Dutasteride

Contraindications

4 CONTRAINDICATIONS Dutasteride is contraindicated for use in: Pregnancy. Dutasteride use is contraindicated in women who are pregnant. In animal reproduction and developmental toxicity studies, dutasteride inhibited development of male fetus external genitalia. Therefore, dutasteride may cause fetal harm when administered to a pregnant woman [see Warnings and Precautions (5.4), Use in Specific Populations (8.1)] . Patients with previously demonstrated clinically significant hypersensitivity (e.g., serious skin reactions, angioedema) to dutasteride or other 5 alpha-reductase inhibitors [see Adverse Reactions (6.2)] . Pregnancy. Dutasteride use is contraindicated in women who are pregnant. (4, 5.4, 8.1) Patients with previously demonstrated, clinically significant hypersensitivity (e.g., serious skin reactions, angioedema) to dutasteride or other 5 alpha-reductase inhibitors. (4)

Pregnancy & Breastfeeding

8.1 Pregnancy Risk Summary Dutasteride is contraindicated for use in pregnancy because it may cause harm to the male fetus [see Contraindications (4) ]. Dutasteride is not indicated for use in women. Dutasteridem is a 5 alpha-reductase inhibitor that prevents conversion of testosterone to dihydrotestosterone (DHT), a hormone necessary for normal development of male genitalia. Abnormalities in the genitalia of male fetuses is an expected physiological consequence of inhibition of this conversion. These results are similar to observations in male infants with genetic 5 alpha-reductase deficiency. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. In animal reproduction studies, dutasteride inhibited normal development of external genitalia in male offspring when given to rats or rabbits during organogenesis at less than the maximum recommended human dose (MRHD) of 0.5 mg daily, in the absence of maternal toxicity. At 15 times the MRHD, prolonged pregnancy, decreased reproductive organ weights, and delayed puberty in male offspring were observed in rats, with no-effect levels less than the MRHD of 0.5 mg daily. Increased placental weights in rabbits were also observed, with no-effect levels less than the MRHD of 0.5 mg daily (see Data). Although dutasteride is secreted into human semen, the drug concentration in the human female partner is approximately 100 times less than concentrations producing abnormalities of male genitalia in animal studies (see Data). In monkeys dosed during organogenesis at blood concentrations comparable to or above levels to which a human female partner is estimated to be exposed, male offspring external genitalia was not adversely affected. No feminization occurred in male offspring of untreated female rats mated to treated male rats even though detectable blood levels of dutasteride were observed in the female rat