Pregnancy & Breastfeeding
8.1 Pregnancy Risk Summary There are no adequate and well-controlled studies of ROCKLATAN ophthalmic solution or its pharmacologically active ingredients (netarsudil and latanoprost) in pregnant women to inform any drug associated risk. However, systemic exposure to netarsudil from ocular administration is low [see Clinical Pharmacology ( 12.3 ) ]. Reproduction studies of latanoprost showed embryofetal lethality in rabbits. No embryofetal lethality was observed at a dose approximately 15 times higher than the recommended human ophthalmic dose (RHOD). Intravenous administration of netarsudil to pregnant rats and rabbits during organogenesis did not produce adverse embryofetal effects at clinically relevant systemic exposures. ROCKLATAN should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Data Animal Data Netarsudil administered daily by intravenous injection to rats during organogenesis caused abortions and embryofetal lethality at doses ≥0.3 mg/kg/day (126-fold the plasma exposure at the RHOD, based on C max ). The no-observed-adverse-effect-level (NOAEL) for embryofetal development toxicity was 0.1 mg/kg/day (40-fold the plasma exposure at the RHOD, based on C max ). Netarsudil administered daily by intravenous injection to rabbits during organogenesis caused embryofetal lethality and decreased fetal weight at 5 mg/kg/day (1480-fold the plasma exposure at the RHOD, based on C max ). Malformations were observed at ≥3 mg/kg/day (1330-fold the plasma exposure at the RHOD, based on C max ), including thoracogastroschisis, umbilical hernia and absent intermediate lung lobe. The NOAEL for embryofetal development toxicity was 0.5 mg/kg/day (214-fold the plasma exposure at the RHOD, based on C max ). Reproduction studies have been performed with latanoprost in rats and rabbits. In 4 of 16 pregnant rabbits, no viable fetuses were present at a dose that was approximately 80 times higher than the RHOD. Latanoprost did not pr