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Mammalian Target of Rapamycin Inhibitor Levels Decrease Under Cenobamate Treatment.

Lena-Luise Becker1, Karen Agricola2, David M Ritter2

  • 1Institute of Cell Biology and Neurobiology, Department of Pediatric Neurology, Center for Chronically Sick Children, Charité-Universitätsmedizin Berlin, Berlin, Germany.

Pediatric Neurology
|September 21, 2024
PubMed
Summary
This summary is machine-generated.

Cenobamate use in Tuberous Sclerosis Complex (TSC) patients on mammalian target of rapamycin inhibitors (mTORi) led to a significant decrease in everolimus levels. Monitoring mTORi levels is recommended when co-administering with cenobamate.

Keywords:
CenobamateEverolimusSirolimusTuberous sclerosis complexmTOR inhibitor

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Area of Science:

  • Pharmacology
  • Neurology
  • Oncology

Background:

  • Everolimus is approved for drug-resistant epilepsy in Tuberous Sclerosis Complex (TSC).
  • Cenobamate, a newer anti-seizure medication, is increasingly used in TSC patients.
  • Potential drug-drug interactions between cenobamate and mammalian target of rapamycin inhibitors (mTORi) are not well-studied.

Purpose of the Study:

  • To evaluate the impact of cenobamate on serum drug levels of mTORi in patients with TSC.
  • To investigate potential drug-drug interactions between cenobamate and mTORi.

Main Methods:

  • Retrospective analysis of 20 patients with TSC.
  • Comparison of mTORi (everolimus or sirolimus) drug levels before and after cenobamate initiation.

Main Results:

  • Everolimus levels significantly decreased (P=0.01221) after cenobamate initiation.
  • Sirolimus levels did not show a significant change (P=0.3828).
  • Cenobamate showed varying efficacy in seizure control, with 10% achieving seizure freedom.

Conclusions:

  • Cenobamate initiation leads to decreased everolimus levels in TSC patients, likely due to CYP3A4 induction.
  • Monitoring of mTORi serum levels and dose adjustment is recommended when co-administered with cenobamate.