Pregnancy & Breastfeeding
8.1 Pregnancy Risk Summary Based on findings from animal studies and its mechanism of action, dexrazoxane can cause fetal harm when administered to pregnant women [see Clinical Pharmacology (12.1) ] . Available human data with dexrazoxane use in pregnant women is not sufficient to inform the drug-associated risk. In animal reproduction studies, dexrazoxane administration resulted in maternal toxicity and teratogenicity in rats and rabbits at doses significantly lower than the clinically recommended dose (see Data). Advise pregnant women and females of reproductive potential of the potential risk to a fetus. The background risk of major birth defects and miscarriage for the indicated population is unknown. 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. Data Animal Data Dexrazoxane resulted in maternal toxicity in rats at doses of ≥2 mg/kg (1/40 the human dose on a mg/m 2 basis) and embryotoxicity and teratogenicity at 8 mg/kg (approximately 1/10 the human dose on a mg/m 2 basis) when given daily to pregnant rats during the period of organogenesis. Teratogenic effects in the rat included imperforate anus, microphthalmia, and anophthalmia. In offspring allowed to develop to maturity, fertility was impaired in the male and female rats treated in utero during organogenesis at 8 mg/kg. In rabbits, doses of ≥5 mg/kg (approximately 1/10 the human dose on a mg/m 2 basis) daily during the period of organogenesis caused maternal toxicity and doses of 20 mg/kg (1/2 the human dose on a mg/m 2 basis) were embryotoxic and teratogenic. Teratogenic effects in the rabbit included several skeletal malformations such as short tail, rib and thoracic malformations, and soft tissue variations including subcutaneous, eye and cardiac hemorrhagic areas, as well as agenesis of the gallbladder and of the intermediate lobe of the lung.