Authors :
Presenting Author: Ilo Leppik, MD – University of Minnesota
Silvia Illamoila, Pharm D, PhD – Research Associate, University of minnesota; Angela Birnbaum, PhD – Professor, College of pharmacy, University of Minnesota; Yuhan Long, BS, BSChE – graduate student, Unicersity of minnesota; Rory Remmel, PhD – Professor, College of Pharmacy, University of Minnesota; Thaddeus Walckzack, MD – Professor, Neurology, University of Minnesota
Rationale:
Perampanel (PER) is an antiseizure medication (ASM) intensively metabolized by CYP3A4 and to a smaller extent, 3A4-5. PER is often used in combination with other ASMs and its levels can be significantly altered if other ASMs are added or subtracted from the therapeutic regimen. Monitoring ASM levels is key to providing the best personalized care for persons with epilepsy. This study was done to report PER levels observed in an epilepsy clinic.
Methods:
The Epic records from 6-28-2021 to 6-27-2022 were searched for patients prescribed PER. PER levels were obtained through two commercial laboratories (NMS and ARUP) using LC-MS. Blood levels were obtained as part of clinical practice to deliver personalized care.
Results:
There were a total of 165 patients prescribed PER. Of these, 14 were taking two different doses and six were taking suspension. These excluded from further reporting. One patient was prescribed 16 mg/day, had a blood level of only 270 ng/ml, had missing data, and was declared non-adherent, and dropped from further analysis. There were 87 (60%) female and 58 (40%) male patients. The median (range) age was 44 years (5 to 86 years). Median (range) of prescribed doses was 6 mg/day (2 to 12 mg/day). Number of ASM comedications available for analysis were one to four, excluding prn ASMs. Forty patients had at least one PER level measured. There was a wide range of PER levels for each dose, but overall there was a dose/level relationship; as doses increased, so did levels. PER levels ranged from 120 ng/ml to 1600 ng/ml. The highest level was in a 71 year old woman on three ASMs (no inducers) and a dose of 10 mg/day. Eight months later, on the same regimen, the level was 960ng/ml. For the 6 mg/day dose, the mean level was 425 ng/ml (range 390-440), for the 8 mg dose mean was 421 mg/ml (range 190-790), and for the 10 mg dose mean was 643 ng/ml (range 200-1600).
Conclusions:
Knowing the individual therapeutic concentration for an individual when they have attained a desired therapeutic outcome is important and can be informative at particular times during treatment. There was a very wide range of dose-level relationships, and thus the PER level cannot be easily predicted from the dose. It appeared that persons on inducers had the lower levels. Obtaining a blood level at the time of increased seizures is key to determining if drug adherence, formulation change, or alteration in seizure threshold needs to be considered. Measurement of ASM concentration can aid in determination of which one may be responsible for observed toxicity. PER is a complicated ASM with potential for many drug-drug interactions. Effect of age and pregnancy on its levels has not been studied. Further studies are needed to better characterize PER which has a novel mechanism and complicated pharmacokinetic properties.
Funding:
MacMillan Epilepsy Innovation Fund