AROMASIN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for AROMASIN (AROMASIN).
Irreversible steroidal aromatase inhibitor that binds to the aromatase enzyme, leading to its permanent inactivation via covalent modification. This reduces estrogen biosynthesis (primarily in peripheral tissues) by inhibiting conversion of androgens to estrogens.
| Metabolism | Primarily metabolized by CYP3A4; also undergoes reduction and oxidation pathways. The active metabolite 17-hydroexemestane is formed via reduction by aldoketoreductases. |
| Excretion | Primarily hepatic metabolism via CYP3A4 and aldoketoreductases, with 60-70% of metabolites excreted renally and 30-40% via feces. Less than 1% excreted unchanged in urine. |
| Half-life | Terminal elimination half-life is approximately 24 hours (range 20-30 hours) for exemestane, supporting once-daily dosing. Steady state achieved within 7 days. |
| Protein binding | Exemestane is approximately 90% bound to plasma proteins, primarily albumin and α1-acid glycoprotein. |
| Volume of Distribution | Volume of distribution is approximately 42 L (not weight-normalized; ~20 L/kg in standard adult), indicating extensive extravascular distribution. |
| Bioavailability | Oral bioavailability is approximately 60% (range 42-70%) with food increasing AUC by 40% compared to fasted state; therefore, take after a meal. |
| Onset of Action | Oral: Suppression of serum estradiol levels occurs within 2-3 days, with maximal suppression (to <10% of baseline) by 7-14 days of daily dosing. |
| Duration of Action | Duration of estradiol suppression persists for 48-72 hours after last dose; clinical antitumor effect requires continuous daily dosing for weeks to months. |
| Action Class | Aromatase inhibitor |
| Brand Substitutes | Xmalon 25mg Tablet, Xtane Tablet, Exmasin 25mg Tablet, Exeget 25mg Tablet, Samexa 25mg Tablet |
25 mg orally once daily after a meal
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for creatinine clearance ≥30 mL/min. Insufficient data for use in patients with creatinine clearance <30 mL/min. |
| Liver impairment | No dose adjustment required for mild to moderate hepatic impairment (Child-Pugh A or B). Not recommended in patients with severe hepatic impairment (Child-Pugh C). |
| Pediatric use | Safety and efficacy not established; not recommended for pediatric patients. |
| Geriatric use | No specific dose adjustment required; use same dose as younger adults. Monitor for adverse effects such as hot flashes, arthralgia, and fatigue. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for AROMASIN (AROMASIN).
| Breastfeeding | It is not known if exemestane is excreted in human milk. Due to potential serious adverse reactions in the nursing infant, women should not breastfeed while taking exemestane and for at least 1 month after the last dose. M/P ratio has not been established. |
| Teratogenic Risk | Exemestane is contraindicated in pregnancy. It is an aromatase inhibitor that can cause fetal harm based on its mechanism of action and animal studies. In pregnant rats, exemestane caused embryotoxicity, fetotoxicity, and increased abortion rates. No adequate human data exist. Use is not recommended in women who are or may become pregnant. If exposure occurs during the first trimester, there is a potential risk of teratogenicity; exposure in the second and third trimesters may cause fetal endocrine disruption. |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
["Pre-menopausal women unless concurrently receiving ovarian suppression therapy","Pregnancy (Category X)","Lactation","Known hypersensitivity to exemestane or any excipients"]
| Precautions | ["Increased risk of osteoporosis and bone fractures due to estrogen suppression","May cause decreases in bone mineral density; monitor bone health","Hepatic impairment: caution in moderate to severe impairment","May cause lipid abnormalities (decreased HDL, increased LDL)","Embryo-fetal toxicity: can cause fetal harm; advise pregnancy prevention"] |
| Food/Dietary | Take exemestane after a meal to increase absorption by approximately 40% compared to fasting. No specific food restrictions; grapefruit has not been reported to interact significantly. |
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| Fetal Monitoring | In women of reproductive potential, pregnancy testing should be performed prior to initiation of exemestane. Contraceptive counseling and use of effective non-hormonal contraception should be emphasized due to potential drug-drug interactions with hormonal contraceptives. During treatment, if pregnancy is suspected, immediate discontinuation and assessment is required. No routine fetal monitoring is indicated as use during pregnancy is contraindicated. |
| Fertility Effects | Exemestane can impair fertility in females. In premenopausal women, it may disrupt the hypothalamic-pituitary-ovarian axis, potentially leading to ovulation suppression or menstrual irregularities. Reversible effects on spermatogenesis have been observed in animal studies, but human data are lacking. In males, exemestane may reduce sperm count and motility. Women of childbearing potential should use effective contraception during treatment. |
| Clinical Pearls | 1. Aromasin (exemestane) is an irreversible steroidal aromatase inhibitor used in postmenopausal women with hormone receptor-positive breast cancer. 2. Unlike non-steroidal AIs (anastrozole, letrozole), exemestane has androgenic activity and may cause mild virilizing effects. 3. Contraindicated in premenopausal women unless combined with ovarian suppression. 4. Monitor bone mineral density due to increased fracture risk; consider bisphosphonates or denosumab. 5. Do not use with estrogen-containing therapies as they diminish efficacy. 6. Dose adjustment needed in moderate to severe hepatic impairment. |
| Patient Advice | Take Aromasin once daily after a meal to enhance absorption. · Common side effects include hot flashes, fatigue, joint pain, headache, insomnia, and sweating. · Report new bone pain, fractures, or symptoms of osteoporosis; calcium and vitamin D supplements may be recommended. · This drug is not for premenopausal women; if you are still having periods, you need to discuss ovarian suppression or alternative therapy. · Avoid estrogen-containing supplements or vaginal creams as they can reduce drug effectiveness. · If you miss a dose, skip it and resume next day; do not double dose. |