Agrylin Use In Pregnancy & Lactation

Pregnancy: Risk Summary: Available data from case reports with AGRYLIN use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. In animal embryo-fetal studies, delayed fetal development (delayed skeletal ossification and reduced body weight) was observed in rats administered anagrelide hydrochloride during organogenesis at doses approximately 97 times the maximum clinical dose (10 mg/day) based on body surface area (see Data as follows). There are adverse effects on maternal and fetal outcomes associated with thrombocythemia in pregnancy (see Clinical Considerations as follows).
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defect and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Clinical Considerations: Disease-associated maternal and/or embryo/fetal risk: Thrombotic events, such as stroke, deep vein thrombosis, or myocardial infarction, can be complications of thrombocythemia. Thrombocythemia in pregnancy is associated with an increased risk for miscarriage, stillbirth, and other maternal outcomes, such as preeclampsia.
Data: Animal Data: Anagrelide hydrochloride was administered orally to pregnant rats and rabbits during the period of organogenesis at doses up to 900 mg/kg/day in rats and up to 20 mg/kg/day in rabbits (875 and 39 times, respectively, the maximum clinical dose of 10 mg/day based on body surface area). In rats, developmental delays were observed including reductions in fetal weight at 300 and 900 mg/kg/day and delays in skeletal ossification at doses of 100 mg/kg/day and higher. The dose of 100 mg/kg/day (600 mg/m²/day) in rats is approximately 97 times the maximum clinical dose based on body surface area. No adverse embryo-fetal effects were detected in rabbits at the highest dose of 20 mg/kg/day (39 times the maximal clinical dose based on body surface area).
In a pre- and post-natal study conducted in female rats, anagrelide hydrochloride administered at oral doses of 60 mg/kg/day (58 times the maximum clinical dose based on body surface area) or higher during organogenesis through lactation produced delay or blockage of parturition, deaths of non-delivering pregnant dams and their fully developed fetuses, and increased mortality in the pups born.
In a placental transfer study, a single oral dose of [¹⁴C]-anagrelide hydrochloride (3 mg/kg) was administered to pregnant rats on gestation Day 17. Drug-related radioactivity was detected in maternal and fetal tissue.
Lactation: Risk Summary: There is no information regarding the presence of anagrelide in human milk, the effect on the breastfed child, or the effects on milk production. Anagrelide or its metabolites have been detected in the milk of lactating rats (see Data as follows). Because of the potential for serious adverse reactions, including thrombocytopenia, in a breastfed child, advise patients that breastfeeding is not recommended during treatment with AGRYLIN, and for one week following the last dose.
Data: In a rat milk secretion study, a single oral dose of [¹⁴C]-anagrelide hydrochloride (3 mg/kg) was administered to lactating female rats on postnatal Day 10. Drug-related radioactivity was detected in the maternal milk and blood.
Females and Males of Reproductive Potential: Infertility: Females: Based on findings from animal studies, AGRYLIN may impair female fertility [see Pharmacology: Toxicology: Nonclinical Toxicology: Carcinogenesis, Mutagenesis, Impairment of Fertility under Actions].