Drug interactions
Cimetidine + Phenytoin
Severity: Major
Cimetidine and Phenytoin: major interaction.
Last updated Sources: US FDA label
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
Cimetidine can raise serum phenytoin concentrations, sometimes into the toxic range. Because phenytoin has saturable kinetics and a narrow therapeutic window, nystagmus, ataxia and confusion may result.
What this interaction means in plain words
Cimetidine 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.
Cimetidine belongs to Gastrointestinal Tract; Phenytoin belongs to Central Nervous System.
Why it happens
Cimetidine inhibits hepatic CYP2C9 and CYP2C19 metabolism of phenytoin.
What to do
Monitor phenytoin serum levels and signs of toxicity when starting or stopping cimetidine, and adjust the dose accordingly. Prefer famotidine or a proton pump inhibitor where possible.
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?
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References
Other interactions of Cimetidine
- Cimetidine + Dofetilide Contraindicated
- Cimetidine + Fezolinetant Contraindicated
- Alfentanil + Cimetidine Major
- Atazanavir + Cimetidine Major
- Carmustine + Cimetidine Major
- Cimetidine + Citalopram Major
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
Frequently asked questions
Can I take Cimetidine with Phenytoin?
MediHelp rates the interaction as major. Cimetidine 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. Cimetidine can raise serum phenytoin concentrations, sometimes into the toxic range. Because phenytoin has saturable kinetics and a narrow therapeutic window, nystagmus, ataxia and confusion may result.
How serious is the interaction between Cimetidine 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 when starting or stopping cimetidine, and adjust the dose accordingly. Prefer famotidine or a proton pump inhibitor where possible.
What other medicines interact with Cimetidine?
MediHelp also lists interactions of Cimetidine with, for example, Dofetilide, Fezolinetant, Alfentanil. The full list is on the Cimetidine page.
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