Sildenafil and Nirmatrelvir/Ritonavir Interaction
Drug interaction information between Sildenafil and Nirmatrelvir/Ritonavir.
Sildenafil and Nirmatrelvir/Ritonavir have a documented major interaction in FDA labeling.
FDA drug labeling documents a major-severity interaction between Sildenafil 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
This combination makes sildenafil stay in your body longer and at higher levels, which can cause your blood pressure to drop too low.
What To Do
Avoid this combination if you take sildenafil for high blood pressure in the lungs, or talk to your doctor about a dose change if using it for erectile dysfunction.
FDA Label Information
Pulmonary hypertension agents (PDE5 inhibitors) sildenafil (Revatio ® ) ↑ sildenafil Co-administration of sildenafil with PAXLOVID is contraindicated for use in pulmonary hypertension due to the potential for sildenafil associated adverse events, including visual abnormalities hypotension, prolonged erection, and syncope [see Contraindications (4) ] . sildenafil, tadalafil, vardenafil ↑ sildenafil ↑ tadalafil ↑ vardenafil Dosage adjustment is recommended for use of sildenafil, tadalafil or vardenafil with PAXLOVID when used for erectile dysfunction.
Sildenafil Also Interacts With
- Ketoconazole major
- Erythromycin major
- Itraconazole major
- Darunavir major
- Hydralazine/Isosorbide Dinitrate major
Nirmatrelvir/Ritonavir Also Interacts With
- Simvastatin major
- Lovastatin major
- Carbamazepine major
- Rifampin major
- Lurasidone major
Frequently Asked Questions
Can I take Sildenafil and Nirmatrelvir/Ritonavir together?
This is a major interaction. Avoid this combination if you take sildenafil for high blood pressure in the lungs, or talk to your doctor about a dose change if using it for erectile dysfunction.
How serious is the interaction between Sildenafil 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 Sildenafil and Nirmatrelvir/Ritonavir interact?
This combination makes sildenafil stay in your body longer and at higher levels, which can cause your blood pressure to drop too low.
Understanding the Sildenafil and Nirmatrelvir/Ritonavir Interaction
FDA-approved prescribing information for these two drugs flags their combination as a major-severity interaction. Sildenafil belongs to the PDE5 Inhibitor 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: This combination makes sildenafil stay in your body longer and at higher levels, which can cause your blood pressure to drop too low. 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. Sildenafil has 10 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 this combination if you take sildenafil for high blood pressure in the lungs, or talk to your doctor about a dose change if using it for erectile dysfunction. 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 Sildenafil 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.