No

Antineoplastic Agent, Miscellaneous

Treatment of advanced breast cancer in postmenopausal women with disease progression following tamoxifen therapy. Patients with ER-negative disease and patients who did not respond to tamoxifen therapy rarely responded to anastrozole.

D

Clinical effects on the fetus: Anastrozole can cause fetal harm when administered to a pregnant woman

Hypersensitivity to any component; pregnancy

Use with caution in patients with hyperlipidemias; mean serum total cholesterol and LDL cholesterol occurs in patients receiving anastrozole

>5%:

Cardiovascular: Flushing

Gastrointestinal: Little to mild nausea (10%), vomiting

Neuromuscular & skeletal: Increased bone and tumor pain

2% to 5%:

Cardiovascular: Hypertension

Central nervous system: Somnolence, confusion, insomnia, anxiety, nervousness, fever, malaise, accidental injury

Dermatologic: Hair thinning, pruritus

Endocrine & metabolic: Breast pain

Gastrointestinal: Weight loss

Genitourinary: Urinary tract infection

Local: Thrombophlebitis

Neuromuscular & skeletal: Myalgia, arthralgia, pathological fracture, neck pain

Respiratory: Sinusitis, bronchitis, rhinitis

Miscellaneous: Flu-like syndrome, infection

Symptoms of overdose include severe irritation to the stomach (necrosis, gastritis, ulceration and hemorrhage)

There is no specific antidote; treatment must be symptomatic. Vomiting may be induced if the patient is alert. Dialysis may be helpful because anastrozole is not highly protein bound. General supportive care, including frequent monitoring of all vital signs and close observation.

CYP3A3/4 enzyme substrate; CYP1A2, 2C8, 2C9, and 3A3/4 enzyme inhibitor

Potent and selective nonsteroidal aromatase inhibitor. It significantly lowers serum estradiol concentrations and has no detectable effect on formation of adrenal corticosteroids or aldosterone. In postmenopausal women, the principal source of circulating estrogen is conversion of adrenally generated androstenedione to estrone by aromatase in peripheral tissues.

Absorption: Well absorbed from GI tract; food does not affect absorption

Protein binding, plasma: 40%

Metabolism: Extensively in the liver

Half-life: 50 hours

Elimination: Primarily via hepatic metabolism (85%) and to a lesser extent renal excretion (11%)

Breast cancer: Adults: Oral (refer to individual protocols): 1 mg once daily

Dosage adjustment in hepatic impairment: Plasma concentrations in subjects with hepatic cirrhosis were within the range concentrations in normal subjects across all clinical trials; therefore, no dosage adjustment is needed

Lab test abnormalities: GGT, AST, ALT, alkaline phosphatase, total cholesterol and LDL increased; threefold elevations of mean serum GGT levels have been observed among patients with liver metastases. These changes were likely related to the progression of liver metastases in these patients, although other contributing factors could not be ruled out. Mean serum total cholesterol levels increased by 0.5 mmol/L among patients.

Drowsiness, confusion, insomnia, and anxiety are common

None reported

No information available to require special precautions

No effects or complications reported

Take as prescribed. Maintain adequate hydration (2-3 L/day of fluids unless instructed to restrict fluid intake) and nutrition. If experiencing nausea, vomiting, or anorexia, small frequent meals, frequent mouth care, sucking lozenges, or chewing gum may help or contact prescriber for relief. This medication may cause dizziness and fatigue (use caution when driving or engaging in tasks that require alertness until response to drug is known); or increased bone pain (contact prescriber for analgesia). Report swelling of extremities, chest pain or palpitations, acute headache or dizziness, increased muscle pain or weakness, CNS changes (eg, confusion, insomnia, nervousness), breast or pelvic pain, unusual bruising or bleeding, flu-like symptoms, or respiratory difficulty. Pregnancy/breast-feeding precautions: Consult prescriber if pregnant or breast-feeding.

Use with caution in patients with hyperlipidemias; mean serum total cholesterol and LDL cholesterol occurs in patients receiving anastrozole

Tablet: 1 mg

Dowsett M, Lonning PE, and Lnning PE, "Anastrozole - A New Generation in Aromatase Inhibition: Clinical Pharmacology," Oncology, 1997, 54(Suppl 2):11-4.

Goss PE and Tye LM, "Anastrozole: A New Selective Nonsteroidal Aromatase Inhibitor," Oncology, 1997, 11(11):1697-703.

Jonat W, "Clinical Overview of Anastrozole - A New Selective Oral Aromatase Inhibitor," Oncology, 1997, 54(Suppl 2):15-8.

Kelloff GJ, Lubet RA, Lieberman R, et al, "Aromatase Inhibitors as Potential Cancer Chemopreventatives," Cancer Epidemiol Biomarkers Prev, 1998, 7(1):65-78.

Silverstein MJ, "Recent Advances: Diagnosis and Treatment of Early Breast Cancer," BMJ, 1997, 314(7096):1736-9.