Phenytoin and Nirmatrelvir/Ritonavir Interaction

Drug interaction information between Phenytoin and Nirmatrelvir/Ritonavir.

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

FDA drug labeling documents a major-severity interaction between Phenytoin 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

Phenytoin

Anticonvulsant (Hydantoin)

Drug B

Nirmatrelvir/Ritonavir

Antiviral (Protease Inhibitor Combination)

How They Interact

Phenytoin makes the body get rid of the antiviral medicine too quickly. This prevents the drug from working properly and could allow the virus to become harder to treat.

FDA Label Information

Anticonvulsants carbamazepine , phenobarbital, primidone, phenytoin ↓ nirmatrelvir/ritonavir Co-administration contraindicated due to potential loss of virologic response and possible resistance [see Contraindications (4) ] .

Frequently Asked Questions

What SPL severity band is on file for Phenytoin + 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?

Phenytoin has 147 labeled pairs on file vs Nirmatrelvir/Ritonavir's 86. In the major band specifically: Phenytoin has 4 (also Posaconazole, Ranolazine, Voriconazole); Nirmatrelvir/Ritonavir has 23 (also Simvastatin, Lovastatin, Sildenafil, Carbamazepine).

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

Phenytoin makes the body get rid of the antiviral medicine too quickly. This prevents the drug from working properly and could allow the virus to become harder to treat.

Nirmatrelvir/Ritonavir carries more major-labeled pairs than Phenytoin

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

Nirmatrelvir/Ritonavir has 23 major-labeled pairs vs Phenytoin's 4.

Phenytoin

4 major · 23 moderate · 120 minor · 147 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.