Nirmatrelvir/Ritonavir and Midazolam Interaction
Drug interaction information between Nirmatrelvir/Ritonavir and Midazolam.
Nirmatrelvir/Ritonavir and Midazolam have a documented major interaction in FDA labeling.
FDA drug labeling documents a major-severity interaction between Nirmatrelvir/Ritonavir and Midazolam. This page displays the available source-record category and label text. The category is not an individual risk estimate or medication-combination direction.
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.
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.
Nirmatrelvir/Ritonavir Also Interacts With
- Simvastatin major
- Lovastatin major
- Sildenafil major
- Carbamazepine major
- Rifampin major
Midazolam Also Interacts With
- Darunavir major
- Itraconazole major
- Ketoconazole moderate
- Verapamil moderate
- Erythromycin moderate
Frequently Asked Questions
What SPL severity band is on file for Nirmatrelvir/Ritonavir + Midazolam?
Compiled FDA labeling labels this pair major. That is a source-record field, not an individual medication-combination decision.
Which drug in this pair has the larger labeled-interaction portfolio?
Nirmatrelvir/Ritonavir has 86 labeled pairs on file vs Midazolam's 39. In the major band specifically: Nirmatrelvir/Ritonavir has 23 (also Simvastatin, Lovastatin, Sildenafil, Carbamazepine); Midazolam has 3 (also Darunavir, Itraconazole).
What mechanism field is on file for Nirmatrelvir/Ritonavir and Midazolam?
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.
Nirmatrelvir/Ritonavir carries more major-labeled pairs than Midazolam
SPL source-record counts only. This page's band is major · classes on file: Nirmatrelvir/Ritonavir (Antiviral (Protease Inhibitor Combination)); Midazolam (Benzodiazepine).
Nirmatrelvir/Ritonavir has 23 major-labeled pairs vs Midazolam's 3.
23 major · 30 moderate · 33 minor · 86 total
- Other major peers for Nirmatrelvir/Ritonavir
- Simvastatin
- Lovastatin
- Sildenafil
- Carbamazepine
3 major · 9 moderate · 27 minor · 39 total
- Other major peers for Midazolam
- Darunavir
- Itraconazole
Sources: FDA Drug Labels (SPL) via openFDA (2026). This is for informational purposes only and is not medical advice. This registry does not provide individual medication-combination directions.
Read our methodology - how this data is sourced, computed, and verified.