CBD führt zu klinisch relevanter Arzneimittelinteraktion mit Clobazam (stark erhöhte Norclobazam-Spiegel), ermöglicht aber bei 70% der Patienten eine >50%ige Anfallsreduktion.
Zusammenfassung
n=13 Kinder mit therapierefraktärer Epilepsie unter Clobazam (CLB) + CBD (IND-Studie): 9 von 13 Patienten (70%) zeigten >50% Anfallsreduktion. CLB-Spiegel stiegen um 60±80% (95%-KI –2 bis 91%) bei 4 Wochen; N-Desmethylclobazam (nCLB) um 500±300% (95%-KI +90 bis +610%). CLB-Dosis bei 10 von 13 Patienten (77%) reduziert; Nebenwirkungen bei 10 von 13 (77%), durch CLB-Dosisreduktion behoben.
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PopulationKinder mit refraktärer Epilepsie unter gleichzeitiger Clobazam-Therapie, n=13
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InterventionCannabidiol (CBD) als adjuvante Therapie (erweiterter Zugang, IND 119876), Dosis nicht spezifiziert, oral, über mind. 8 Wochen
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OutcomeMittlere Anstieg der nCLB-Spiegel um 500 ± 300% (95%-KI +90–610%) nach 4 Wochen; 9/13 Patienten (70%) zeigten >50% Anfallsreduktion; Nebenwirkungen bei 77%, durch CLB-Dosisreduktion beherrschbar
Vertrauen in die Evidenz
Sehr niedrigNiedrigModeratHoch
Moderat
Dritte von vier GRADE-Stufen, die Effektschätzung ist wahrscheinlich verlässlich.
<h4>Objective</h4>Under an expanded access investigational new drug (IND) trial, cannabidiol (CBD) is being studied as a possible adjuvant treatment of refractory epilepsy in children. Of the 25 subjects in the trial, 13 were being treated with clobazam (CLB). Because CLB and CBD are both metabolized in the cytochrome P450 (CYP) pathway, we predicted a drug-drug interaction, which we evaluate in this article.<h4>Methods</h4>Thirteen subjects with refractory epilepsy concomitantly taking CLB and CBD under IND 119876 were included in this study. Demographic information was collected for each subject including age, sex, and etiology of seizures, as well as concomitant antiepileptic drugs (AEDs). CLB, N-desmethylclobazam (norclobazam; nCLB), and CBD levels were measured over the course of CBD treatment. CLB doses were recorded at baseline and at weeks 4 and 8 of CBD treatment. Side effects were monitored.<h4>Results</h4>We report elevated CLB and nCLB levels in these subjects. The mean (± standard deviation [SD]) increase in CLB levels was 60 ± 80% (95% confidence interval (CI) [-2-91%] at 4 weeks); the mean increase in nCLB levels was 500 ± 300% (95% CI [+90-610%] at 4 weeks). Nine of 13 subjects had a >50% decrease in seizures, corresponding to a responder rate of 70%. The increased CLB and nCLB levels and decreases in seizure frequency occurred even though, over the course of CBD treatment, CLB doses were reduced for 10 (77%) of the 13 subjects. Side effects were reported in 10 (77%) of the 13 subjects, but were alleviated with CLB dose reduction.<h4>Significance</h4>Monitoring of CLB and nCLB levels is necessary for clinical care of patients concomitantly on CLB and CBD. Nonetheless, CBD is a safe and effective treatment of refractory epilepsy in patients receiving CLB treatment.