mine receptorsmight result in pharmacodynamic interactions with SUNOSI. Interactions with dopaminergicdrugs have not been eva luated with SUNOSI. Use caution when concomitantly administeringdopaminergic drugs with SUNOSI.
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Pregnancy Exposure Registry
There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed toSUNOSI during pregnancy. Healthcare providers are encouraged to register pregnant patients, orpregnant women may enroll themselves in the registry by calling 1-877-283-6220 or contactingthe company at www.SunosiPregnancyRegistry.com.
Risk SummaryAvailable data from case reports are not sufficient to determine drug-associated risks of majorbirth defects, miscarriage, or adverse maternal or fetal outcomes. In animal reproductive studies,oral administration of solriamfetol during organogenesis caused maternal and fetal toxicities inrats and rabbits at doses ≥ 4 and 5 times and was teratogenic at doses 19 and ≥ 5 times,respectively, the maximum recommended human dose (MRHD) of 150 mg based on mg/m2body surface area. Oral administration of solriamfetol to pregnant rats during pregnancy andlactation at doses ≥ 7 times the MRHD based on mg/m2body surface area resulted in maternaltoxicity and adverse effects on fertility, growth, and development in offspring (see Data).
The estimated background risk of major birth defects and miscarriage for the indicatedpopulation is unknown. All pregnancies have a background risk of birth defect, loss, or otheradverse outcomes. In the U.S. general population, the estimated background risks of major birthefects and miscarriage in clinically recognizedpregnancies are 2% to 4% and 15% to 20%,respectively.
Data
Animal Data
Solriamfetol was administered orally to pregnant rats during the period of organogenesis at 15,67, and 295 mg/kg/day, which are approximately 1, 4, and 19 times the MRHD based on mg/m2body surface area. Solriamfetol at ≥ 4 times the MRHD caused maternal toxicity that included hyperactivity, significant decreases in body weight, weight gain, and food consumption. Fetaltoxicity at these maternally toxic doses included increased incidence of early resorption and postimplantationloss, and decreased fetal weight. Solriamfetol was teratogenic at 19 times theMRHD; it increased the incidence of fetal malformations that included severe sternebrae malalignment,hindlimb rotation, bent limb bones, and situs inversus. This dose was also maternallytoxic. The no-adverse-effect level for malformation is 4 times and for maternal and embryofetaltoxicity is approximately 1 times the MRHD based on mg/m2 body surface area.
Solriamfetol was administered orally to pregnant rabbits during the period of organogenesis at
17, 38, and 76 mg/kg/day, which are approximately 2, 5, and 10 times the MRHD based onmg/m2 body surface area. Solriamfetol at 10 times the MRHD caused maternal toxicity of bodyweight loss and decreased food consumption. Solriamfetol was teratogenic at ≥ 5 times theMRHD, it caused fetal skeletal malformation (slight-to-moderate sternebrae mal-alignment) anddecreased fetal weight. The no-adverse-effect level for malformation and fetal toxicity isapproximately 2 times and for maternal toxicity is approximately 5 times the MRHD based onmg/m2 body surface area.
Solriamfetol was administered orally to pregnant rats during the period of organogenesis fromge |
