Givinostat Interactions

Pregnancy & Breastfeeding

8.1 Pregnancy Risk Summary DUVYZAT is indicated for the treatment of DMD, which is a disease of predominantly young male patients. Therefore, there are no adequate data available to assess the use of DUVYZAT in pregnant women. In animal studies, oral administration of givinostat during organogenesis resulted in decreased fetal body weight and increased structural variations; oral administration during pregnancy and lactation resulted in increased embryofetal and offspring mortality and neurobehavioral changes in the offspring. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Data Animal Data Oral administration of givinostat (0, 40, 80, or 160 mg/kg/day) to pregnant rats throughout organogenesis resulted in reduced fetal body weight at the highest dose tested and increases in the incidence of skeletal and visceral variations at the mid and high doses. The no-effect dose (40 mg/kg/day) for adverse effects on embryofetal development was associated with maternal plasma exposures (AUC) lower than that in humans at the maximum recommended human dose (MRHD) of 53.2 mg twice daily. Oral administration of givinostat (0, 40, 80, or 160 mg/kg/day) to pregnant rabbits throughout organogenesis resulted in maternal death at the highest dose tested, resulting in too few fetuses to evaluate. No adverse effects on embryofetal development were observed at the low and mid doses. Plasma exposures (AUC) at the higher no-effect dose (80 mg/kg) for adverse effects on embryofetal development were approximately 4 times that in humans at the MRHD. Oral administration of givinostat (0, 40, 80, or 160 mg/kg/day) to rats throughout pregnancy and lactation resulted in increases in embryofetal mortality, stillbirths, and offspring mortality at the highest dose tested. When offspring were tested postweaning (postnatal day 49), adverse effects on behavior (decreased open field