Valproate and Amitriptyline Interaction
Drug interaction information between Valproate and Amitriptyline.
Valproate and Amitriptyline have a documented minor interaction in FDA labeling.
FDA drug labeling documents a minor-severity interaction between Valproate and Amitriptyline. This page displays the available source-record category and label text. The category is not an individual risk estimate or medication-combination direction.
How They Interact
Valproate can slow down how your body breaks down amitriptyline, which may cause the drug to build up in your system.
FDA Label Information
diazepam, ethosuximide, lamotrigine, phenytoin) by inhibiting their metabolism or protein binding displacement ( 7.2 ) • Patients stabilized on rufinamide should begin valproate therapy at a low dose, and titrate to clinically effective dose ( 7.2 ) • Dosage adjustment of amitriptyline/nortriptyline, propofol, warfarin, and zidovudine may be necessary if used concomitantly with valproate ( 7.2 ) • Topiramate: Hyperammonemia and encephalopathy ( 5.9 , 7.3 ) 7.1 Effects of Co-Administered Drugs on Valproate Clearance Drugs that affect the level of expression of hepatic enzymes, particularly...
Valproate Also Interacts With
- Ranitidine major
- Cimetidine major
- Clarithromycin moderate
- Lidocaine Topical moderate
- Risperidone moderate
Amitriptyline Also Interacts With
- Risperidone major
- Sertraline minor
- Fluoxetine minor
- Paroxetine minor
- Disulfiram minor
Frequently Asked Questions
What SPL severity band is on file for Valproate + Amitriptyline?
Compiled FDA labeling labels this pair minor. That is a source-record field, not an individual medication-combination decision.
Which drug in this pair has the larger labeled-interaction portfolio?
Valproate has 41 labeled pairs on file vs Amitriptyline's 21. In the minor band specifically: Valproate has 36 (also Aspirin, Clonazepam, Topiramate, Acetaminophen); Amitriptyline has 20 (also Sertraline, Fluoxetine, Paroxetine, Disulfiram).
What mechanism field is on file for Valproate and Amitriptyline?
Valproate can slow down how your body breaks down amitriptyline, which may cause the drug to build up in your system.
Valproate carries more major-labeled pairs than Amitriptyline
SPL source-record counts only. This page's band is minor · classes on file: Valproate (Anticonvulsant / Mood Stabilizer); Amitriptyline (Tricyclic Antidepressant (TCA)).
Valproate has 2 major-labeled pairs vs Amitriptyline's 1. This page itself is in the minor band, not the major band.
2 major · 3 moderate · 36 minor · 41 total
- Other minor peers for Valproate
- Aspirin
- Clonazepam
- Topiramate
- Acetaminophen
1 major · 0 moderate · 20 minor · 21 total
- Other minor peers for Amitriptyline
- Sertraline
- Fluoxetine
- Paroxetine
- Disulfiram
Sources: FDA Drug Labels (SPL) via openFDA (2026). This is for informational purposes only and is not medical advice. This registry does not provide individual medication-combination directions.
Read our methodology - how this data is sourced, computed, and verified.