Drug interactions
Amitriptyline + Fosphenytoin
Severity: Moderate
Amitriptyline and Fosphenytoin: 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, the active form of fosphenytoin, induces hepatic enzymes and may lower amitriptyline concentrations, reducing antidepressant effect. Tricyclics may also lower the seizure threshold, which could oppose anticonvulsant control.
What this interaction means in plain words
Amitriptyline and Fosphenytoin 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; Fosphenytoin belongs to Central Nervous System.
Why it happens
Phenytoin induction of CYP enzymes including CYP3A4 and CYP2C19, and possibly P-gp, increases amitriptyline clearance.
What to do
Monitor antidepressant response and seizure control, adjusting the amitriptyline dose upward if needed. Monitor phenytoin levels if the regimen changes.
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 Fosphenytoin
- Dronedarone + Fosphenytoin Contraindicated
- Fosphenytoin + Ledipasvir-sofosbuvir Contraindicated
- Fosphenytoin + Lorlatinib Contraindicated
- Fosphenytoin + Lurasidone Contraindicated
- Fosphenytoin + Ranolazine Contraindicated
- Fosphenytoin + Sofosbuvir-velpatasvir-voxilaprevir Contraindicated
Frequently asked questions
Can I take Amitriptyline with Fosphenytoin?
MediHelp rates the interaction as moderate. Amitriptyline and Fosphenytoin 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, the active form of fosphenytoin, induces hepatic enzymes and may lower amitriptyline concentrations, reducing antidepressant effect. Tricyclics may also lower the seizure threshold, which could oppose anticonvulsant control.
How serious is the interaction between Amitriptyline and Fosphenytoin?
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 antidepressant response and seizure control, adjusting the amitriptyline dose upward if needed. Monitor phenytoin levels if the regimen changes.
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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