Anticonvulsant
PREGNANCY RECOMMENDATION: No Human Data—Animal Data Suggest Risk
BREASTFEEDING RECOMMENDATION: No Human Data—Potential Toxicity
PREGNANCY SUMMARY
No reports describing the use of perampanel in human pregnancy have been located. The animal data suggest risk, but the absence of human pregnancy experience prevents a more complete assessment of the embryo–fetal risk. If the drug is used in pregnancy, physicians are encouraged to recommend that their patient enroll in the North American Antiepileptic Drug Pregnancy Registry by calling the toll free number 1-888-233-2334. Information on the Registry can also be found at the website: http://www.aedpregnancyregistry.com.
FETAL RISK SUMMARY
Perampanel is a noncompetitive antagonist of a glutamate receptor on postsynaptic neurons. It is indicated as adjunctive therapy for the treatment of partial-onset seizures with or without secondarily generalized seizures in patients with epilepsy 12 years or older. It is extensively metabolized to apparently inactive metabolites. Plasma protein binding, mainly to albumin and α1-acid glycoprotein, is about 95%–96% and the half-life is about 105 hours (1).
Reproduction studies have been conducted in rats and rabbits. In pregnant rats during organogenesis, all doses (1, 3, or 10 mg/kg/day) tested resulted in visceral abnormalities (diverticulum of the intestine). The lowest dose was similar to the human dose of 8 mg/day based on BSA (HD). Embryo lethality and reduced fetal body weight were observed at the mid and high doses. When all doses tested were given throughout gestation and lactation, fetal and pup deaths were observed at the mid and high doses and delayed sexual maturation in males and females at the highest dose. No effects were observed on measures of neurobehavioral or reproductive function in the offspring. The no-effect dose for prenatal and postnatal developmental toxicity was similar to the HD. In pregnant rabbits given the drug throughout organogenesis at the same three doses as above, embryo lethality was observed at the mid to high doses; the no-effect dose was about 2 times the HD (1).
Long-term studies for carcinogenicity in mice and rats were negative as were the assays for mutagenicity. No clear effects on fertility were observed in male and female rats given perampanel (1, 10, or 30 mg/kg/day) before and throughout mating and continuing in females to gestation day 6. Prolonged and/or irregular estrus cycles were observed at all doses tested, but especially at the highest dose (1).
It is not known if perampanel crosses the human placenta. The molecular weight (about 349 for the nonhydrated form) and the long half-life suggest that the drug will cross to the embryo and fetus in spite of the high plasma protein binding.
BREASTFEEDING SUMMARY
No reports describing the use of perampanel during human lactation have been located.
The molecular weight (about 349 for the nonhydrated form) and the long half-life (105 hours) suggest that the drug will be excreted into breast milk in spite of the high (95%–96%) plasma protein binding. The effect of this exposure on a nursing infant is unknown. If the drug is used during breastfeeding, the infant should be monitored for some of the most common adverse reactions observed in adults, such as dizziness, somnolence, fatigue, irritability, and nausea.
Reference
1.Product information. Fycompa. Eisai, 2012.