Lacosamide and sodium channel‐blocking antiepileptic drug cross‐titration against levetiracetam background therapy

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Excerpt

Given the large number of available antiepileptic drugs (AEDs) and the even larger number of possible combinations, systematic evaluation of optimal AED combinations is not feasible.1
It has been proposed that combination therapy should include selection of drugs with low potential for drug‐drug interactions (DDIs) and for amplification of adverse effects, while minimizing total drug load.2 Combining AEDs based on their mechanism of action can also provide a rational approach to the challenge.1 While the potential for enhanced neurotoxicity when combining two sodium channel‐blocking AEDs was observed over 40 years ago, evidence for enhanced efficacy with specific combinations remains inconsistent.4
While traditional sodium channel blockers (SCBs) such as phenytoin, carbamazepine and lamotrigine act by inhibiting fast inactivation of the channels, lacosamide (LCM) selectively enhances slow inactivation.7 Post hoc analyses of data pooled from double‐blind, placebo‐controlled trials suggested that the combination of LCM with a non‐SCB might be associated with better tolerability than with a SCB.9 A retrospective study also highlighted cases of patients who did not tolerate LCM 200‐350 mg/day without concurrent reduction of carbamazepine or oxcarbazepine.10 Levetiracetam (LEV) is a non‐SCB AED; therefore, based on their differing mechanisms of action and low potential for DDIs, the combination of LCM and LEV may provide additional therapeutic benefit.
The objective of the trial reported here was to evaluate prospectively the effectiveness of LCM when added to LEV, with cross‐titration (discontinuation) of the concomitant SCB among patients with focal epilepsy.
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