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Review
. 2022 Nov 15;80(20):1912-1924.
doi: 10.1016/j.jacc.2022.08.800. Epub 2022 Oct 12.

Cardiovascular Drug Interactions With Nirmatrelvir/Ritonavir in Patients With COVID-19: JACC Review Topic of the Week

Sonu Abraham  1 , Anju Nohria  2 , Tomas G Neilan  3 , Aarti Asnani  4 , Anu Mariam Saji  1 , Jui Shah  1 , Tara Lech  1 , Jason Grossman  1 , George M Abraham  5 , Daniel P McQuillen  6 , David T Martin  2 , Paul E Sax  7 , Sourbha S Dani  1 , Sarju Ganatra  8
Affiliations
Review

Cardiovascular Drug Interactions With Nirmatrelvir/Ritonavir in Patients With COVID-19: JACC Review Topic of the Week

Sonu Abraham et al. J Am Coll Cardiol. .

Abstract

Nirmatrelvir-ritonavir (NMVr) is used to treat symptomatic, nonhospitalized patients with coronavirus disease-2019 (COVID-19) who are at high risk of progression to severe disease. Patients with cardiovascular risk factors and cardiovascular disease are at a high risk of developing adverse events from COVID-19 and as a result have a higher likelihood of receiving NMVr. Ritonavir, the pharmaceutical enhancer used in NMVr, is an inhibitor of the enzymes of CYP450 pathway, particularly CYP3A4 and to a lesser degree CYP2D6, and affects the P-glycoprotein pump. Co-administration of NMVr with medications commonly used to manage cardiovascular conditions can potentially cause significant drug-drug interactions and may lead to severe adverse effects. It is crucial to be aware of such interactions and take appropriate measures to avoid them. In this review, we discuss potential drug-drug interactions between NMVr and commonly used cardiovascular medications based on their pharmacokinetics and pharmacodynamic properties.

Keywords: COVID-19; SARS-CoV-2; cardiovascular medications; drug-drug interactions; nirmatrelvir-ritonavir.

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Conflict of interest statement

Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Figures

None
Graphical abstract
Figure 1
Figure 1
Drug-Drug Interactions of Cardiovascular Medications With Nirmatrelvir-Ritonavir This figure describes potential drug-drug interactions of nirmatrelvir-ritonavir (NMVr) with commonly used cardiovascular (CV) medications along with grade of interactions and recommendations regarding any necessary adjustment in the regimen of CV medications and suitability of NMVr. ACE = angiotensin-converting enzyme.
Figure 2
Figure 2
Nirmatrelvir-Ritonavir Interaction With Enzymes Involved in Drug Metabolism Ritonavir, the pharmaceutical enhancer in nirmatrelvir-ritonavir (NMVr), has significant interactions with other medications. NMVr inhibits CYP3A4 and to a lesser extent CYP2D6. It also inhibits the transmembrane efflux pump P-glycoprotein (P-gp) and the multidrug and toxin extrusion (MATE-1) transporter in the intestinal and renal cells. It inhibits the organic anion transporter polypeptide 1B1 (OATP1B1), which is a transporter on the sinusoidal membrane of the hepatocytes and MRP2 and an efflux transporter on the apical side of the bile canaliculus in the hepatocytes. It has weak inducing effects on CYP1A2, CYP2B6, CYP2C9, and CYP2C19. Some significant DDIs with the substrates of these clinically relevant enzymes are noted. An exhaustive list of all CV medications is not represented. The figure was prepared with the use of Biorender.
Central Illustration
Central Illustration
Decision-Making Algorithm for Patients on Cardiovascular Medications Who Need Nirmatrelvir-Ritonavir This figure illustrates the proposed algorithm to guide the management of cardiovascular (CV) medications for those who require nirmatrelvir-ritonavir (NMVr) for the management of COVID-19.
See this image and copyright information in PMC

References

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