Cannabidiol May Negatively Interact With Antiepileptic Drugs
Cannabidiol, a compound of cannabis that is being investigated as a potential treatment for epilepsy, may negatively interact with commonly used antiepileptic drugs (AEDs), new research suggests.
Analysis from an ongoing, open-label compassionate-use study included 42 children and 39 adults given the cannabidiol (CBD) Epidiolex (GW Pharmaceuticals, plc) to augment their epilepsy treatment. Results from the full group showed an increasing dose of CBD was associated with significant increases in serum levels of rufinamide, topiramate, and N-desmethylclobazam and a significant decrease in clobazam.
The adult-only subgroup also showed a significant association between increasing CBD dose and increased zonisamide and eslicarbazepine serum levels.
All these serum-level changes were considered to be within the accepted therapeutic range except for N-desmethylclobazam/clobazam.
However, increasing CBD dosing was linked to changes on liver function tests for the full study population receiving concomitant valproate.
Lead author Tyler E. Gaston, MD, assistant professor of neurology at the University of Alabama at Birmingham Epilepsy Center, told Medscape Medical News that the results highlight the importance of monitoring AED levels, as well as liver tests, when treating with CBD.
Dr Tyler E. Gaston
Also, if Epidiolex goes for US Food and Drug Administration approval, “this is something that clinicians will need to know about when counseling their patients,” said Dr Gaston.
The findings were published online August 6 in Epilepsia.
As reported by Medscape Medical News, previous research suggests CBD can reduce seizures in a variety of epilepsy disorders, including Dravet syndrome and Lennox-Gastaut syndrome.
However, “to date, there are few data on CBD’s interactions with other AEDs,” write the investigators.
The University of Alabama at Birmingham’s prospective, compassionate-use study was created to assess CBD’s safety and potential as an add-on therapy for treatment-resistant epilepsy. And it includes frequent monitoring of serum AED levels in case of any drug–drug interactions.
“Given what is known about CBD’s mechanism of action and metabolism, it was suspected that other AEDs with metabolism hinging on similar enzymes would be affected,” the researchers write.
All participants began taking 5 mg/kg per day of CBD. They were instructed to split it into two doses — one in the morning and one in the evening — and to take it along with their other AEDs.
The patients attended the clinic every 2 weeks, where CBD dose adjustments were made in 5 mg/kg per day increments, based on response and tolerability, up to a maximum of 50 mg/kg per day.
At each visit, patients were also weighed and underwent neurologic examinations and laboratory testing. Each patient’s “seizure diary,” which included possible adverse effects, was also reviewed. Aspartate aminotransferase and alanine aminotransferase levels were compared with liver function test findings at baseline in those taking concomitant valproate.
For the current analysis, the investigators examined first-year data for 39 adult participants (51% women; mean age, 29.1 years) and 42 pediatric participants (48% girls; mean age, 10.4 years). The mean age at seizure onset was 7.2 and 2.4 years, respectively, and the mean number of AEDs taken at enrollment was 3.2 and 3.0, respectively.
In addition, the most common type of seizures for the adults was partial only (n = 26), followed by generalized only (n=8). For the children, generalized-only seizures were the most common (n = 28), followed by partial only (n=8).
Results from the full group showed that increasing CBD dose was significantly associated with increased levels of the following:
N-desmethylclobazam (the active metabolite of clobazam, P
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Cite this: Cannabidiol May Negatively Interact With Antiepileptic Drugs – Medscape – Aug 18, 2017.Cannabidiol can change serum levels of several commonly used antiepileptic drugs in both adult and pediatric patients with epilepsy, new research suggests.
Cannabidiol Interacts with Multiple Epilepsy Drugs
— Four agents in addition to clobazam identified in open-label study
by Kristina Fiore, Associate Editor, MedPage Today December 5, 2016
HOUSTON — Cannabidiol is likely to interact with more anti-epileptic agents than just clobazam, researchers reported here.
In an open-label study of 81 adult and pediatric patients, the cannabis derivative also showed drug-drug interactions with topiramate and rufinamide, Tyler Gaston, MD, of the University of Alabama at Birmingham, and colleagues reported at the American Epilepsy Society meeting here.
Cannabidiol appeared to interact with zonisamide and eslicarbazepine as well, but only in adults, the researchers reported.
“With marijuana, the general idea is that it’s a safe product, and while that may be true, I think there are some caveats to that and I think that physicians need to be monitoring and managing this,” Gaston told MedPage Today.
The cannabidiol-clobazam interaction has been well established, particularly with the active metabolite N-desmethylclobazam, the researchers said. However, there are no published human data on cannabidiol’s potential interactions with other anti-epileptic drugs.
So Gaston and colleagues monitored patients who were enrolled in a state-based compassionate use study of cannabidiol for those who were refractory to at least four other anti-epileptic drugs. Over a year of monitoring, they collected data on 81 patients: 39 adults and 42 children.
Cannabidiol dosing was weight-based, starting at at 5 mg/kg per day, split into twice-daily dosing.Four agents in addition to clobazam identified in open-label study ]]>