Drug interactions
Amitriptyline + Phenytoin
Severity: Moderate
Amitriptyline and Phenytoin: 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
Phenytoin induces hepatic enzymes and can lower amitriptyline concentrations, reducing antidepressant effect. Tricyclics may also lower the seizure threshold, and in some cases alter phenytoin levels, so seizure control can be affected.
What this interaction means in plain words
Amitriptyline and Phenytoin 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.
Amitriptyline belongs to Central Nervous System; Phenytoin belongs to Central Nervous System.
Why it happens
Phenytoin induces CYP enzymes (including CYP3A4 and CYP2C19) that metabolize amitriptyline, while tricyclics have proconvulsant effects and may affect phenytoin metabolism.
What to do
Monitor depressive symptoms and increase the amitriptyline dose if needed. Check serum phenytoin concentrations when starting or changing the tricyclic and watch for seizure breakthrough.
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 Amitriptyline
- Amitriptyline + Isocarboxazid Contraindicated
- Amitriptyline + Methylene blue Contraindicated
- Amitriptyline + Phenelzine Contraindicated
- Amitriptyline + Pimozide Contraindicated
- Amitriptyline + Procarbazine Contraindicated
- Amitriptyline + Safinamide 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 Amitriptyline with Phenytoin?
MediHelp rates the interaction as moderate. Amitriptyline and Phenytoin 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 induces hepatic enzymes and can lower amitriptyline concentrations, reducing antidepressant effect. Tricyclics may also lower the seizure threshold, and in some cases alter phenytoin levels, so seizure control can be affected.
How serious is the interaction between Amitriptyline and Phenytoin?
MediHelp rates it moderate, on a four-level scale (minor, moderate, major, contraindicated) based on published labels and references. What to do, in brief: Monitor depressive symptoms and increase the amitriptyline dose if needed. Check serum phenytoin concentrations when starting or changing the tricyclic and watch for seizure breakthrough.
What other medicines interact with Amitriptyline?
MediHelp also lists interactions of Amitriptyline with, for example, Isocarboxazid, Methylene blue, Phenelzine. The full list is on the Amitriptyline page.
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