CONTRAINDICATIONS
None known.
WARNINGS
Anastrozole can cause fetal harm when administered to a pregnant woman. Anastrozole has been
found to cross the placenta following oral administration of 0.1 mg/kg in rats and rabbits (about 3/4
and 1.5 times the recommended human dose, respectively, on a mg/m2 basis). Studies in both rats
and rabbits at doses equal to or greater than 0.1 and 0.02 mg/kg/day, respectively (about 3/4 and
1/3, respectively, the recommended human dose on a mg/m2 basis), administered during a period of
organogenesis showed that anastrozole increased pregnancy loss (increased pre- and/or
post-implatation loss, increased resorption, and decreased numbers of live fetuses); effects were
dose related in rats. Placental weights were significantly increased in rats at doses of 0.1 mg/kg/day
or more.
Evidence of fetotoxicity, including delayed fetal development (i.e. incomplete ossification and
depressed fetal body weights), was observed in rats administered doses of 1 mg/kg/day (which
produced plasma anastrozole CSSMAXand AUC0-24 hr that were 19 times and 9 times higher than
the respective values found in healthy post-menopausal humans at the recommended dose). There
was no evidence of teratogenicity in rats administered doses up to 1.0 mg/kg/day. In rabbits,
anastrozole caused pregnancy failure at doses equal to or greater than 1.0 mg/kg/day (about 16
times the recommended human dose on a mg/m2 basis); there was no evidence of teratogenicity in
rabbits administered 0.2 mg/kg/day (about 3 times the recommended human dose on a mg/m2
basis).
There are no adequate and well-controlled studies in pregnant women using anastrozole. If
anastrozole is used during pregnancy or if the patient becomes pregnant while receiving this drug,
the patient should be apprised of the potential hazard to the fetus or potential risk for loss of the
pregnancy.
PRECAUTIONS
General
Before starting treatment with anastrozole, pregnancy must be excluded (see WARNINGS).
Anastrozole should be administered under the supervision of a qualified physician experienced in the
use of anticancer agents.
Laboratory Tests
Three-fold elevations of mean serum gamma glutamyl transferase (GT) levels have been observed
among patients with liver metastases receiving anastrozole or megestrol acetate. These changes
were likely related to the progression of liver metastases in these patients, although other
contributing factors could not be ruled out.
Carcinogenesis
No long term studies have been conducted to assess the carcinogenic potential of anastrozole.
Mutagenesis
Anastrozole has not been shown to be mutagenic in in vitro tests (Ames and E. coli bacterial tests,
CHO-K1 gene mutation assay) or clastogenic either in vivo (chromosome aberrations in human
lymphocytes) or in in vitro (micronucleus test in rats).
Impairment of Fertility
Studies to investigate the effect of anastrozole on fertility have not been conducted; however,
chronic studies indicated hypertrophy of the ovaries and the presence of follicular cysts in rats
administered doses equal to or greater than 1 mg/kg/day (which produced plasma anastrozole
CSSMAXand AUC0-24 hr that were 19 and 9 times higher than the respective values found in
post-menopausal humans at the recommended dose). In addition, hyperplastic uteri were observed
in chronic studies of female dogs administered doses equal to or greater than 1 mg/kg/day (which
produced plasma anastrazole CSSMAXand AUC0-24 hr that were 22 times and 16 times higher than
the respective values found in post-menopausal humans at the recommended dose). It is not known
whether these effects on the reproductive organs of animals are associated with impaired fertility in
humans.
Pregnancy Category D: (see WARNINGS).
Nursing Mothers It is not known if anastrozole is excreted in human milk. Because many drugs
are excreted in human milk, caution should be exercised when anastrozole is administered to a
nursing woman (see WARNINGS and PRECAUTIONS).
Pediatric Use The safety and efficacy of anastrozole in pediatric patients have not been
established.
Geriatric Use Fifty percent of patients in studies 0004 and 0005 were 65 or older. Response rates
and time to progression were similar for the over 65 and younger patients.