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AI-Generated response:

Interactions between Warfarin and Paxlovid

Answer generated on June 4, 2024

The AI-generated responses are for illustration purposes only and should not be used for medical purposes.

Coadministration of Warfarin and Paxlovid requires close monitoring of INR due to potential alterations in Warfarin exposure, which may increase bleeding risk or reduce efficacy.[1-3]

  • Warfarin is metabolized by CYP3A4, CYP2C9, and CYP1A2, and Paxlovid's component ritonavir is a strong inhibitor of CYP3A4 and also affects other cytochrome P450 enzymes.[1-2]

  • Ritonavir's inhibition of CYP3A4 can lead to increased plasma concentrations of Warfarin, particularly the more potent S-enantiomer, potentially increasing the anticoagulant effect and bleeding risk.[2]

  • It is recommended to adjust the Warfarin dosage based on the patient's INR response when coadministered with Paxlovid.[2]

  • The FDA advises that the potential for drug interactions should be considered before and during Paxlovid therapy, especially with drugs like Warfarin that are metabolized by CYP3A.[3]

  • Specific monitoring and possible dose adjustment are necessary to manage the interaction and maintain therapeutic efficacy and safety.[3]

Additional info

Given the complex interaction between Warfarin and Paxlovid, particularly through the inhibition of CYP3A4 by ritonavir, careful management is crucial. The alteration in Warfarin's metabolism can lead to significant changes in its anticoagulant effect, necessitating frequent INR monitoring and potential dose adjustments. This interaction underscores the importance of personalized medicine and the need for vigilant monitoring when these medications are used concurrently. The physician should be prepared to make timely adjustments to the Warfarin dosage based on INR results to maintain the balance between preventing thrombotic events and avoiding excessive bleeding.

References

Reference 1

1.

Elsevier ClinicalKey Drug Monograph

Content last updated: May 5, 2024.

Interactions PAXLOVID: (Moderate) Closely monitor the INR if coadministration of warfarin with ritonavir is necessary as concurrent use may alter the exposure of warfarin leading to increased bleeding risk or reduced efficacy. Warfarin is a substrate of CYP3A4, CYP2C9, and CYP1A2 and ritonavir is a strong CYP3A4 inhibitor as well as a CYP1A4, CYP2C9, and CYP3A4 inducer.

Interactions PAXLOVID: (Moderate) Closely monitor the INR if coadministration of coumadin with ritonavir is necessary as concurrent use may alter the exposure of coumadin leading to increased bleeding risk or reduced efficacy. Coumadin is a substrate of CYP3A4, CYP2C9, and CYP1A2 and ritonavir is a strong CYP3A4 inhibitor as well as a CYP1A4, CYP2C9, and CYP3A4 inducer.

Interactions PAXLOVID: (Moderate) Closely monitor the INR if coadministration of jantoven with ritonavir is necessary as concurrent use may alter the exposure of jantoven leading to increased bleeding risk or reduced efficacy. Jantoven is a substrate of CYP3A4, CYP2C9, and CYP1A2 and ritonavir is a strong CYP3A4 inhibitor as well as a CYP1A4, CYP2C9, and CYP3A4 inducer.

Reference 2

2.

Elsevier ClinicalKey Drug Monograph

Content last updated: May 4, 2024.

Interactions Warfarin: (Moderate) Closely monitor INR and adjust the warfarin dosage as appropriate based on response if warfarin and ritonavir coadministration is necessary. Ritonavir has a complex effect on warfarin concentrations which may result in increased bleeding risk or reduced warfarin efficacy. Warfarin is a mixture of S- and R-enantiomers: the S-enantiomer exhibits 2 to 5 times more anticoagulant activity than the R-enantiomer, but the R-enantiomer has a slower clearance. Ritonavir has been observed to increase overall exposure to the S-enantiomer of warfarin by 9% and decrease overall exposure to the R-enantiomer of warfarin by 33%.

Reference 3

3.

Food and Drug Administration (DailyMed).

Publish date: October 3, 2023.

Drug Interactions 7 DRUG INTERACTIONS Co-administration of Paxlovid (nirmatrelvir and ritonavir) can alter the plasma concentrations of other drugs and other drugs may alter the plasma concentrations of Paxlovid (nirmatrelvir and ritonavir). Consider the potential for drug interactions prior to and during Paxlovid (nirmatrelvir and ritonavir) therapy and review concomitant medications during Paxlovid (nirmatrelvir and ritonavir) therapy. ( 4, 5.1, 7, 12.3 ) 7.1 Potential for Paxlovid (nirmatrelvir and ritonavir) to Affect Other Drugs Paxlovid (nirmatrelvir and ritonavir) (nirmatrelvir co-packaged with ritonavir) is a strong inhibitor of CYP3A, and an inhibitor of CYP2D6, P-gp and OATP1B1. Co-administration of Paxlovid (nirmatrelvir and ritonavir) 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 (nirmatrelvir and ritonavir) 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.

Drug Interactions Table 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.</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="top"><paragraph>Anticoagulants </paragraph></td><td styleCode="Rrule " valign="top"><paragraph>warfarin</paragraph></td><td styleCode="Rrule " valign="top"><paragraph>&#x2191;&#x2193; warfarin</paragraph></td><td styleCode="Rrule " valign="top"><paragraph>Closely monitor international normalized ratio (INR) if co-administration with warfarin is necessary.</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="top"/><td styleCode="Rrule " valign="top"><paragraph>rivaroxaban</paragraph></td><td styleCode="Rrule " valign="top"><paragraph>&#x2191; rivaroxaban</paragraph></td><td styleCode="Rrule " valign="top"><paragraph>Increased bleeding risk with rivaroxaban. Avoid concomitant use.

Drug Interactions 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 See Pharmacokinetics, Drug Interaction Studies Conducted with Paxlovid (nirmatrelvir and ritonavir) (12.3). ↑ dabigatran Increased bleeding risk with dabigatran.

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