup Exemestane Study 031 (IES), a multicenter, randomized, double-blind study (n = 4,742), conversion to exemestane hormonal therapy after 2 to 3 years of tamoxifen therapy significantly improved disease-free survival (primary outcome) when compared with 5 continuous years of tamoxifen therapy. Additionally, distant recurrence-free survival and time to contralateral breast cancer were significantly improved with exemestane therapy. Exemestane did not have a statistically significant effect on overall survival. Exemestane therapy was associated with an increase in the incidence of arthralgia, fractures, and osteoporosis. Tamoxifen-only therapy was associated with a significant increase in thromboembolic events, as well as an increase in gynecological symptoms vaginal bleeding.

For the treatment of estrogen receptor positive, HER2 negative, locally advanced or metastatic breast cancer in postmenopausal women refractory to letrozole or anastrozole, in combination with everolimus†.
NOTE: Everolimus (Afinitor) is FDA-approved for use in combination with exemestane for the treatment of hormone receptor-positive, HER2-negative advanced breast cancer in postmenopausal women who have failed treatment with letrozole or anastrozole.
Oral dosage Postmenopausal females

25 mg PO once daily plus everolimus (10 mg PO once daily). Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. In a randomized, double-blind, phase 3 clinical trial, treatment with everolimus significantly improved median investigator-assessed progression-free survival (PFS) compared with exemestane monotherapy (7.8 months vs. 3.2 months) in postmenopausal women with ER-positive, HER2-negative metastatic or locally advanced breast cancer, refractory to letrozole or anastrozole (n = 724); PFS was also significantly improved when assessed by central radiology review (11 months vs. 4.1 months). At a median follow-up time of 39.3 months, median overall survival was 31 months in patients treated with combination therapy compared with 26.6 months in those who received exemestane alone. Selected grade 3 and 4 adverse events reported more often in the combination arm included stomatitis (8% vs. less than 1%), anemia (less than 8% vs. less than 2%), hyperglycemia (less than 6% vs. less than 1%), fatigue (less than 5% vs. 1%), and dyspnea (less than 6% vs. less than 2%).

Dosing Considerations
Hepatic Impairment

The safety of chronic dosing of exemestane in patients with moderate or severe hepatic impairment has not been studied. It does not appear dosage adjustments are necessary based on experience with exemestane at repeated doses of 200 mg/day.

Renal Impairment

The safety of chronic dosing of exemestane in patients with renal impairment has not been studied. It does not appear dosage adjustments are necessary based on experience with exemestane at repeated doses of 200 mg/day.

Drug Interactions

Apalutamide: (Major) If coadministration of exemestane with apalutamide is necessary, increase the dose of exemestane to 50 mg once daily after a meal. Exemestane is a CYP3A4 substrate and apalutamide is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased exemestane exposure by 54%.
Carbamazepine: (Major) If coadministration of exemestane with carbamazepine is necessary, increase the dose of exemestane to 50 mg once daily after a meal. Exemestane is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased exemestane exposure by 54%.
Conjugated Estrogens: (Major) Avoid concomitant use of estrogens and exemestane. Estrogen-containing therapies may reduce the effectiveness of aromatase inhibitors, such as exemestane.
Conjugated Estrogens; Bazedoxifene: (Major) Avoid concomitant use of estrogens and exemestane. Estrogen-containing therapies may reduce the effectiveness of aromatase inhibitors, such as exemestane.
Conjugated Estrogens; Medroxyprogesterone: (Major) Avoid concomitant use of estrogens and exemestane. Estrogen-containing therapies may reduce the effectiveness of aromatase inhibitors, such as exemestane.
Desogestrel; Ethinyl Estradiol: (Major) Avoid concomitant use of estrogens and exemestane. Estrogen-containing therapies may reduce the effectiveness of aromatase inhibitors, such as exemestane.
Dienogest; Estradiol valerate: (Major) Avoid concomitant use of estrogens and exemestane. Estrogen-containing therapies may reduce the effectiveness of aromatase inhibitors, such as exemestane.
Drospirenone; Estetrol: (Major) Avoid concomitant use of estrogens and exemestane. Estrogen-containing therapies may reduce the effectiveness of aromatase inhibitors, such as exemestane.
Drospirenone; Estradiol: (Major) Avoid concomitant use of estrogens and exemestane. Estrogen-containing therapies may reduce the effectiveness of aromatase inhibitors, such as exemestane.
Drospirenone; Ethinyl Estradiol: (Major) Avoid concomitant use of estrogens and exemestane. Estrogen-containing therapies may reduce the effectiveness of aromatase inhibitors, such as exemestane.
Drospirenone; Ethinyl Estradiol; Levomefolate: (Major) Avoid concomitant use of estrogens and exemestane. Estrogen-containing therapies may reduce the effectiveness of aromatase inhibitors, such as exemestane.
Elagolix; Estradiol; Norethindrone acetate: (Major) Avoid concomitant use of estrogens and exemestane. Estrogen-containing therapies may reduce the effectiveness of aromatase inhibitors, such as exemestane.
Encorafenib: (Major) If coadministration of exemestane with encorafenib is necessary, increase the dose of exemestane to 50 mg once daily after a meal. Exemestane is a CYP3A substrate and encorafenib is a strong CYP3A inducer. Coadministration with another strong CYP3A inducer decreased exemestane exposure by 54%.
Enzalutamide: (Major) If coadministration of exemestane with enzalutamide is necessary, increase the dose of exemestane to 50 mg once daily after a meal. Exemestane is a CYP3A4 substrate and enzalutamide is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased exemestane exposure by 54%.
Eslicarbazepine: (Moderate) Use caution if coadministration of exemestane with eslicarbazepine is necessary, and monitor for a possible decrease in the efficacy of exemestane. Exemestane is a CYP3A4 substrate; eslicarbazepine is a moderate CYP3A4 inducer. In a pharmacokinetic interaction study (n = 10) with a strong CYP3A4 inducer, rifampicin (600 mg daily for 14 days), the mean Cmax and AUC of exemestane (single dose) decreased by 41% and 54%, respectively. The manufacturer of exemestane recommends a dose increase when concomitant use with a strong CYP3A4 inducer is necessary; recommendations are not available for moderate CYP3A4 inducers.
Esterified Estrogens: (Major) Avoid concomitant use of estrogens and exemestane. Estrogen-containing therapies may reduce the effectiveness of aromatase inhibitors, such as exemestane.
Esterified Estrogens; Methyltestosterone: (Major) Avoid concomitant use of estrogens and exemestane. Estrogen-containing therapies may reduce the effectiveness of aromatase inhibitors, such as exemestane.
Estradiol: (Major) Avoid concomitant use of estrogens and exemestane. Estrogen-containing therapies may reduce the effectiveness of aromatase inhibitors, such as exemestane.
Estradiol; Levonorgestrel: (Major) Avoid concomitant use of estrogens and exemestane. Estrogen-containing therapies may reduce the effectiveness of aromatase inhibitors, such as exemestane.
Estradiol; Norethindrone: (Major) Avoid concomitant use of estrogens and exemestane. Estrogen-containing therapies may reduce the effectiveness of aromatase inhibitors, such as exemestane.
Estradiol; Norgestimate: (Major) Avoid concomitant use of estrogens and exemestane. Estrogen-containing therapies may reduce the effectiveness of aromatase inhibitors, such as exemestane.
Estradiol; Progesterone: (Major) Avoid concomitant use of estrogens and exemestane. Estrogen-containing therapies may reduce the effectiveness of aromatase inhibitors, such as exemestane.
Estrogens: (Major) Avoid concomitant use of estrogens and exemestane. Estrogen-containing therapies may reduce the effectiveness of aromatase inhibitors, such as exemestane.
Estropipate: (Major) Avoid concomitant use of estrogens and exemestane. Estrogen-containing therapies may reduce the effectiveness of aromatase inhibitors, such as exemestane.
Ethinyl Estradiol; Norelgestromin: (Major) Avoid concomitant use of estrogens and exemestane. Estrogen-containing therapies may reduce the effectiveness of aromatase inhibitors, such as exemestane.
Ethinyl Estradiol; Norethindrone Acetate: (Major) Avoid concomitant use of estrogens and exemestane. Estrogen-containing therapies may reduce the effectiveness of aromatase inhibitors, such as exemestane.
Ethinyl Estradiol; Norgestrel: (Major) Avoid concomitant use of estrogens and exemestane. Estrogen-containing therapies may reduce the effectiveness of aromatase inhibitors, such as exemestane.
Ethynodiol Diacetate; Ethinyl Estradiol: (Major) Avoid concomitant use of estrogens and exemestane. Estrogen-containing therapies may reduce the effectiveness of aromatase inhibitors, such as exemestane.
Etonogestrel; Ethinyl Estradiol: (Major) Avoid concomitant use of estrogens and exemestane. Estrogen-containing therapies may reduce the effectiveness of aromatase inhibitors, such as exemestane.
Fosphenytoin: (Major) If coadministration of exemestane with fosphenytoin is necessary, increase the dose of exemestane to 50 mg once daily after a meal. Exemestane is a CYP3A4 substrate and fosphenytoin is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased exemestane exposure by 54%.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) If coadministration of exemestane with rifampin is necessary, increase the dose of exemestane to 50 mg once daily after a meal. Exemestane is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Coadministration with rifampin decreased exemestane exposure by 54%.
Isoniazid, INH; Rifampin: (Major) If coadministration of exemestane with rifampin is necessary, increase the dose of exemestane to 50 mg once daily after a meal. Exemestane is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Coadministration with rifampin decreased exemestane exposure by 54%.
Levonorgestrel; Ethinyl Estradiol: (Major) Avoid concomitant use of estrogens and exemestane. Estrogen-containing therapies may reduce the effectiveness of aromatase inhibitors, such as exemestane.
Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Major) Avoid concomitant use of estrogens and exemestane. Estrogen-containing therapies may reduce the effectiveness of aromatase inhibitors, such as exemestane.
Levonorgestrel; Ethinyl Estradiol; Ferrous Fumarate: (Major) Avoid concomitant use of estrogens and exemestane. Estrogen-containing therapies may reduce the effectiveness of aromatase inhibitors, such as exemestane.
Lumacaftor; Ivacaftor: (Major) If coadministration of exemestane with lumacaftor; ivacaftor is necessary, increase the dose of exemestane to 50 mg once daily after a meal. Exemestane is a CYP3A4 substrate and lumacaftor is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased exemestane exposure by 54%.
Lumacaftor; Ivacaftor: (Major) If coadministration of exemestane with lumacaftor; ivacaftor is necessary, increase the dose of exemestane to 50 mg once daily after a meal. Exemestane is a CYP3A4 substrate and lumacaftor is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased exemestane exposure by 54%.
Mitotane: (Major) If coadministration of exemestane with mitotane is necessary, increase the dose of exemestane to 50 mg once daily after a meal. Exemestane is a CYP3A4 substrate and mitotane is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased exemestane exposure by 54%.
Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Major) Avoid concomitant use of estrogens and exemestane. Estrogen-containing therapies may reduce the effectiveness of aromatase inhibitors, such as exemestane.
Norethindrone; Ethinyl Estradiol: (Major) Avoid concomitant use of estrogens and exemestane. Estrogen-containing therapies may reduce the effectiveness of aromatase inhibitors, such as exemestane.
Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Major) Avoid concomitant use of estrogens and exemestane. Estrogen-containing therapies may reduce the effectiveness of aromatase inhibitors, such as exemestane.
Norgestimate; Ethinyl Estradiol: (Major) Avoid concomitant use of estrogens and exemestane. Estrogen-containing therapies may reduce the effectiveness of aromatase inhibitors, such as exemestane.
Phenobarbital: (Major) If coadministration of exemestane with phenobarbital is necessary, increase the dose of exemestane to 50 mg once daily after a meal. Exemestane is a CYP3A4 substrate and phenobarbital is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased exemestane exposure by 54%.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Major) If coadministration of exemestane with phenobarbital is necessary, increase the dose of exemestane to 50 mg once daily after a meal. Exemestane is a CYP3A4 substrate and phenobarbital is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased exemestane exposure by 54%.
Phenytoin: (Major) If coadministration of exemestane with phenytoin is necessary, increase the dose of exemestane to 50 mg once daily after a meal. Exemestane is a CYP3A4 substrate and phenytoin is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased exemestane exposure by 54%.
Prasterone, Dehydroepiandrosterone, DHEA (Dietary Supplements): (Major) Prasterone, dehydroepiandrosterone, DHEA is converted via hydrosteroid dehydrogenases and aromatase into androstenedione, testosterone, and estradiol by peripheral tissues. Prasterone or DHEA supplements should not be given concurrently with any aromatase inhibitors, as DHEA could interfere with the pharmacologic action of the aromatase inhibitor and compromise aromatase inhibitor effectiveness. Conversely, aromatase inhibitors (e.g., aminoglutethimide, anastrozole, exemestane, letrozole, testolactone, vorozole) could interfere with biotransformation of DHEA.
Prasterone, Dehydroepiandrosterone, DHEA (FDA-approved): (Major) Prasterone, dehydroepiandrosterone, DHEA is converted via hydrosteroid dehydrogenases and aromatase into androstenedione, testosterone, and estradiol by peripheral tissues. Prasterone or DHEA supplements should not be given concurrently with any aromatase inhibitors, as DHEA could interfere with the pharmacologic action of the aromatase inhibitor and compromise aromatase inhibitor effectiveness. Conversely, aromatase inhibitors (e.g., aminoglutethimide, anastrozole, exemestane, letrozole, testolactone, vorozole) could interfere with biotransformation of DHEA.
Primidone: (Major) If coadministration of exemestane with primidone is necessary, increase the dose of exemestane to 50 mg once daily after a meal. Exemestane is a CYP3A4 substrate and primidone is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased exemestane exposure by 54%.
Relugolix; Estradiol; Norethindrone acetate: (Major) Avoid concomitant use of estrogens and exemestane. Estrogen-containing therapies may reduce the effectiveness of aromatase inhibitors, such as exemestane.
Rifampin: (Major) If coadministration of exemestane with rifampin is necessary, increase the dose of exemestane to 50 mg once daily after a meal. Exemestane is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Coadministration with rifampin decreased exemestane exposure by 54%.
Rifapentine: (Major) If coadministration of exemestane with rifapentine is necessary, increase the dose of exemestane to 50 mg once daily after a meal. Exemestane is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased exemestane exposure by 54%.
Segesterone Acetate; Ethinyl Estradiol: (Major) Avoid concomitant use of estrogens and exemestane. Estrogen-containing therapies may reduce the effectiveness of aromatase inhibitors, such as exemestane.
St. John's Wort, Hypericum perforatum: (Major) If coadministration of exemestane with St. John's Wort is necessary, increase the dose of exemestane to 50 mg once daily after a meal. Exemestane is a CYP3A4 substrate and St. John's Wort is a strong CYP3A4 inducer, although the amount of individual constituents of various St. John's Wort products may alter its inducing effects, making drug interactions unpredictable. Coadministration with another strong CYP3A4 inducer decreased exemestane exposure by 54%.

How Supplied

Aromasin/Exemestane Oral Tab: 25mg

Maximum Dosage
Adults

25 mg/day PO; if a potent CYP3A4 inducer is co-prescribed the maximum is 50 mg/day PO. Higher doses are tolerated but do not result in clinically significant increases in estrogen suppression.

Elderly

25 mg/day PO; if a potent CYP3A4 inducer is co-prescribed the maximum is 50 mg/day PO. Higher doses are tolerated but do not result in clinically significant increases in estrogen suppression.

Adolescents

Safety and efficacy have not been established.

Children

Safety and efficacy have not been established.

Mechanism Of Action

Exemestane irreversibly inhibits aromatase activity (approximately 98%) and reduces plasma estrone, estradiol and estrone sulphate levels by 85—95%. Exemestane is 150-times more potent than aminoglutethimide in inhibiting aromatase. Maximal aromatase suppresion occurs at exemestane doses of 10—25 mg. In postmenopausal women, the principal source of circulating estrogens is from the conversion of adrenal and ovarian androgens (androstenedione and testosterone) to estrogens (estrone and estradiol) by aromatase in peripheral tissues. Exemestane is structurally related to androstenedione and functions as false substrate for aromatase. Exemestane is processed to an intermediate that binds irreversibly to the active site of aromatase causing its inactivation, also known as "suicide inhibition." Non-steroidal aromatase inhibitors (e.g., anastrazole and letrozole) competitively bind to a different part of the aromatase enzyme. Exemestane has no detectable effect on adrenal biosynthesis of corticosteroids or aldosterone. Exemestane has no effect on other enzymes involved in steroid synthesis up to a concentration of at least 600-times higher than that needed to inhibit aromatase. Exemestane has a slight affinity for the androgen receptor. The binding of the 17-dihydrometabolite is 100-times that of exemestane; however, significant increases testosterone or androstenedione have only been seen at exemestane doses > 200 mg/day. A dose-dependent decrease in sex hormone binding globulin (SHBG) has been observed with doses of exemestane > 2.5 mg/day. Slight, nondose-dependent increases in serum lutenizing hormone (LH) and follicle-stimulating hormone (FSH) levels have been observed as a consequence of feedback at the pituitary level.

Pharmacokinetics

Exemestane is given orally. It is extensively distributed into tissues and is 90% bound to plasma proteins, including albumin and alpha1-acid glycoprotein. Maximal suppression of circulating endogenous estrogens occurs 2 to 3 days after beginning treatment with 25 mg/day orally and persists for 4 to 5 days. Exemestane is extensively metabolized via oxidation of the methylene group in position 6 and reduction of the 17-keto group with subsequent formation of many secondary metabolites. CYP3A4 is the principle isoenzyme involved in the oxidation. The metabolites are inactive or inhibit aromatase to a lesser degree than the parent drug. The 17-dihydrometabolite may have androgenic activity. The terminal half-life is about 24 hours.
 
Affected cytochrome P450 isoenzymes: CYP3A4
Exemestane is metabolized by CYP3A4 and aldoketoreductases. Strong inducers of CYP3A4 may significantly decrease exposure to exemestane. However, coadministration with ketoconazole, a strong CYP3A4 inhibitor, had no significant effect on exemestane exposure suggesting interactions with CYP3A4 inhibitors are unlikely. Exemestane does not inhibit any of the major CYP enzymes.
 

Oral Route

Exemestane is rapidly absorbed after oral administration; the Tmax in breast cancer patients was 1.2 hours. The bioavailability of exemestane is about 42% and is increased by approximately 40% following a high-fat breakfast. Additionally, a high-fat breakfast increased the AUC and Cmax by 59% and 39%, respectively.

Pregnancy And Lactation
Pregnancy

Pregnancy should be avoided by females of reproductive potential during treatment and for at least 1 month after the last dose. Although there are no adequately controlled studies in pregnant animals or humans, exemestane can cause fetal harm and is expected to result in adverse reproductive effects because of its mechanism of action. In animal studies following oral administration of exemestane 1 mg/kg, radioactivity related to 14-C-exemestane and its metabolites crossed the placenta of rats, with concentrations in maternal and fetal blood approximately equivalent. When rats were given exemestane from 14 days prior to mating until either days 15 or 20 of gestation, and resuming for the 21 days of lactation, an increase in placental weight was seen at approximately 1.5 times the recommended human dose on a mg/m2 basis. Increased resorptions, reduced number of live fetuses, decreased fetal weight, retarded ossification, prolonged gestation, and abnormal or difficult labor was observed at approximately 7.5 times the recommended human dose on a mg/m2 basis. In rabbits, daily doses of exemestane during organogenesis caused a decrease in placental weight at 70 times the recommended human dose on a mg/m2 basis, and in the presence of maternal toxicity, abortions, increased resorptions, and reduced fetal weight occurred at 210 times the recommended human dose on a mg/m2 basis. Fetal malformations were not seen in rats or rabbits at approximately 320 and 210 times the recommended human dose on a mg/m2 basis, respectively.

Counsel patients about the reproductive risk and contraception requirements during exemestane treatment. Exemestane can cause fetal harm if taken by the mother during pregnancy. Females should avoid pregnancy and use effective contraception during and for at least 1 month after treatment with exemestane. Females of reproductive potential should undergo pregnancy testing within 7 days prior to initiation of exemestane. Women who become pregnant while receiving exemestane should be apprised of the potential hazard to the fetus. In addition, based on animal data, exemestane treatment may result in impaired fertility or infertility in both males and females.