Drug interactions
Phenytoin + Trazodone
Severity: Moderate
Phenytoin and Trazodone: moderate 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
Case reports have described raised phenytoin concentrations after trazodone was added, though the data are sparse. Phenytoin has a narrow therapeutic range, so toxicity such as ataxia or nystagmus could occur if levels rise. Phenytoin may also lower trazodone exposure through enzyme induction.
What this interaction means in plain words
Phenytoin and Trazodone can affect each other. The combination is often manageable, but it may need a change of dose, a change of timing, or extra checks while both are taken.
Phenytoin belongs to Central Nervous System; Trazodone belongs to Central Nervous System.
Why it happens
The mechanism is not established; possible altered phenytoin metabolism, and phenytoin may induce CYP3A4 metabolism of trazodone.
What to do
Check phenytoin concentrations after starting or stopping trazodone and watch for signs of toxicity. Review trazodone response, as dose increases may be needed.
What to ask your pharmacist
- Should I take them at different times of day?
- Does the dose of either medicine need to change?
- Is there anything I should avoid, such as alcohol or certain foods, while on both?
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Other interactions of Trazodone
- Arsenic trioxide + Trazodone Contraindicated
- Ibutilide + Trazodone Contraindicated
- Isocarboxazid + Trazodone Contraindicated
- Levoketoconazole + Trazodone Contraindicated
- Methylene blue + Trazodone Contraindicated
- Phenelzine + Trazodone Contraindicated
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 Phenytoin with Trazodone?
MediHelp rates the interaction as moderate. Phenytoin and Trazodone can affect each other. The combination is often manageable, but it may need a change of dose, a change of timing, or extra checks while both are taken. Case reports have described raised phenytoin concentrations after trazodone was added, though the data are sparse. Phenytoin has a narrow therapeutic range, so toxicity such as ataxia or nystagmus could occur if levels rise. Phenytoin may also lower trazodone exposure through enzyme induction.
How serious is the interaction between Phenytoin and Trazodone?
MediHelp rates it moderate, on a four-level scale (minor, moderate, major, contraindicated) based on published labels and references. What to do, in brief: Check phenytoin concentrations after starting or stopping trazodone and watch for signs of toxicity. Review trazodone response, as dose increases may be needed.
What other medicines interact with Trazodone?
MediHelp also lists interactions of Trazodone with, for example, Arsenic trioxide, Ibutilide, Isocarboxazid. The full list is on the Trazodone page.
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