Propafenone and Ketoconazole Interaction
Drug interaction information between Propafenone and Ketoconazole.
Propafenone and Ketoconazole have a documented minor interaction in FDA labeling.
FDA drug labeling documents a minor-severity interaction between Propafenone and Ketoconazole. Major interactions are generally avoided, moderate ones may need monitoring or a dose adjustment, and minor ones are usually low-risk. This page shows the documented mechanism and guidance. Label-documented interactions are not a complete safety review, so always confirm your own medications with a pharmacist or doctor. Educational information, not medical advice.
How They Interact
Ketoconazole slows down the liver's ability to break down propafenone, which can cause the drug to build up in your body.
What To Do
Your doctor may need to adjust your dose or monitor you more closely for side effects.
FDA Label Information
(7.6) 7.1 CYP2D6 and CYP3A4 Inhibitors Drugs that inhibit CYP2D6 (such as desipramine, paroxetine, ritonavir, sertraline) and CYP3A4 (such as ketoconazole, ritonavir, saquinavir, erythromycin, grapefruit juice) can be expected to cause increased plasma levels of propafenone.
Propafenone Also Interacts With
- Nirmatrelvir/Ritonavir major
- Amiodarone moderate
- Fluoxetine moderate
- Nebivolol moderate
- Erythromycin minor
Ketoconazole Also Interacts With
- Alfuzosin major
- Dronedarone major
- Ranolazine major
- Saxagliptin major
- Sildenafil major
Frequently Asked Questions
Can I take Propafenone and Ketoconazole together?
This is a minor interaction. Your doctor may need to adjust your dose or monitor you more closely for side effects.
How serious is the interaction between Propafenone and Ketoconazole?
This interaction is classified as "minor" severity by the FDA. Minor interactions are unlikely to cause significant problems but should still be mentioned to your healthcare provider.
Why do Propafenone and Ketoconazole interact?
Ketoconazole slows down the liver's ability to break down propafenone, which can cause the drug to build up in your body.
Understanding the Propafenone and Ketoconazole Interaction
FDA-approved prescribing information for these two drugs flags their combination as a minor-severity interaction. Propafenone belongs to the Class IC Antiarrhythmic class and Ketoconazole belongs to the Azole Antifungal class - two categories that can collide when co-prescribed. The mechanism described in FDA labeling is: Ketoconazole slows down the liver's ability to break down propafenone, which can cause the drug to build up in your body. Severity tiers matter: major flags generally advise avoidance, moderate flags often require monitoring or dose adjustment, and minor flags may only call for awareness.
Context around a specific patient determines real-world impact. Propafenone has 26 total documented interactions on file in this dataset, and Ketoconazole has 113. Each additional medication compounds the interaction surface, which is why pharmacists run full-profile checks rather than evaluating one pair at a time. FDA-derived guidance for this pair is: Your doctor may need to adjust your dose or monitor you more closely for side effects. Timing of doses, renal and hepatic function, age, and other concurrent prescriptions all shape whether a labeled interaction matters clinically.
An interaction flag is not a verdict. A large share of labeled interactions are managed routinely in clinical practice, the fix may be as simple as spacing doses or adding a monitoring test. Others require the prescriber to choose a different medication entirely. This page surfaces FDA-sourced labeling and openFDA data for educational purposes only; it is not medical advice and cannot account for your full clinical picture. Never start, stop, or adjust either Propafenone or Ketoconazole based on a web page, speak with your prescriber or pharmacist before making any change.
Sources: FDA Drug Labels (SPL) via openFDA (2026). This is for informational purposes only and is not medical advice. Always consult your healthcare provider about drug interactions.
Read our methodology - how this data is sourced, computed, and verified.