Cannabidiol inhibits phenytoin clearance and can result in clinical changes: Two cases.

PURPOSE: Cannabidiol has well described drug interactions including inhibition of clobazam metabolism. Phenytoin is known to induce metabolism of cannabidiol. Cannabidiol inhibition of phenytoin metabolism is predicted but not well described.

METHODS

We present the cases of two individuals with Lennox Gastaut Syndrome which demonstrate the clinical relevance of cannabidiol inhibition of phenytoin metabolism.

RESULTS

In the first case, the addition of cannabidiol led to increased levels of phenytoin and clobazam which resulted in freedom from previously refractory tonic-clonic seizures. This was sustained for one year. The phenytoin dose was later lowered due to concern for liver function and this led to recurrent seizures despite continued elevation of N-desmethylclobazam levels, suggesting the higher phenytoin was responsible for the seizure control. In the second case, the addition of cannabidiol led to phenytoin toxicity with ataxia and falls. Lowering phenytoin dose led to resolution of these symptoms.

CONCLUSION

Physicians should be aware of the interactions between phenytoin and cannabidiol in the management of epilepsy.