Iptacopan 200mg capsules

Available data from clinical trials with iptacopan use in pregnant women are insufficient to identify a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. There are risks to the mother and fetus associated with untreated paroxysmal nocturnal hemoglobinuria (PNH) in pregnancy. The use of iptacopan in pregnant women or women planning to become pregnant may be considered following an assessment of the risks and benefits.

PNH in pregnancy is associated with adverse maternal outcomes, including worsening cytopenias, thrombosis, infections, bleeding, miscarriages, increased maternal mortality, and adverse fetal outcomes, including fetal death and premature delivery.
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In animal reproduction studies, oral administration of iptacopan to pregnant rats and rabbits during organogenesis at exposures 4 to 6 times the human exposure (based on AUC) at the maximum recommended human dose (MRHD) of 200 mg twice daily did not induce embryo or fetal toxicity.
[L49066]


Iptacopan was not genotoxic or mutagenic in a battery of in vitro and in vivo assays.
[L49066]


Carcinogenicity studies conducted with oral administration of iptacopan in RasH2 transgenic mice with doses up to 1,000 mg/kg/day for 6 months and in rats with doses up to 750 mg/kg/day for 2 years did not identify any carcinogenic potential. The highest exposure to iptacopan in rats corresponds to ~9 times the MRHD based on AUC.
[L49066]


In a fertility study in male rats, iptacopan did not adversely impact fertility up to the highest tested dose of 750 mg/kg/day, which corresponds to 4 times the MRHD based on AUC. Reversible effects on the male reproductive system (testicular tubular degeneration and cellular debris in epididymis) were observed in repeatdose toxicity studies with oral administration in dogs at doses ≥ 2 times the MRHD based on AUC, with no clear effects on sperm numbers, morphology, or motility.

In a fertility and early embryonic developmental study in female rats, oral administration of iptacopan caused increased pre-and post-implantation losses when given at the highest dose of 1,000 mg/kg/day orally, which corresponds to ~11 times the MRHD based on AUC.
[L49066]