Nirmatrelvir and ritonavir and Sildenafil interaction

Nirmatrelvir and ritonavir and Sildenafil: both prescribing labels flag this combination with the strongest language, such as a contraindication, a boxed warning, or an instruction to avoid it.

Major

Do not combine without a prescriber's guidance. The label language below is the strongest FDA uses.

What the FDA labels say

From the Nirmatrelvir and ritonavir (Paxlovid) label · effective 2026-02-19

Major

…ubrogepant • Mineralocorticoid receptor antagonists: finerenone • Non-opioid analgesic (selective blocker of Na v 1.8 sodium channels): suzetrigine • Opioid antagonists: naloxegol • PDE5 inhibitor: sildenafil (Revatio ® ) when used for pulmonary arterial hypertension (PAH) • Sedative/hypnotics: triazolam, oral midazolam • Serotonin receptor 1A agonist/serotonin…

Contraindicationsby drug classView label on DailyMed
Major

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) ] .

Drug interactionsby drug classView label on DailyMed
Major

Pulmonary hypertension agents (PDE5 inhibitors) tadalafil (Adcirca ® ) ↑ tadalafil Avoid concomitant use of tadalafil with PAXLOVID for pulmonary hypertension.

Drug interactionsby drug classView label on DailyMed
Major

Erectile dysfunction agents (PDE5 inhibitors) avanafil ↑ avanafil Do not use PAXLOVID with avanafil because a safe and effective avanafil dosage regimen has not been established. sildenafil, tadalafil, vardenafil ↑ sildenafil ↑ tadalafil ↑ vardenafil Dosage adjustment is recommended for use of sildenafil, tadalafil or vardenafil with PAXLOVID when used for erectile…

Drug interactionsby drug classView label on DailyMed

From the Sildenafil label · effective 2026-07-17

Moderate

In patients taking strong CYP inhibitors such as ritonavir, sildenafil exposure is increased.

Warnings and precautionsnames Nirmatrelvir and ritonavirView label on DailyMed
Moderate

Adverse Reactions with the Concomitant Use of Ritonavir The concomitant administration of the protease inhibitor ritonavir substantially increases serum concentrations of sildenafil (11-fold increase in AUC).

Warnings and precautionsnames Nirmatrelvir and ritonavirView label on DailyMed
Moderate

To decrease the chance of adverse reactions in patients taking ritonavir, the maximum recommended dosage and dosing frequency of SILDENAFIL ORAL FILM is 25 mg once in a 48-hour period [see Dosage and Administration ( 2.2 ), Drug Interactions ( 7.4 ), and Clinical Pharmacology ( 12.3 ) ].

Warnings and precautionsnames Nirmatrelvir and ritonavirView label on DailyMed
Moderate

Ritonavir: Do not exceed a maximum single dose of 25 mg in a 48- hour period.

Drug interactionsnames Nirmatrelvir and ritonavirView label on DailyMed
Moderate

CYP3A4 inhibitors (e.g., ritonavir, ketoconazole, itraconazole, erythromycin) increase SILDENAFIL ORAL FILM exposure.

Drug interactionsby drug classView label on DailyMed

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Not medical advice. Interaction Checker quotes FDA label text and NIH fact sheets. Whether an interaction matters for you depends on doses, timing, kidney and liver function, and other conditions. Confirm with a pharmacist or prescriber.