A 2022 American College of Cardiology (ACC) clinical bulletin board provides a list of drug-drug interactions with nirmatrelvir/ritonavir (Paxlovid) and select cardiovascular medications. Interaction effects between Paxlovid and direct oral anticoagulants (DOACs) in specific are potentially increased risk of bleeding due to increased DOACs concentration with concomitant use; thus, the management recommendation is to hold DOAC during Paxlovid therapy. This list of information is intended for reference only and does not replace clinical judgment and shared decision-making for individualized patients. [1]
The National Institutes of Health (NIH) COVID-19 treatment guidelines list direct oral DOACs as common outpatient medications that have clinically relevant drug-drug interactions with ritonavir-boosted nirmatrelvir. Additionally, the panel recommends adjusting doses of concomitant apixaban and monitoring for adverse effects. While specific dose adjustments are not provided, temporarily withholding medication (if clinically appropriate) or using an alternative agent may be considered if the doses of interacting medications cannot be adjusted. [2]
The Infectious Disease Society of America (IDSA) guidelines for the management of drug interactions with Paxlovid recommend reducing the dose of apixaban 5 mg and 10 mg by 50% until 3 days after treatment with Paxlovid. For patients taking apixaban 2.5 mg, the panel recommends avoiding the use of Paxlovid. [3]
The Scientific and Standardization Committee (SSC) of the International Society on Thrombosis and Haemostasis (ISTH) suggests that when a patient is taking a DOAC and may be eligible to receive Paxlovid, an individualized, patient-centric approach should be taken. Several management options were suggested for patients receiving potentially interacting medications, including temporarily holding the dose of DOAC, reducing the dose, and monitoring the patient closely for at least seven days from the time of Paxlovid initiation. While low molecular weight heparin may be used as alternative anticoagulation therapy, it was recommended to continue oral anticoagulants whenever possible. The panel recommended against switching DOACs to warfarin due to increased variability of INR in patients with newly diagnosed COVID-19. [4]
A 2022 review discussed the management of drug-drug interactions (DDI) between Paxlovid and anticoagulants, including DOACs. Since DOACs are substrates of cytochrome P450 (CYP) 3A4 and P-glycoprotein (P-gp), significant DDIs are expected when these agents are coadministered with ritonavir, a potent CYP3A4 and P-gp inhibitor. However, no adverse outcomes were reported in HIV-infected patients treated with low-dose apixaban while on ritonavir-boosted antiretroviral therapy (Table 1 and Table 2). Despite prescribing information for apixaban recommending administering the medication at a reduced dose (2.5 mg BID) when combined with strong CYP3A4 and P-gp inhibitors (e.g., ritonavir), it was suggested to avoid concomitant use of Paxlovid with apixaban. [5]
A 2022 commentary provided an algorithmic approach to manage drug-drug interactions of oral anticoagulants with Paxlovid. The authors recommended reducing the dose of apixaban to 2.5 mg BID when Paxlovid is used. For patients already taking apixaban at a dose of 2.5 mg daily, concurrent use of Paxlovid with apixaban should be avoided. [6]
A case series described the successful use of reduced-dose apixaban in six human immunodeficiency virus (HIV) patients who were receiving ritonavir- or cobicistat-boosted antiretroviral therapy (ART) (see Table 1). The case series suggests apixaban or dabigatran may be safely used in HIV patients taking ART regimens containing ritonavir, and apixaban may be concomitantly used with cobicistat. [7]