Effects of cannabidiol on brivaracetam plasma levels

Klotz, Kerstin Alexandra; Hirsch, M.; Heers, Marcel; Schulze‐Bonhage, Andreas; Jacobs, Julia

doi:10.1111/epi.16071

Cited by 48 publications

(20 citation statements)

References 17 publications

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“…The only patient with no increase in D-CLB level was also on primidone, a potent inducer of Cytochrome P450 (CYP) enzymes, counteracting the CYP-enzyme inhibiting effect of CBD. However, we also found interaction with other AED, such as BRV that is described in detail elsewhere, and potential interaction with other comedications as omeprazole (23). Cannabidiol is known for its high interaction potential but further pharmacokinetic studies are needed to understand clinically relevant interactions with AED and other drugs in mono-and polytherapy (24).…”

Section: Discussionsupporting

confidence: 58%

Efficacy and Tolerance of Synthetic Cannabidiol for Treatment of Drug Resistant Epilepsy

et al. 2019

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Objective: Controlled and open label trials have demonstrated efficacy of cannabidiol for certain epileptic encephalopathies. However, plant derived cannabidiol products have been used almost exclusively. Efficacy of synthetically derived cannabidiol has not been studied before. The objective of this study was to evaluate tolerability and efficacy of synthetic cannabidiol in patients with pharmacoresistant epilepsy. Methods: In this prospective, open-label study (DRKS00013177), patients with pharmacoresistant epilepsy received synthetic cannabidiol in addition to their previously stable anticonvulsive treatment. Starting dose was 5 mg/kg/day, up-titrated to a maximum of 50 mg/kg/day. Primary efficacy endpoint was monthly frequency of motor seizures at 3 months. Results: Between April 2017 and May 2019, 35 patients were enrolled in the study. Mean age was 19.7 years (SD 14.6). Median motor seizure frequency decreased from 21.8 (IQR 7.5-52.5) seizures per month at baseline to 8.5 (IQR 3.7-28.3, p < 0.001) at 3 months, effect not influenced by AED changes and drop-outs. Adjusted percentage reduction was 40.0% (IQR 18.2-58.5). Adverse events (AE) were reported in 25 patients (71.4%), most frequently somnolence (40%), diarrhea (34.3), and loss of appetite (20%). Two patients (5.7%) discontinued treatment due to AE. Median (range) of treatment duration was 321 days (range 36-824). With ongoing treatment up to date in 21 patients (60%). Conclusion: Efficacy and tolerance in our study of synthetic CBD treatment in pharmacoresistant epilepsy is similar to open label studies using plant derived CBD. Regarding economic and ecological aspects, synthetic cannabidiol might be a reasonable alternative to plant derived cannabidiol.

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Section: Discussionsupporting

confidence: 58%

Efficacy and Tolerance of Synthetic Cannabidiol for Treatment of Drug Resistant Epilepsy

et al. 2019

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“…It was suggested that the inhibition of CYP2C19 by cannabidiol might be responsible for this interaction. 57 No relevant interactions have been observed between 100 mg BRV per day and combined oral contraceptives (30 µg ethinyl estradiol, 150 µg levonorgestrel). 58 Usually, supratherapeutic doses of 400 mg BRV per day resulted in a 27% reduction pf plasma levels of ethinyl estradiol and a 23% reduction in levonorgestrel levels.…”

Section: Pharmacokinetics and Pharmacodynamics Of Brivaracetammentioning

confidence: 99%

Levetiracetam and brivaracetam: a review of evidence from clinical trials and clinical experience

Steinhoff

Staack

2019

Ther Adv Neurol Disord

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Until the early 1990s, a limited number of antiepileptic drugs (AEDs) were available. Since then, a large variety of new AEDs have been developed and introduced, several of them offering new modes of action. One of these new AED families is described and reviewed in this article. Levetiracetam (LEV) and brivaracetam (BRV) are pyrrolidone derivate compounds binding at the presynaptic SV2A receptor site and are thus representative of AEDs with a unique mode of action. LEV was extensively investigated in randomized controlled trials and has a very promising efficacy both in focal and generalized epilepsies. Its pharmacokinetic profile is favorable and LEV does not undergo clinically relevant interactions. Adverse reactions comprise mainly asthenia, somnolence, and behavioral symptoms. It has now been established as a first-line antiepileptic drug. BRV has been recently introduced as an adjunct antiepileptic drug in focal epilepsy with a similarly promising pharmacokinetic profile and possibly increased tolerability concerning psychiatric adverse events. This review summarizes the essential preclinical and clinical data of LEV and BRV that is currently available and includes the experiences at a large tertiary referral epilepsy center.

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“…Cannabidiol is a potent inhibitor of CYP2C19, CYP2D6, and CYP2C9, which leads to an increase in the level of several antiepileptic drugs, with the most significant effect being on clobazam and its metabolite N-desmethylclobazam, and a less prominent effect on topiramate, eslicarbazepine, zonisamide, rufinamide, and brivaracetam. [48][49][50] Abnormal elevation in liver enzymes (transaminases) can occur with concomitant use of valproate and CBD without significant changes in the valproate levels, suggesting a pharmacodynamic rather than a pharmacokinetic interaction. 32…”

Section: Cannabidiol Interactionsmentioning

confidence: 99%

Medical Cannabis for Intractable Epilepsy in Childhood: A Review

Ben‐Zeev

2020

Rambam Maimonides Med J

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In recent years, cannabis has been gaining increasing interest in both the medical research and clinical fields, with regard to its therapeutic effects in various disorders. One of the major fields of interest is its role as an anticonvulsant for refractory epilepsy, especially in the pediatric population. This paper presents and discusses the current accumulated knowledge regarding artisanal cannabis and Epidiolex®, a United States Food and Drug Administration (FDA)-approved pure cannabidiol (CBD), in epilepsy management in pediatrics, by reviewing the literature and raising debate regarding further research directions.

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Effects of cannabidiol on brivaracetam plasma levels

Cited by 48 publications

References 17 publications

Efficacy and Tolerance of Synthetic Cannabidiol for Treatment of Drug Resistant Epilepsy

Efficacy and Tolerance of Synthetic Cannabidiol for Treatment of Drug Resistant Epilepsy

Levetiracetam and brivaracetam: a review of evidence from clinical trials and clinical experience

Medical Cannabis for Intractable Epilepsy in Childhood: A Review

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