IGA. Patients should be advised of possible worsening of ezogabine’s general dose-related adverse reactions if they take POTIGA with alcohol [see Clinical Pharmacology (12.3)].
7.4 Laboratory Tests
Ezogabine has been shown to interfere with clinical laboratory assays of both serum and urine bilirubin, which can result in falsely elevated readings.
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Pregnancy Category C. There are no adequate and well-controlled studies in pregnant women. POTIGA should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
In animal studies, doses associated with maternal plasma exposures (AUC) to ezogabine and its major circulating metabolite, NAMR, similar to or below those expected in humans at the maximum recommended human dose (MRHD) of 1,200 mg per day produced developmental toxicity when administered to pregnant rats and rabbits. The maximum doses eva luated were limited by maternal toxicity (acute neurotoxicity).
Treatment of pregnant rats with ezogabine (oral doses of up to 46 mg/kg/day) throughout organogenesis increased the incidences of fetal skeletal variations. The no-effect dose for embryo-fetal toxicity in rats (21 mg/kg/day) was associated with maternal plasma exposures (AUC) to ezogabine and NAMR less than those in humans at the MRHD. Treatment of pregnant rabbits with ezogabine (oral doses of up to 60 mg/kg/day) throughout organogenesis resulted in decreased fetal body weights and increased incidences of fetal skeletal variations. The no-effect dose for embryo-fetal toxicity in rabbits (12 mg/kg/day) was associated with maternal plasma exposures to ezogabine and NAMR less than those in humans at the MRHD.
Administration of ezogabine (oral doses of up to 61.9 mg/kg/day) to rats throughout pregnancy and lactation resulted in increased pre- and postnatal mortality, decreased body weight gain, and delayed reflex development in the offspring. The no-effect dose for pre- and postnatal developmental effects in rats (17.8 mg/kg/day) was associated with maternal plasma exposures to ezogabine and NAMR less than those in humans at the MRHD.
Pregnancy Registry: To provide information regarding the effects of in utero exposure to POTIGA, physicians are advised to recommend that pregnant patients taking POTIGA enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry. This can be done by calling the toll-free number 1-888-233-2334, and must be done by patients themselves. Information on the registry can also be found at the website www.aedpregnancyregistry.org.
8.2 Labor and Delivery
The effects of POTIGA on labor and delivery in humans are unknown.
8.3 Nursing Mothers
It is not known whether ezogabine is excreted in human milk. However, ezogabine and/or its metabolites are present in the milk of lactating rats. Because of the potential for serious adverse reactions in nursing infants from POTIGA, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
8.4 Pediatric Use
The safety and effectiveness of POTIGA in patients under 18 years of age have not been established.
In juvenile animal studies, increased sensitivity to acute neurotoxicity and urinary bladder toxicity was observed in young rats compared to adults. In studies in which rats were dosed starting on postnatal day 7, ezogabine-related mortality, clinical signs of neurotoxicity, and re |
