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

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.

SUBMITTER: Abraham S

PROVIDER: S-EPMC9580069 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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

Abraham Sonu S Nohria Anju A Neilan Tomas G TG Asnani Aarti A Saji Anu Mariam AM Shah Jui J Lech Tara T Grossman Jason J Abraham George M GM McQuillen Daniel P DP Martin David T DT Sax Paul E PE Dani Sourbha S SS Ganatra Sarju S

Journal of the American College of Cardiology 20221012 20

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 t ...[more]

PMID: 36243540

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Project description:BackgroundClinical trials of treatments for coronavirus disease 2019 (Covid-19) have not shown a significant benefit of postexposure prophylaxis.MethodsWe conducted a phase 2-3 double-blind trial to assess the efficacy and safety of nirmatrelvir-ritonavir in asymptomatic, rapid antigen test-negative adults who had been exposed to a household contact with Covid-19 within 96 hours before randomization. The participants were randomly assigned in a 1:1:1 ratio to receive nirmatrelvir-ritonavir (300 mg of nirmatrelvir and 100 mg of ritonavir) every 12 hours for 5 days or for 10 days or matching placebo for 5 or 10 days. The primary end point was the development of symptomatic SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection, confirmed on reverse-transcriptase-polymerase-chain-reaction (RT-PCR) or rapid antigen testing, through 14 days in participants who had a negative RT-PCR test at baseline.ResultsA total of 2736 participants were randomly assigned to a trial group - 921 to the 5-day nirmatrelvir-ritonavir group, 917 to the 10-day nirmatrelvir-ritonavir group, and 898 to the placebo group. Symptomatic, confirmed SARS-CoV-2 infection developed by day 14 in 2.6% of the participants in the 5-day nirmatrelvir-ritonavir group, 2.4% of those in the 10-day nirmatrelvir-ritonavir group, and 3.9% of those in the placebo group. In each nirmatrelvir-ritonavir group, the percentage of participants in whom symptomatic, confirmed SARS-CoV-2 infection developed did not differ significantly from that in the placebo group, with risk reductions relative to placebo of 29.8% (95% confidence interval [CI], -16.7 to 57.8; P = 0.17) in the 5-day nirmatrelvir-ritonavir group and 35.5% (95% CI, -11.5 to 62.7; P = 0.12) in the 10-day nirmatrelvir-ritonavir group. The incidence of adverse events was similar across the trial groups, with dysgeusia being the most frequently reported adverse event (in 5.9% and 6.8% of the participants in the 5-day and 10-day nirmatrelvir-ritonavir groups, respectively, and in 0.7% of those in the placebo group).ConclusionsIn this placebo-controlled trial, postexposure prophylaxis with nirmatrelvir-ritonavir for 5 or 10 days did not significantly reduce the risk of symptomatic SARS-CoV-2 infection. (Funded by Pfizer; ClinicalTrials.gov number, NCT05047601.).

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

Publications

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

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