Drug-drug interaction between clobazam and cannabidiol in children with refractory epilepsy

Can cannabinoids interact with seizure medications?

Yes. JR

Medical marijuana?

Drug-drug interaction between clobazam and cannabidiol
in children with refractory epilepsy.

Authors:

Geffrey, Alexandra L.1
Pollack, Sarah F.1
Bruno, Patricia L.1
Thiele, Elizabeth A.1

Source:

Epilepsia (Series 4). Aug2015, Vol. 56 Issue 8, p1246-1251. 6p.

Document Type:

Article

Subject Terms:

*EPILEPSY in children
*CANNABINOIDS
*BENZODIAZEPINES
*DRUG interactions
*COMBINATION drug therapy
*CYTOCHROME P-450
*SPASMS
TREATMENT
THERAPEUTIC use

Author-Supplied Keywords:

Antiepileptic drugs
Cannabis
Cytochrome P450 pathway
Norclobazam
Treatment-resistant epilepsy

Abstract:

Objective 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. Methods 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. Results We report elevated CLB and n CLB 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. Significance Monitoring of CLB and n CLB 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. [ABSTRACT FROM AUTHOR]

 

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Author Affiliations:

1Massachusetts General Hospital

ISSN:

0013-9580

DOI:

10.1111/epi.13060

Accession Number:

108673345

Publisher Logo: