Zaleplon and Ketoconazole Interaction
Drug interaction information between Zaleplon and Ketoconazole.
Zaleplon and Ketoconazole have a documented minor interaction in FDA labeling.
FDA drug labeling documents a minor-severity interaction between Zaleplon 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 process zaleplon, which can lead to higher levels of the sleep medicine in your blood.
What To Do
Your doctor may need to lower your dose of zaleplon. Watch for increased sleepiness or dizziness while taking both medications.
FDA Label Information
Other strong selective CYP3A4 inhibitors such as ketoconazole can also be expected to increase the exposure of zaleplon.
Zaleplon Also Interacts With
- Ibuprofen minor
- Venlafaxine minor
- Paroxetine minor
- Warfarin minor
- Carbamazepine minor
Ketoconazole Also Interacts With
- Alfuzosin major
- Dronedarone major
- Ranolazine major
- Saxagliptin major
- Sildenafil major
Frequently Asked Questions
Can I take Zaleplon and Ketoconazole together?
This is a minor interaction. Your doctor may need to lower your dose of zaleplon. Watch for increased sleepiness or dizziness while taking both medications.
How serious is the interaction between Zaleplon 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 Zaleplon and Ketoconazole interact?
Ketoconazole slows down the liver's ability to process zaleplon, which can lead to higher levels of the sleep medicine in your blood.
Understanding the Zaleplon and Ketoconazole Interaction
FDA-approved prescribing information for these two drugs flags their combination as a minor-severity interaction. Zaleplon belongs to the Non-Benzodiazepine Hypnotic (Z-Drug) 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 process zaleplon, which can lead to higher levels of the sleep 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. Zaleplon has 16 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 lower your dose of zaleplon. 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 Zaleplon 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.