anastrozole (Rx)

>10%

Hot flashes (12-36%)

Vasodilation (25-36%)

Fatigue (19%)

Mood disturbances (19%)

Nausea and vomiting (19%)

Weakness (16-19%)

Arthritis (17%)

Pain (17%)

Arthralgia (2-15%)

Pharyngitis (14%)

Depression (13%)

Hypertension (2-13%)

Bone pain (11%)

Increased cough (11%)

Osteoporosis (11%)

Rash (8-11%)

1-10%

Accidental injury (10%)

Back pain (10%)

Fracture (10%)

Headache (10%)

Insomnia (10%)

Peripheral edema (10%)

Dyspnea (8-10%)

Abdominal pain (9%)

Infection (9%)

Lymphedema (9%)

Diarrhea (8-9%)

Constipation (7-9%)

Breast pain (8%)

Dizziness (8%)

Urinary tract infection (8%)

Chest pain (7%)

Dyspepsia (7%)

Paresthesia (5-7%)

Anxiety (6%)

Cataracts (6%)

Flu syndrome (6%)

Sinusitis (6%)

Vulvovaginitis (6%)

Xerostomia (6%)

Breast neoplasm (5%)

Bronchitis (5%)

Cyst (5%)

Diaphoresis (5%)

Neoplasm (5%)

Vaginal bleeding (5%)

Fractures of spine, hip, or wrist (4%)

Ischemic cardiovascular disease (4%)

Vaginal hemorrhage (4%)

Vaginitis (4%)

Leukorrhea (3-4%)

Deep vein thrombosis (2%)

Endometrial cancer (intact uterus at baseline) (2%)

Ischemic cerebrovascular event (2%)

Weight gain (2%)

Lethargy (1%)

Postmarketing Reports

Hepatitis; increased alkaline phosphatase, aminotransferases, gamma-glutamyl transferase, and bilirubin

Allergic reactions, including angioedema, urticaria, and anaphylaxis

Rash, including mucocutaneous disorders (eg, erythema multiforme, Stevens-Johnson syndrome)

Myalgia, trigger finger, and hypercalcemia (with or without increase in parathyroid hormone)

Contraindications

Hypersensitivity

May cause fetal harm or loss; use is contraindicated in women who are or may become pregnant

Cautions

Increased incidence of ischemic cardiovascular events in women with preexisting ischemic heart disease; use only if benefits greatly outweigh risks

Decreases lumbar spine and total hip bone mineral density; increased risk of fractures and osteoporosis; concurrent use with bisphosphonates may be useful in patients at risk for fractures; follow available guidelines for bone mineral density management in postmenopausal women; patients with preexisting osteopenia are at higher risk for developing osteoporosis

Elevated serum cholesterol reported; monitor closely; use with caution in patients with hyperlipidemias; monitor and manage cholesterol levels with current guidelines for patients with LDL elevations

Affords no clinical benefit to premenopausal women with breast cancer

Increased risk of ischemic cardiovascular events in patients with pre-existing ischemic cardiac disease

Pregnancy

Based on findings from animal studies and mechanism of action, therapy may cause fetal harm when administered to pregnant woman; there are no studies on use in pregnant women

Advise pregnant women and females of reproductive potential of potential risk to a fetus

Verify pregnancy status of females of reproductive potential prior to initiation of therapy

Based on animal studies, therapy can cause fetal harm when administered to a pregnant woman

Advise females of reproductive potential to use effective contraception during treatment and for at least 3 weeks after last dose

Based on studies in female animals, treatment may impair fertility in females of reproductive potential

Animal data

• Anastrozole caused embryo-fetal toxicities in rats at maternal exposure that were 9 times the human clinical exposure, based on area under the curve (AUC); in rabbits, anastrozole caused pregnancy failure at doses equal to or greater than 16 times the recommended human dose on a mg/m2 basis

Lactation

There are no data on presence of drug or metabolites in human milk, or effects on breast-fed child or on milk production; because many drugs are excreted in human milk and because of tumorigenicity shown for anastrozole in animal studies, or potential for serious adverse reactions in breast-fed child from treatment, advise lactating women not to breastfeed during treatment and for 2 weeks after last dose

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Selective nonsteroidal aromatase inhibitor; prevents conversion of androstenedione to estrone and estradiol in peripheral tissues, thereby significantly lowering serum estradiol concentrations; has no effect on adrenal corticosteroids or aldosterone

Absorption

Peak plasma concentration: 2 hr without food; 5 hr with food

Onset: 24 hr (70% reduction); 2 weeks (80% reduction)

Time to steady-state levels: 7 days

Distribution

Protein bound: 40%

Metabolism

Metabolized in liver via N-dealkylation, hydroxylation, and glucuronidation (85%)

Metabolite: Triazole (inactive)

Enzymes inhibited: CYP1A2, CYP2C9, CYP3A4 (at high concentrations; inhibition not significant at usual dose)

Elimination

Half-life: 50 hr

Dialyzable: Yes

Excretion: Urine (10%)