Drug-drug Interactions Between Cenobamate and Other Concomitantly Administered Medications
Abstract number :
1.42
Submission category :
7. Anti-seizure Medications / 7C. Cohort Studies
Year :
2024
Submission ID :
1168
Source :
www.aesnet.org
Presentation date :
12/7/2024 12:00:00 AM
Published date :
Authors :
Presenting Author: Anthony Jimenez, BS – Yale University School of Medicine
Chinenye Okafor, MBBS, MPH – Medical University of South Carolina
Poojith Nuthalapati, MD – Yale School of Medicine, Comprehensive Epilepsy Center, Department of Neurology
Isabel Toghramadjian, – Northwestern University
Maria Dorotan, MD – Comprehensive Epilepsy Center, Department of Neurology, Yale New Haven Hospital
Hamada Altalib, DO, MPH – Yale University School of Medicine
Lawrence Hirsch, MD – Yale University School of Medicine
Aline Herlopian, MD – Yale University
Rationale:
Cenobamate (CNB), a novel anti-seizure medication (ASM) used for medically refractory epilepsy, is known to have prominent drug-drug interactions (DDI) that can limit tolerability and lead to discontinuation. Most interactions that have been established are with other ASMs, and their clinically relevant interactions with other drug classes are not known.
Methods:
This is a retrospective single Level IV Comprehensive Epilepsy Center clinical data analysis of patients prescribed CNB from January 2020 to December 2023. We performed a descriptive analysis of DDI between CNB and commonly co-administered medications such as contraceptives, as well as lipid-lowering, antiplatelet or anticoagulant, anti-diabetic, and psychiatric medications using pre-determined clinically relevant parameters for each drug class.
Results:
Out of 98 subjects prescribed CNB from January 2020 to December 2023, 55 were excluded: 19 had no clear CNB start date or unknown stable dose, 26 had limited clinical history on chart review, and 10 were not taking any concomitant medications of interest. All 43 patients included in the analysis were taking at least one additional ASM (mean: 3 additional ASM, Figure 1), of whom 8 patients discontinued CNB. We conducted further analysis on the remaining 35 patients.
Eighteen of 35 (51.4%) patients were taking one of the lipid-lowering, anti-diabetic, or antiplatelet/anticoagulant drugs (Figure 2). Four (22.2%) were on insulin with an overall increase in HbA1c following CNB administration (compared to prior CNB; 7.7 to 11.2%; CNB stable dose at 150-200mg). Five (27.8%) were on lipid-lowering drugs; one patient showed a favorable HDL/LDL trend (61/150 to 70/91mg/dl; CNB dose at 200-250mg) and another showed a reverse effect in lipid profile (38/80 to 51/144mg/dl; CNB dose at 150-400mg). No significant trend was observed for INR values (mean 1.37-1.15 prior to CNB and 1.16-1.36 during CNB) for the 15 (83.3%) patients on anticoagulant (n=14) and antiplatelet (n=1).
Eleven of 18 (61.1%) females were on at least one form of contraceptive medication with 2 pregnancies during CNB intake, one intended (on etonogestrel implant) and the other unintended (on norelgestromine patch); CNB dose was at 200mg for both.
Eighteen of 35 (51.4%) patients were prescribed psychiatric medications prior to CNB administration. Four of these patients were hospitalized during CNB use for psychiatric episodes (CNB dose range, 100-300mg).
Conclusions:
In this small cohort, we observed significant trends inferring CNB interaction with medications of different drug classes using predetermined clinically relevant parameters. Nonetheless, the above findings must be interpreted with caution given the small sample size and retrospective nature of the study. A larger controlled cohort is necessary to draw definitive conclusions.
Funding: NA
Anti-seizure Medications