What medications does Paxlovid (nirmatrelvir/ritonavir) interact with?

From the FDA Drug Label

7 DRUG INTERACTIONS

1. 1 Potential for PAXLOVID to Affect Other Drugs PAXLOVID (nirmatrelvir co-packaged with ritonavir) is a strong inhibitor of CYP3A, and an inhibitor of CYP2D6, P-gp and OATP1B1 Co-administration of PAXLOVID with drugs that are primarily metabolized by CYP3A and CYP2D6 or are transported by P-gp or OATP1B1 may result in increased plasma concentrations of such drugs and increase the risk of adverse events Co-administration of PAXLOVID with drugs highly dependent on CYP3A for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening events is contraindicated [see Contraindications (4) and Drug Interactions (7.3) Table 1].
2. 3 Established and Other Potentially Significant Drug Interactions Table 1 provides a listing of clinically significant drug interactions, including contraindicated drugs [see Contraindications (4) and Warnings and Precautions (5. 1)]. Drugs listed in Table 1 are a guide and not considered a comprehensive list of all possible drugs that may interact with PAXLOVID. Table 1: Established and Other Potentially Significant Drug Interactions Drug ClassDrugs within ClassEffect on ConcentrationClinical Comments

• See Pharmacokinetics, Clinical Drug Interaction Studies (12. 3). Alpha 1-adrenoreceptor antagonist alfuzosin ↑ alfuzosin Co-administration contraindicated due to potential hypotension [see Contraindications (4)]. Alpha 1-adrenoreceptor antagonist tamsulosin ↑ tamsulosin Avoid concomitant use with PAXLOVID Antianginal ranolazine ↑ ranolazine Co-administration contraindicated due to potential for serious and/or life-threatening reactions [see Contraindications (4)]. Antiarrhythmics amiodarone, dronedarone, flecainide, propafenone, quinidine ↑ antiarrhythmic Co-administration contraindicated due to potential for cardiac arrhythmias [see Contraindications (4)] Antiarrhythmics lidocaine (systemic),disopyramide ↑ antiarrhythmic Caution is warranted and therapeutic concentration monitoring is recommended for antiarrhythmics if available. Anticancer drugs apalutamide ↓ nirmatrelvir/ritonavir Co-administration contraindicated due to potential loss of virologic response and possible resistance [see Contraindications (4)] Anticancer drugs abemaciclib, ceritinib,dasatinib, encorafenib,ibrutinib, ivosidenib, neratinib, nilotinib, venetoclax,vinblastine, vincristine ↑ anticancer drugs Avoid co-administration of encorafenib or ivosidenib due to potential risk of serious adverse events such as QT interval prolongation. Avoid use of neratinib, venetoclax or ibrutinib Co-administration of vincristine and vinblastine may lead to significant hematologic or gastrointestinal side effects. For further information, refer to individual product label for anticancer drug. Anticoagulants warfarin ↑↓ warfarin Closely monitor international normalized ratio (INR) if co-administration with warfarin is necessary rivaroxaban ↑ rivaroxaban Increased bleeding risk with rivaroxaban. Avoid concomitant use. dabigatran* ↑ dabigatran Increased bleeding risk with dabigatran. Depending on dabigatran indication and renal function, reduce dose of dabigatran or avoid concomitant use. Refer to the dabigatran product label for further information apixaban ↑ apixaban Combined P-gp and strong CYP3A inhibitors increase blood levels of apixaban and increase the risk of bleeding. Dosing recommendations for co-administration of apixaban with PAXLOVID depend on the apixaban dose. Refer to the apixaban product label for more information

Paxlovid (nirmatrelvir/ritonavir) interacts with the following medications:

• Alpha 1-adrenoreceptor antagonists: alfuzosin, tamsulosin
• Antiarrhythmics: amiodarone, dronedarone, flecainide, propafenone, quinidine, lidocaine (systemic), disopyramide
• Anticancer drugs: apalutamide, abemaciclib, ceritinib, dasatinib, encorafenib, ibrutinib, ivosidenib, neratinib, nilotinib, venetoclax, vinblastine, vincristine
• Anticoagulants: warfarin, rivaroxaban, dabigatran, apixaban
• Antianginal: ranolazine These interactions may result in increased plasma concentrations of the interacting drug, potentially leading to adverse events. Co-administration of PAXLOVID with certain medications is contraindicated due to the potential for serious and/or life-threatening events. 1

From the Research

Paxlovid can interact with many medications, causing potentially serious problems, and it is crucial to be aware of these interactions to prevent adverse effects, as highlighted in a recent study 2. The main concern is with drugs that are metabolized by the CYP3A enzyme system, as ritonavir (one component of Paxlovid) strongly inhibits this pathway. Some key medications that may interact with Paxlovid include:

• Anticoagulants (warfarin, rivaroxaban)
• Calcium channel blockers (nifedipine, manidipine, verapamil)
• Statins (atorvastatin)
• Immunosuppressants (tacrolimus)
• Antiarrhythmics (amiodarone)
• Antipsychotics (clozapine, quetiapine)
• Ranolazine, as reported in a study published in 2025 2. It is essential to note that these interactions can lead to enhanced toxicities of several drugs, and effective management requires close observation, adjustments to dosage, and assessment of substitute treatments, as emphasized in the study 2. If you're prescribed Paxlovid, provide your healthcare provider with a complete list of all medications you take, including over-the-counter drugs and supplements, to minimize the risk of adverse interactions, as suggested by the evidence 2, 3, 4, 5, 6.