Fentanyl and Ketoconazole Interaction
Drug interaction information between Fentanyl and Ketoconazole.
Fentanyl and Ketoconazole have a documented minor interaction in FDA labeling.
FDA drug labeling documents a minor-severity interaction between Fentanyl 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
This combination can change how your body processes fentanyl, which may lower the amount of medicine in your blood. This can make the pain relief less effective or cause withdrawal symptoms.
What To Do
Your doctor may need to adjust your fentanyl dose and watch you closely to ensure the medicine is still working for your pain.
FDA Label Information
ketoconazole), protease inhibitors (e.g., ritonavir), grapefruit juice CYP3A4 Inducers Clinical Impact: The concomitant use of Fentanyl Citrate Injection and CYP3A4 inducers can decrease the plasma concentration of fentanyl [see Clinical Pharmacology ( 12.3 )] , resulting in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence to fentanyl [see Warnings and Precautions ( 5.4 )] .
Fentanyl Also Interacts With
- Itraconazole moderate
- Tranylcypromine moderate
- Tramadol minor
- Cyclobenzaprine minor
- Diazepam minor
Ketoconazole Also Interacts With
- Alfuzosin major
- Dronedarone major
- Ranolazine major
- Saxagliptin major
- Sildenafil major
Frequently Asked Questions
Can I take Fentanyl and Ketoconazole together?
This is a minor interaction. Your doctor may need to adjust your fentanyl dose and watch you closely to ensure the medicine is still working for your pain.
How serious is the interaction between Fentanyl 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 Fentanyl and Ketoconazole interact?
This combination can change how your body processes fentanyl, which may lower the amount of medicine in your blood. This can make the pain relief less effective or cause withdrawal symptoms.
Understanding the Fentanyl and Ketoconazole Interaction
FDA-approved prescribing information for these two drugs flags their combination as a minor-severity interaction. Fentanyl belongs to the Opioid Analgesic class and Ketoconazole belongs to the Azole Antifungal class - two categories that can collide when co-prescribed. The mechanism described in FDA labeling is: This combination can change how your body processes fentanyl, which may lower the amount of medicine in your blood. 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. Fentanyl has 28 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 fentanyl dose and watch you closely to ensure the medicine is still working for your pain. 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 Fentanyl 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.