Zolpidem and Ketoconazole Interaction
Drug interaction information between Zolpidem and Ketoconazole.
Zolpidem and Ketoconazole have a documented moderate interaction in FDA labeling.
FDA drug labeling documents a moderate-severity interaction between Zolpidem 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 blocks the liver enzyme that breaks down zolpidem, which causes the sleep medicine to stay in your body longer.
What To Do
Your doctor may need to lower your dose of zolpidem and monitor you for increased sleepiness.
FDA Label Information
John's wort): Combination use may decrease effect ( 7.2 ) Ketoconazole: Combination use may increase effect ( 7.2 ) 7.1 CNS-Active Drugs CNS Depressants Coadministration of Zolpidem with other CNS depressants increases the risk of CNS depression. CYP3A4 Inhibitors Ketoconazole Ketoconazole, a potent CYP3A4 inhibitor, increased the exposure to and pharmacodynamic effects of Zolpidem.
Zolpidem Also Interacts With
- Rifampin moderate
- Imipramine moderate
- Chlorpromazine moderate
- Sertraline minor
- Fluoxetine minor
Ketoconazole Also Interacts With
- Alfuzosin major
- Dronedarone major
- Ranolazine major
- Saxagliptin major
- Sildenafil major
Frequently Asked Questions
Can I take Zolpidem and Ketoconazole together?
This is a moderate interaction. Your doctor may need to lower your dose of zolpidem and monitor you for increased sleepiness.
How serious is the interaction between Zolpidem and Ketoconazole?
This interaction is classified as "moderate" severity by the FDA. Moderate interactions may worsen your condition or change how your medications work.
Why do Zolpidem and Ketoconazole interact?
Ketoconazole blocks the liver enzyme that breaks down zolpidem, which causes the sleep medicine to stay in your body longer.
Understanding the Zolpidem and Ketoconazole Interaction
FDA-approved prescribing information for these two drugs flags their combination as a moderate-severity interaction. Zolpidem 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 blocks the liver enzyme that breaks down zolpidem, which causes the sleep medicine to stay in your body longer. 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. Zolpidem has 9 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 zolpidem and monitor you for increased sleepiness. 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 Zolpidem 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.