Midazolam and Nirmatrelvir/Ritonavir Interaction
Drug interaction information between Midazolam and Nirmatrelvir/Ritonavir.
Midazolam and Nirmatrelvir/Ritonavir have a documented major interaction in FDA labeling.
FDA drug labeling documents a major-severity interaction between Midazolam and Nirmatrelvir/Ritonavir. 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
Nirmatrelvir/ritonavir makes midazolam stay in your body much longer and at higher levels than normal. This can cause you to become dangerously sleepy or have trouble breathing.
What To Do
Avoid taking the oral form of this medicine together; if the injected form is used, your doctor must monitor you closely and may lower your dose.
FDA Label Information
Sedative/hypnotics triazolam, oral midazolam ↑ triazolam ↑ midazolam Co-administration contraindicated due to potential for extreme sedation and respiratory depression [see Contraindications (4) ] . midazolam (administered parenterally) ↑ midazolam Co-administration of midazolam (parenteral) should be done in a setting which ensures close clinical monitoring and appropriate medical management in case of respiratory depression and/or prolonged sedation. Dosage reduction for midazolam should be considered, especially if more than a single dose of midazolam is administered.
Midazolam Also Interacts With
- Darunavir major
- Itraconazole major
- Ketoconazole moderate
- Verapamil moderate
- Erythromycin moderate
Nirmatrelvir/Ritonavir Also Interacts With
- Simvastatin major
- Lovastatin major
- Sildenafil major
- Carbamazepine major
- Rifampin major
Frequently Asked Questions
Can I take Midazolam and Nirmatrelvir/Ritonavir together?
This is a major interaction. Avoid taking the oral form of this medicine together; if the injected form is used, your doctor must monitor you closely and may lower your dose.
How serious is the interaction between Midazolam and Nirmatrelvir/Ritonavir?
This interaction is classified as "major" severity by the FDA. Major interactions may be life-threatening or cause serious side effects.
Why do Midazolam and Nirmatrelvir/Ritonavir interact?
Nirmatrelvir/ritonavir makes midazolam stay in your body much longer and at higher levels than normal. This can cause you to become dangerously sleepy or have trouble breathing.
Understanding the Midazolam and Nirmatrelvir/Ritonavir Interaction
FDA-approved prescribing information for these two drugs flags their combination as a major-severity interaction. Midazolam belongs to the Benzodiazepine class and Nirmatrelvir/Ritonavir belongs to the Antiviral (Protease Inhibitor Combination) class - two categories that can collide when co-prescribed. The mechanism described in FDA labeling is: Nirmatrelvir/ritonavir makes midazolam stay in your body much longer and at higher levels than normal. 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. Midazolam has 39 total documented interactions on file in this dataset, and Nirmatrelvir/Ritonavir has 86. 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: Avoid taking the oral form of this medicine together; if the injected form is used, your doctor must monitor you closely and may lower your dose. 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 Midazolam or Nirmatrelvir/Ritonavir 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.