Rifampin and Nirmatrelvir/Ritonavir Interaction

Drug interaction information between Rifampin and Nirmatrelvir/Ritonavir.

Rifampin and Nirmatrelvir/Ritonavir have a documented major interaction in FDA labeling.

FDA drug labeling documents a major-severity interaction between Rifampin and Nirmatrelvir/Ritonavir. This page displays the available source-record category and label text. The category is not an individual risk estimate or medication-combination direction.

Drug A

Rifampin

Rifamycin Antibiotic

Drug B

Nirmatrelvir/Ritonavir

Antiviral (Protease Inhibitor Combination)

How They Interact

Rifampin causes the body to break down nirmatrelvir/ritonavir too quickly, which lowers the amount of medicine in your blood. This can make the treatment less effective and may lead to the virus becoming resistant.

FDA Label Information

Antimycobacterial rifampin, rifapentine ↓ nirmatrelvir/ritonavir Co-administration contraindicated due to potential loss of virologic response and possible resistance.

Frequently Asked Questions

What SPL severity band is on file for Rifampin + Nirmatrelvir/Ritonavir?

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?

Rifampin has 137 labeled pairs on file vs Nirmatrelvir/Ritonavir's 86. In the major band specifically: Rifampin has 8 (also Darunavir, Bictegravir, Glecaprevir/Pibrentasvir, Pitavastatin); Nirmatrelvir/Ritonavir has 23 (also Simvastatin, Lovastatin, Sildenafil, Carbamazepine).

What mechanism field is on file for Rifampin and Nirmatrelvir/Ritonavir?

Rifampin causes the body to break down nirmatrelvir/ritonavir too quickly, which lowers the amount of medicine in your blood. This can make the treatment less effective and may lead to the virus becoming resistant.

Nirmatrelvir/Ritonavir carries more major-labeled pairs than Rifampin

SPL source-record counts only. This page's band is major · classes on file: Rifampin (Rifamycin Antibiotic); Nirmatrelvir/Ritonavir (Antiviral (Protease Inhibitor Combination)).

Nirmatrelvir/Ritonavir has 23 major-labeled pairs vs Rifampin's 8.

Rifampin

8 major · 26 moderate · 103 minor · 137 total

Nirmatrelvir/Ritonavir

23 major · 30 moderate · 33 minor · 86 total

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.