ZIOPTAN

Clinical summary

Indications and usage Refer to official label for current approved use. Dosage and administration See official label for dose guidance. Pregnancy 8.1 Pregnancy Risk Summary There are no adequate and well-controlled studies of ZIOPTAN administration in pregnant women to inform of drug-associated risks. In animal reproduction studies, intravenous administration of tafluprost to pregnant rabbits and rats throughout organogenesis resulted in embryofetal toxicities at exposures ≥5-times the human dose in rabbit and ≥2362-times the human dose in rat. (see Data). The estimated background risk of major birth defects and miscarriage for the indicated population(s) 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 defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Animal Data In embryo-fetal development studies, intravenous administration of tafluprost to pregnant rats and rabbits during organogenesis caused increases in post-implantation losses in both species and reductions in fetal body weights in rats (≥0.03 mcg/kg/day in rabbits, 5-times the maximum clinical exposure based on Cmax; ≥10 mcg/kg/day in rats, 2362-times the maximum clinical exposure based on Cmax). Tafluprost also increased the incidence of vertebral skeletal abnormalities in rats and the incidence of skull, brain and spine malformations in rabbits at these same doses. In rats, there were no adverse effects on embryo-fetal development at a dose of 3 mcg/kg/day corresponding to maternal plasma levels of tafluprost acid that were 343 times the maximum clinical exposure based on Cmax. At the no-effect dose in rabbits (0.01 mcg/kg/day), maternal plasma levels of tafluprost acid were below the lower level of quantification (20 pg/mL). In a pre- and postnatal development study, intravenous administration of tafluprost to pregnant rats during organogenesis and through birth and lactation, caused increased mortality of newborns, decreased body weights and delayed pinna unfolding in offsprings. The no observed adverse effect level was at a tafluprost intravenous dose of 0.3 mcg/kg/day which is greater than 3 times the maximum recommended clinical dose based on body surface area comparison.