Drug interactions
Amitriptyline + Primidone
Severity: Major
Amitriptyline and Primidone: 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
Primidone is metabolized to phenobarbital, which induces hepatic enzymes and may reduce amitriptyline levels. Additive sedation is also likely, and tricyclics may lower the seizure threshold.
What this interaction means in plain words
Amitriptyline and Primidone 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.
Amitriptyline belongs to Central Nervous System; Primidone belongs to Central Nervous System.
Why it happens
Enzyme induction (CYP3A4 and CYP2C19) by primidone and its phenobarbital metabolite, plus additive CNS depression.
What to do
Monitor for loss of antidepressant effect, sedation, and seizure control, and adjust amitriptyline dose by response or levels. Reassess dosing if primidone is stopped.
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 Amitriptyline and Primidone, 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 Amitriptyline
- Amitriptyline + Isocarboxazid Contraindicated
- Amitriptyline + Methylene blue Contraindicated
- Amitriptyline + Phenelzine Contraindicated
- Amitriptyline + Pimozide Contraindicated
- Amitriptyline + Procarbazine Contraindicated
- Amitriptyline + Safinamide Contraindicated
Other interactions of Primidone
- Lorlatinib + Primidone Contraindicated
- Lurasidone + Primidone Contraindicated
- Primidone + Ranolazine Contraindicated
- Primidone + Sofosbuvir-velpatasvir-voxilaprevir Contraindicated
- Primidone + Voriconazole Contraindicated
- Abiraterone + Primidone Major
Frequently asked questions
Can I take Amitriptyline with Primidone?
MediHelp rates the interaction as major. Amitriptyline and Primidone 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. Primidone is metabolized to phenobarbital, which induces hepatic enzymes and may reduce amitriptyline levels. Additive sedation is also likely, and tricyclics may lower the seizure threshold.
How serious is the interaction between Amitriptyline and Primidone?
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 for loss of antidepressant effect, sedation, and seizure control, and adjust amitriptyline dose by response or levels. Reassess dosing if primidone is stopped.
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.
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.
