Dose Adjustment of Concomitant Antiseizure Medications During Cenobamate Treatment: Expert Opinion Consensus Recommendations.

Autor: Smith MC; Department of Neurological Sciences, Section of Clinical Neurophysiology and Epilepsy, Rush Medical College, 1725 W. Harrison Street, Suite 885, Chicago, IL, 60612, USA. michael_c_smith@rush.edu., Klein P; Mid-Atlantic Epilepsy and Sleep Center, Bethesda, MD, USA., Krauss GL; Johns Hopkins University School of Medicine, Baltimore, MD, USA., Rashid S; Epilepsy and Neurology Specialists of San Diego, Encinitas, CA, USA., Seiden LG; Atlanta Neuroscience Institute/MS Center of Atlanta, Atlanta, GA, USA., Stern JM; University of California at Los Angeles, Los Angeles, CA, USA., Rosenfeld WE; Comprehensive Epilepsy Care Center for Children and Adults, St. Louis, MO, USA.
Jazyk: angličtina
Zdroj: Neurology and therapy [Neurol Ther] 2022 Dec; Vol. 11 (4), pp. 1705-1720. Date of Electronic Publication: 2022 Sep 03.
DOI: 10.1007/s40120-022-00400-5
Abstrakt: Introduction: Our objective was to provide expert consensus recommendations to improve treatment tolerability through dose adjustments of concomitant antiseizure medications (ASMs) during addition of cenobamate to existing ASM therapy in adult patients with uncontrolled focal seizures.
Methods: A panel of seven epileptologists experienced in the use of ASMs, including cenobamate, used a modified Delphi process to reach consensus. The panelists discussed tolerability issues with concomitant ASMs during cenobamate titration and practical strategies for dose adjustments that may prevent or mitigate adverse effects. The resulting recommendations consider concomitant ASM dose level and specify proactive (prior to report of an adverse effect) and reactive (in response to report of an adverse effect) dose adjustment suggestions based on concomitant ASM pharmacokinetic and pharmacodynamic interactions with cenobamate. Specific dose adjustment recommendations are provided.
Results: We recommend proactively lowering the dose of clobazam, phenytoin, and phenobarbital due to their known drug-drug interactions with cenobamate, and lacosamide due to a pharmacodynamic interaction with cenobamate, to prevent adverse effects during cenobamate titration. Reactive lowering of a concomitant ASM dose is sufficient for other ASMs at standard dosing owing to quick resolution of adverse effects. For carbamazepine and lamotrigine doses exceeding the upper end of standard dosing (e.g., carbamazepine, greater than 1200 mg/day; lamotrigine, greater than 500 mg/day), we encourage consideration of proactive dose reduction at cenobamate 200 mg/day to prevent potential adverse effects. All dose reductions for adverse effects can be repeated every 2 weeks as dictated by the adverse effects. At cenobamate 200 mg/day, we recommend that patients be evaluated for marked improvement of seizures and further dose reductions be considered to reduce potentially unnecessary polypharmacy.
Conclusion: The primary goal of the recommended dose reductions of concomitant ASMs is to prevent or resolve adverse effects, thereby allowing cenobamate to reach the optimal dose to achieve the maximal potential of improving seizure control.
(© 2022. The Author(s).)
Databáze: MEDLINE
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