Drug interactions
Cannabidiol + Phenytoin
Severity: Major
Cannabidiol and Phenytoin: major interaction.
Last updated
For healthcare professionals — reference only. This page is a brief summary, not medical advice and not a substitute for official labeling or clinical judgement. Always verify before prescribing or dispensing.
Summary
The interaction runs in both directions. Phenytoin may lower cannabidiol exposure through CYP3A4 induction, reducing seizure control. Cannabidiol may raise phenytoin concentrations through inhibition of CYP2C19 and CYP2C9, which can lead to phenytoin toxicity given its narrow therapeutic index.
What this interaction means in plain words
Cannabidiol and Phenytoin can interact in a way that may be serious. Using them together is sometimes necessary, but it needs a deliberate decision by the prescriber, a plan for monitoring, and clear advice on the warning signs to watch for.
Cannabidiol belongs to Central Nervous System; Phenytoin belongs to Central Nervous System.
Why it happens
Phenytoin induces CYP3A4 and CYP2C19 metabolism of cannabidiol, while cannabidiol inhibits CYP2C19 and CYP2C9 metabolism of phenytoin.
What to do
Monitor phenytoin serum levels and signs of toxicity such as nystagmus, ataxia and sedation when cannabidiol is started or changed, and reduce the phenytoin dose as needed. Consider raising the cannabidiol dose according to response and tolerability.
What to ask your pharmacist
- Does the benefit of taking both outweigh the risk in my case?
- Do I need any blood test, ECG or other check while on both?
- What early warning signs should I watch for, and what should I do if they appear?
Pro+ members
Unlock the full page
Create an account and start a Pro+ trial to unlock the full management advice for Cannabidiol and Phenytoin, the additional notes, the evidence detail and the whole-prescription interaction checker.
- Full clinical management advice
- Additional notes
- Evidence detail
- Interaction checker for a whole prescription
Try Pro+ free for 14 days on the web. No card needed.
Other interactions of Phenytoin
- Artemether / lumefantrine + Phenytoin Contraindicated
- Bictegravir + Phenytoin Contraindicated
- Cabotegravir + Phenytoin Contraindicated
- Doravirine + Phenytoin Contraindicated
- Elbasvir / grazoprevir + Phenytoin Contraindicated
- Elvitegravir / cobicistat / emtricitabine / tenofovir df + Phenytoin Contraindicated
Other interactions of Cannabidiol
- Cannabidiol + Sodium valproate Major
- Cannabidiol + Tacrolimus Major
- Abiraterone + Cannabidiol Moderate
- Alogliptin-pioglitazone + Cannabidiol Moderate
- Amiodarone + Cannabidiol Moderate
- Amobarbital + Cannabidiol Moderate
Frequently asked questions
Can I take Cannabidiol with Phenytoin?
MediHelp rates the interaction as major. Cannabidiol and Phenytoin can interact in a way that may be serious. Using them together is sometimes necessary, but it needs a deliberate decision by the prescriber, a plan for monitoring, and clear advice on the warning signs to watch for. The interaction runs in both directions. Phenytoin may lower cannabidiol exposure through CYP3A4 induction, reducing seizure control. Cannabidiol may raise phenytoin concentrations through inhibition of CYP2C19 and CYP2C9, which can lead to phenytoin toxicity given its narrow therapeutic index.
How serious is the interaction between Cannabidiol and Phenytoin?
MediHelp rates it major, on a four-level scale (minor, moderate, major, contraindicated) based on published labels and references. What to do, in brief: Monitor phenytoin serum levels and signs of toxicity such as nystagmus, ataxia and sedation when cannabidiol is started or changed, and reduce the phenytoin dose as needed. Consider raising the cannabidiol dose according to response and tolerability.
What other medicines interact with Phenytoin?
MediHelp also lists interactions of Phenytoin with, for example, Artemether / lumefantrine, Bictegravir, Cabotegravir. The full list is on the Phenytoin page.
Full monographs, dosing and an interaction checker in the MediHelp app
Open the complete reference, check multi-drug interactions and use dosing tools in the MediHelp app.
