What are the potential drug interactions with Paxlovid (nirmatrelvir/ritonavir)?

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]. Co-administration with other CYP3A substrates may require a dose adjustment or additional monitoring as shown in Table 1.
2. 2 Potential for Other Drugs to Affect PAXLOVID Nirmatrelvir and ritonavir are CYP3A substrates; therefore, drugs that induce CYP3A may decrease nirmatrelvir and ritonavir plasma concentrations and reduce PAXLOVID therapeutic effect [see Contraindications (4) and Drug Interactions (7.3) Table 1].
3. 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. The healthcare provider should consult other appropriate resources such as the prescribing information for the interacting drug for comprehensive information on dosing or monitoring with concomitant use of a strong CYP3A inhibitor such as ritonavir Table 1: Established and Other Potentially Significant Drug Interactions Drug Class Drugs within Class Effect on Concentration Clinical 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 has several significant drug interactions due to its strong inhibition of CYP3A and inhibition of CYP2D6, P-gp, and OATP1B1. Some key interactions include:

• Contraindications:
  • Alpha 1-adrenoreceptor antagonists like alfuzosin and tamsulosin
  • Antiarrhythmics like amiodarone, dronedarone, flecainide, propafenone, and quinidine
  • Anticancer drugs like apalutamide
• Dose adjustments or monitoring may be required for:
  • Antiarrhythmics like lidocaine and disopyramide
  • Anticoagulants like warfarin, rivaroxaban, dabigatran, and apixaban
  • Anticancer drugs like abemaciclib, ceritinib, dasatinib, encorafenib, ibrutinib, ivosidenib, neratinib, nilotinib, venetoclax, vinblastine, and vincristine It is essential to review all medications taken by the patient and consult other resources for comprehensive information on dosing or monitoring with concomitant use of PAXLOVID 1.

From the Research

Paxlovid has significant drug interactions that require careful medication review before starting treatment, and it is crucial to inform your healthcare provider about all medications you take, including over-the-counter drugs and supplements, to avoid potentially serious side effects 2.

Medication Interactions with Paxlovid

Paxlovid contains nirmatrelvir and ritonavir, with ritonavir being a strong inhibitor of the CYP3A4 enzyme that metabolizes many medications. Some medications absolutely cannot be taken with Paxlovid, including:

• Certain statins (lovastatin, simvastatin)
• Heart rhythm medications (amiodarone, flecainide)
• Sedatives (triazolam, midazolam)
• Ergot derivatives For other medications like atorvastatin, rosuvastatin, and certain blood thinners (apixaban, rivaroxaban), temporary dose adjustments or brief medication pauses may be needed during the 5-day Paxlovid course 3.

Management of Drug Interactions

Immunosuppressants (tacrolimus, cyclosporine), psychiatric medications, and certain blood pressure medications also require careful management.

• Always inform your healthcare provider about all medications you take, including over-the-counter drugs and supplements, before starting Paxlovid.
• Your doctor may need to adjust dosages or temporarily switch medications to safely administer Paxlovid 4.

Rationale for Caution

These interactions occur because ritonavir blocks the breakdown of many drugs, potentially causing dangerously high levels in the bloodstream that could lead to serious side effects 5.

Clinical Implications

Given the potential for significant drug interactions, it is essential to carefully review a patient's medication list before initiating Paxlovid treatment, and to closely monitor for any adverse effects during the treatment course 6.