An interaction between warfarin and cannabidiol, a case report

Grayson, Leslie E.; Vines, Brannon; Nichol, Kate; Szaflarski, Jerzy P.

doi:10.1016/j.ebcr.2017.10.001

Cited by 99 publications

(84 citation statements)

References 10 publications

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“…Most patients taking concomitant clobazam and valproate reduced their doses during the follow‐up, potentially reflecting either the higher incidence of certain AEs observed when these AEDs are administered concomitantly with CBD or the desire of patients to wean from poly‐drug therapy when seizures become better controlled. In addition, a possible interaction between CBD and warfarin necessitating International Normalized Ratio (INR) monitoring in 1 patient from this EAP has been described previously …”

Section: Discussionmentioning

confidence: 93%

Long‐term safety and treatment effects of cannabidiol in children and adults with treatment‐resistant epilepsies: Expanded access program results

et al. 2018

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SummaryObjectiveSince 2014, cannabidiol (CBD) has been administered to patients with treatment‐resistant epilepsies (TREs) in an ongoing expanded‐access program (EAP). We report interim results on the safety and efficacy of CBD in EAP patients treated through December 2016.MethodsTwenty‐five US‐based EAP sites enrolling patients with TRE taking stable doses of antiepileptic drugs (AEDs) at baseline were included. During the 4‐week baseline period, parents/caregivers kept diaries of all countable seizure types. Patients received oral CBD starting at 2‐10 mg/kg/d, titrated to a maximum dose of 25‐50 mg/kg/d. Patient visits were every 2‐4 weeks through 16 weeks and every 2‐12 weeks thereafter. Efficacy endpoints included the percentage change from baseline in median monthly convulsive and total seizure frequency, and percentage of patients with ≥50%, ≥75%, and 100% reductions in seizures vs baseline. Data were analyzed descriptively for the efficacy analysis set and using the last‐observation‐carried‐forward method to account for missing data. Adverse events (AEs) were documented at each visit.ResultsOf 607 patients in the safety dataset, 146 (24%) withdrew; the most common reasons were lack of efficacy (89 [15%]) and AEs (32 [5%]). Mean age was 13 years (range, 0.4‐62). Median number of concomitant AEDs was 3 (range, 0‐10). Median CBD dose was 25 mg/kg/d; median treatment duration was 48 weeks. Add‐on CBD reduced median monthly convulsive seizures by 51% and total seizures by 48% at 12 weeks; reductions were similar through 96 weeks. Proportion of patients with ≥50%, ≥75%, and 100% reductions in convulsive seizures were 52%, 31%, and 11%, respectively, at 12 weeks, with similar rates through 96 weeks. CBD was generally well tolerated; most common AEs were diarrhea (29%) and somnolence (22%).SignificanceResults from this ongoing EAP support previous observational and clinical trial data showing that add‐on CBD may be an efficacious long‐term treatment option for TRE.

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Section: Discussionmentioning

confidence: 93%

Long‐term safety and treatment effects of cannabidiol in children and adults with treatment‐resistant epilepsies: Expanded access program results

et al. 2018

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“…Grayson et al described a 44‐year‐old Caucasian man with Marfan syndrome, mechanical valve replacement and post‐stroke epilepsy. He was prescribed Epidiolex ® , a liquid formulation of cannabidiol (CBD) 5 mg/kg/d, for the management of treatment‐resistant epilepsy.…”

Section: Resultsmentioning

confidence: 99%

“…Both stereoisomers inhibit the vitamin K epoxide reductase complex, but S‐warfarin is about five times more potent than R‐warfarin. S‐warfarin is metabolized via CYP2C9, and R‐warfarin is predominantly metabolized via CYP3A4 . In vitro, the CYP2C9‐mediated 7‐hydroxylation of S‐warfarin is inhibited by various cannabinoids with IC50 values between 2.29 and 4.81 μmol/L .…”

Section: Introductionmentioning

confidence: 99%

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Interaction between warfarin and cannabis

Damkier

Lassen

Christensen

et al. 2018

Basic Clin Pharma Tox

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Delta‐9‐tetrahydrocannabinol (THC), the main psychoactive cannabinoid in cannabis, may inhibit the cytochrome P450 enzyme CYP2C9. Consequently, cannabis use might infer a risk of drug‐drug interaction with substrates for this enzyme, which includes drugs known to have a narrow therapeutic window. In this study, we describe a case report of a 27‐year‐old man treated with warfarin due to mechanical heart valve replacement who presented with elevated international normalized ratio (INR) value (INR = 4.6) following recreational cannabis use. We conducted a review of the available literature, using the PubMed and EMBASE databases while following PRISMA guidelines. Following screening of 85 articles, three eligible articles were identified, including one in vitro study and two case reports. The in vitro study indicated that THC inhibits the CYP2C9‐mediated metabolism of warfarin. One case study reported of a man who on two occasions of increased marijuana use experienced INR values above 10 as well as bleeding. The other case study reported of a patient who initiated treatment with a liquid formulation of cannabidiol for the management of epilepsy, ultimately necessitating a 30% reduction in warfarin dose to maintain therapeutic INR values. The available, although sparse, data suggest that use of cannabinoids increases INR values in patients receiving warfarin. Until further data are available, we suggest patients receiving warfarin be warned against cannabis use.

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“…A case report was released in 2017 describing a 44‐year‐old white man with Marfan syndrome, poststroke epilepsy, and mechanical mitral valve replacement . The patient was diagnosed with a stroke after cardiac surgery at the age of 27, when he was started on warfarin therapy with a goal INR of 2‐3.…”

Section: Resultsmentioning

confidence: 99%

A Review of Cannabis and Interactions With Anticoagulant and Antiplatelet Agents

Gréger

Bates

Mechtler

et al. 2019

The Journal of Clinical Pharma

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Legalization of medical cannabis has occurred in 33 states and the District of Columbia, and recreational use has increased exponentially since 2013. As a result, it is important to understand how cannabis interacts with other drugs and has potential risks for patients on concomitant medications. Components of medical cannabis can inhibit or compete for several cytochrome P450 (CYP) hepatic isoenzymes, UDP‐glucuronosyltransferases, and P‐glycoprotein. These enzymes and transporters are involved in the metabolism and absorption of numerous medications, including anticoagulants (ACs) and antiplatelet agents (APs), potentially causing harmful drug‐drug interactions. ACs and/or APs are often prescribed to high‐risk patients with cardiac conditions, a history of myocardial infarction, or stroke. Cannabis may cause these medications to be less efficacious and put patients at risk for recurrent cardiovascular and cerebrovascular events. Several case reports show cannabis may inhibit the metabolism of warfarin because of CYP2C9 interactions, resulting in increased plasma concentrations, increased international normalized ratio, and risk of bleeding. Cannabidiol inhibits CYP2C19, an isoenzyme responsible for the transformation of clopidogrel to its active thiol metabolite. This interaction could lead to subtherapeutic levels of active metabolite and possibly increased stroke risk. Within this review, a total of 665 articles were screened from PubMed and EMBASE. Four case reports, 1 in vitro study, and 1 pharmacokinetic article were found to be of relevance. This review serves to examine reported and potential cannabis interactions with APs/ACs to help inform patients and health care providers of possible risks and knowledge gaps.

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An interaction between warfarin and cannabidiol, a case report

Abstract: HighlightsAn interaction between warfarin and cannabidiol is describedThe mechanisms of cannabidiol and warfarin metabolism are reviewedMechanism of the interaction is proposedINR should be monitored in patients when cannabinoids are introduced

Cited by 99 publications

References 10 publications

Long‐term safety and treatment effects of cannabidiol in children and adults with treatment‐resistant epilepsies: Expanded access program results

Long‐term safety and treatment effects of cannabidiol in children and adults with treatment‐resistant epilepsies: Expanded access program results

Interaction between warfarin and cannabis

A Review of Cannabis and Interactions With Anticoagulant and Antiplatelet Agents

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