Anastrozole
Anastrozole Prescribing Information
Warnings and Precautions, Embryo-Fetal Toxicity (
5.4 Embryo-Fetal ToxicityBased on findings from animal studies and its mechanism of action, anastrozole tablets can cause fetal harm when administered to a pregnant woman. 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/m2basis. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during therapy with anastrozole tablets and for at least 3 weeks after the last dose
Anastrozole tablets are aromatase inhibitors indicated for:
- Adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer ()
1.1 Adjuvant TreatmentAnastrozole tablets are indicated for adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer.
- First-line treatment of postmenopausal women with hormone receptor-positive or hormone receptor unknown locally advanced or metastatic breast cancer ()
1.2 First-Line TreatmentAnastrozole tablets are indicated for the first-line treatment of postmenopausal women with hormone receptor-positive or hormone receptor unknown locally advanced or metastatic breast cancer.
- 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 previous tamoxifen therapy rarely responded to anastrozole tablets ()
1.3 Second-Line TreatmentAnastrozole tablets are indicated for the 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 previous tamoxifen therapy rarely responded to anastrozole tablets.
One 1 mg tablet taken once daily (
2.1 Recommended DoseThe dose of anastrozole tablets are one 1 mg tablet taken once a day. For patients with advanced breast cancer, anastrozole tablets should be continued until tumor progression. Anastrozole tablets can be taken with or without food.
For adjuvant treatment of early breast cancer in postmenopausal women, the optimal duration of therapy is unknown. In the ATAC trial, anastrozole tablets were administered for five years.
No dosage adjustment is necessary for patients with renal impairment or for elderly patients.
The tablets are white, round, film-coated containing 1 mg of anastrozole. The tablets are debossed with “AN” and “1” on one side and plain surface on the other side.
- Lactation: Do not breastfeed. ()
8.2 LactationRisk Summary
There are no data on the presence of anastrozole or its metabolites in human milk, or its effects on the breast-fed child or on milk production. Because many drugs are excreted in human milk and because of the tumorigenicity shown for anastrozole in animal studies, or the potential for serious adverse reactions in the breast-fed child from anastrozole tablets, advise lactating women not to breastfeed during treatment with anastrozole tablets and for 2 weeks after the last dose. - Females and Males of Reproductive Potential: Verify pregnancy status prior to initiation of anastrozole tablets. ()
8.3 Females and Males of Reproductive PotentialPregnancy Testing
Verify the pregnancy status of females of reproductive potential prior to initiation of anastrozole tablets.ContraceptionFemales
Based on animal studies, anastrozole tablets can cause fetal harm when administered to a pregnant woman[see Use in Specific Populations (8.1)].Advise females of reproductive potential to use effective contraception during treatment with anastrozole tablets and for at least 3 weeks after the last dose.InfertilityFemalesBased on studies in female animals, anastrozole tablets may impair fertility in females of reproductive potential
[see Nonclinical Toxicology (13.1)]. - Pediatric patients: Efficacy has not been demonstrated for pubertal boys of adolescent age with gynecomastia or girls with McCune-Albright Syndrome and progressive precocious puberty. ()
8.4 Pediatric UseClinical studies in pediatric patients included a placebo-controlled trial in pubertal boys of adolescent age with gynecomastia and a single-arm trial in girls with McCune-Albright Syndrome and progressive precocious puberty. The efficacy of anastrozole tablets in the treatment of pubertal gynecomastia in adolescent boys and in the treatment of precocious puberty in girls with McCune-Albright Syndrome has not been demonstrated.
Gynecomastia Study
A randomized, double-blind, placebo-controlled, multi-center study enrolled 80 boys with pubertal gynecomastia aged 11 to 18 years. Patients were randomized to a daily regimen of either anastrozole tablets 1 mg or placebo. After 6 months of treatment there was no statistically significant difference in the percentage of patients who experienced a ≥50% reduction in gynecomastia (primary efficacy analysis). Secondary efficacy analyses (absolute change in breast volume, the percentage of patients who had any reduction in the calculated volume of gynecomastia, breast pain resolution) were consistent with the primary efficacy analysis. Serum estradiol concentrations at Month 6 of treatment were reduced by 15.4% in the anastrozole tablets group and 4.5% in the placebo group.Adverse reactions that were assessed as treatment-related by the investigators occurred in 16.3% of the Anastrozole tablets -treated patients and 8.1% of the placebo-treated patients with the most frequent being acne (7% Anastrozole tablets and 2.7% placebo) and headache (7% anastrozole tablets and 0% placebo); all other adverse reactions showed small differences between treatment groups. One patient treated with anastrozole tablets discontinued the trial because of testicular enlargement. The mean baseline-subtracted change in testicular volume after 6 months of treatment was + 6.6 ± 7.9 cm3in the anastrozole tablets -treated patients and + 5.2 ± 8.0 cm3in the placebo group.
McCune-Albright Syndrome Study
A multi-center, single-arm, open-label study was conducted in 28 girls with McCune-lbright Syndrome and progressive precocious puberty aged 2 to <10 years. All patients received a 1 mg daily dose of anastrozole tablets. The trial duration was 12 months. Patients were enrolled on the basis of a diagnosis of typical (27/28) or atypical (1/27) McCune-Albright Syndrome, precocious puberty, history of vaginal bleeding, and/or advanced bone age. Patients’ baseline characteristics included the following: a mean chronological age of 5.9 ± 2.0 years, a mean bone age of 8.6 ± 2.6 years, a mean growth rate of 7.9 ± 2.9 cm/year and a mean Tanner stage for breast of 2.7 ± 0.81. Compared to pre-treatment data there were no on-treatment statistically significant reductions in the frequency of vaginal bleeding days, or in the rate of increase of bone age (defined as a ratio between the change in bone age over the change of chronological age). There were no clinically significant changes in Tanner staging, mean ovarian volume, mean uterine volume and mean predicted adult height. A small but statistically significant reduction of growth rate from 7.9 ± 2.9 cm/year to 6.5 ± 2.8 cm/year was observed but the absence of a control group precludes attribution of this effect to treatment or to other confounding factors such as variations in endogenous estrogen levels commonly seen in McCune-Albright Syndrome patients.Five patients (18%) experienced adverse reactions that were considered possibly related to anastrozole tablets. These were nausea, acne, pain in an extremity, increased alanine transaminase and aspartate transaminase, and allergic dermatitis.
Pharmacokinetics in Pediatric Patients
Following 1 mg once daily multiple administration in pediatric patients, the mean time to reach the maximum anastrozole concentration was 1 hr. The mean (range) disposition parameters of anastrozole in pediatric patients were described by a CL/F of 1.54 L/h (0.77-4.53 L/h) and V/F of 98.4 L (50.7-330.0 L). The terminal elimination half-life was 46.8 h, which was similar to that observed in postmenopausal women treated with anastrozole for breast cancer. Based on a population pharmacokinetic analysis, the pharmacokinetics of anastrozole was similar in boys with pubertal gynecomastia and girls with McCune-Albright Syndrome.
Anastrozole tablets are contraindicated in any patient who has shown a hypersensitivity reaction to the drug or to any of the excipients. Observed reactions include anaphylaxis, angioedema, and urticaria
6.2 Post-Marketing ExperienceThese adverse reactions are reported voluntarily from a population of uncertain size. Therefore, it is not always possible to estimate reliably their frequency or establish a causal relationship to drug exposure. The following have been reported in post-approval use of anastrozole tablets:
• Hepatobiliary events including increases in alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, gamma-GT, and bilirubin; hepatitis
• Rash including cases of mucocutaneous disorders such as erythema multiforme and Stevens-Johnson syndrome
• Cases of allergic reactions including angioedema, urticaria and anaphylaxis
• Myalgia, trigger finger and hypercalcemia (with or without an increase in parathyroid hormone)