Propafenone and Amitriptyline Interaction
Drug interaction information between Propafenone and Amitriptyline.
Propafenone and Amitriptyline have a documented minor interaction in FDA labeling.
FDA drug labeling documents a minor-severity interaction between Propafenone 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
Propafenone can slow down how your body breaks down amitriptyline by blocking a specific enzyme. This can lead to higher levels of amitriptyline in your blood.
FDA Label Information
The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide).
Propafenone Also Interacts With
- Nirmatrelvir/Ritonavir major
- Amiodarone moderate
- Fluoxetine moderate
- Nebivolol moderate
- Ketoconazole minor
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 Propafenone + 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?
Propafenone has 26 labeled pairs on file vs Amitriptyline's 21. In the minor band specifically: Propafenone has 22 (also Ketoconazole, Erythromycin, Desipramine, Cimetidine); Amitriptyline has 20 (also Sertraline, Fluoxetine, Paroxetine, Disulfiram).
What mechanism field is on file for Propafenone and Amitriptyline?
Propafenone can slow down how your body breaks down amitriptyline by blocking a specific enzyme. This can lead to higher levels of amitriptyline in your blood.
Propafenone's labeled portfolio outnumbers Amitriptyline
SPL source-record counts only. This page's band is minor · classes on file: Propafenone (Class IC Antiarrhythmic); Amitriptyline (Tricyclic Antidepressant (TCA)).
1 major · 3 moderate · 22 minor · 26 total
- Other minor peers for Propafenone
- Ketoconazole
- Erythromycin
- Desipramine
- Cimetidine
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.