ANASTROZOLE
Clinical safety rating: avoid
Contraindicated (not allowed)
Anastrozole is a selective non-steroidal aromatase inhibitor. It inhibits the conversion of androgens to estrogens in peripheral tissues, thereby reducing circulating estradiol levels. It has no intrinsic progestogenic, androgenic, or estrogenic activity.
| Metabolism | Metabolized extensively in the liver, primarily via N-dealkylation and hydroxylation, with CYP3A4 as the major enzyme involved. Minor contributions from CYP2C8 and other CYP450 isoforms. |
| Excretion | Primarily hepatic metabolism (85%): N-dealkylation, hydroxylation, and glucuronidation. Renal excretion of metabolites: ~10% unchanged drug in urine. Fecal elimination: ~10% as metabolites. |
| Half-life | Terminal elimination half-life: ~46 hours (range 30–60 hours). Clinically, steady-state reached after ~10 days; once-daily dosing maintains therapeutic concentrations. |
| Protein binding | 40% bound to plasma proteins (primarily albumin). |
| Volume of Distribution | Central Vd: ~44 L (0.6 L/kg). Large Vd indicates extensive tissue distribution. |
| Bioavailability | Oral: 83–85% (first-pass metabolism minimal). |
| Onset of Action | Oral: Clinical effect within 24–48 hours; maximal estrogen suppression by 3–4 days. |
| Duration of Action | Estrogen suppression persists for 6–10 days after last dose due to long half-life. Clinical benefit maintained with continuous daily dosing. |
1 mg orally once daily
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for GFR ≥30 mL/min; insufficient data for GFR <30 mL/min, use with caution. |
| Liver impairment | No dose adjustment for mild hepatic impairment (Child-Pugh A); moderate impairment (Child-Pugh B) use with caution; severe impairment (Child-Pugh C) contraindicated. |
| Pediatric use | Safety and efficacy not established in pediatric patients. |
| Geriatric use | No dose adjustment required based on age alone; monitor for decreased bone mineral density and increased fracture risk. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Tamoxifen may reduce anastrozole levels Estrogen-containing medications should not be used Decreases bone mineral density increasing fracture risk.
| Breastfeeding | Anastrozole is excreted into human milk; M/P ratio not established. Potential for serious adverse reactions in nursing infants (e.g., estrogen suppression). Breastfeeding is not recommended during therapy and for at least 2 weeks after the last dose. |
| Teratogenic Risk | Anastrozole is contraindicated in pregnancy. It may cause fetal harm based on its mechanism of action (aromatase inhibition, decreasing estrogen). There are no adequate human studies; animal studies show embryotoxicity and fetotoxicity. First trimester: risk of miscarriage and congenital anomalies. Second and third trimesters: risk of fetal endocrine disruption, low birth weight, and developmental abnormalities. |
■ FDA Black Box Warning
There is no FDA-mandated black box warning for anastrozole.
| Common Effects | Hot flashes |
| Serious Effects |
["Hypersensitivity to anastrozole or any of its excipients","Premenopausal women (unless part of a clinical trial or with documented ovarian suppression)","Pregnancy and lactation (Category X; known to cause fetal harm)","Severe hepatic impairment (Child-Pugh class C) - limited data, use with caution"]
| Precautions | ["Risk of osteoporosis and bone fractures due to estrogen suppression; consider bone mineral density monitoring","Ischemic cardiovascular events (e.g., myocardial infarction, angina) may be increased compared to tamoxifen","Elevated cholesterol levels; periodic lipid panel monitoring recommended","Reduction in bone mineral density with prolonged use; consider calcium and vitamin D supplementation","Potential for thromboembolic events (rare), though lower than with tamoxifen","Fatigue, headache, and joint pain are common but not usually severe"] |
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| Fetal Monitoring | Monitor pregnancy status before and during therapy. If inadvertently used, perform fetal ultrasound for growth and anatomy, assess amniotic fluid volume, and monitor for oligohydramnios. Monitor maternal bone density due to estrogen suppression. |
| Fertility Effects | Anastrozole may impair fertility in women by suppressing estrogen, leading to ovulation inhibition. Reversible upon discontinuation. In men, may reduce spermatogenesis. |
| Food/Dietary | No significant food interactions. Avoid grapefruit juice? No, anastrozole is not CYP3A4 substrate; no restriction with grapefruit. |
| Clinical Pearls | Aromatase inhibitor for hormone receptor-positive breast cancer. Monitor bone mineral density due to increased osteoporosis risk; consider bisphosphonate. Can cause joint pain and stiffness. Not effective in estrogen receptor-negative disease. Contraindicated in premenopausal women unless combined with ovarian suppression. |
| Patient Advice | Take at the same time daily with or without food. · May cause joint pain, hot flashes, or fatigue; report severe symptoms to doctor. · Regular bone density scans are needed; calcium and vitamin D supplements are recommended. · Do not take if pregnant or breastfeeding; use effective contraception if premenopausal. · Report any unusual vaginal bleeding, shortness of breath, or jaundice immediately. |