Complete Heart Block Triggered by Nirmatrelvir-Ritonavir and Verapamil

Ritonavir-boosted nirmatrelvir (Paxlovid) is a treatment for COVID-19. However, ritonavir, a cytochrome P450 (CYP) CYP3A4 inhibitor, poses a risk of significant drug-drug interactions. In our case, coprescribed nirmatrelvir-ritonavir and verapamil, with concomitant acute kidney injury, resulted in complete heart block and shock. Following fluid resuscitation, blood pressure support with norepinephrine, and calcium therapy for verapamil toxicity, the patient recovered and was discharged home in normal sinus rhythm. To our knowledge, only 2 cases with this drug-drug interaction have been documented, making this a rare, but serious interaction poorly described in the literature. Understanding the pharmacokinetic relationship between these 2 medications and the risks of coprescribing them is crucial for both diagnosing toxicity and reducing preventable morbidity and mortality.

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Publication Details

Journal
JACC Case Reports
Published
2025-03-17
DOI
https://doi.org/10.1016/j.jaccas.2025.103238
Citations
1
Primary Topic
Pharmacogenetics and Drug Metabolism
Type
article
Field-Weighted Citation Impact
1.56
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article

Complete Heart Block Triggered by Nirmatrelvir-Ritonavir and Verapamil

Lawrence Rosenthal, Michelle Nabi, Michael Mankbadi, Evan Offord et al.
1 citations
JACC Case Reports
Pharmacogenetics and Drug Metabolism
1.56
article

Complete Heart Block Triggered by Nirmatrelvir-Ritonavir and Verapamil

Lawrence Rosenthal, Michelle Nabi, Michael Mankbadi, Evan Offord, Alexandra Marchetta
article en
1 citations

Abstract

Ritonavir-boosted nirmatrelvir (Paxlovid) is a treatment for COVID-19. However, ritonavir, a cytochrome P450 (CYP) CYP3A4 inhibitor, poses a risk of significant drug-drug interactions. In our case, coprescribed nirmatrelvir-ritonavir and verapamil, with concomitant acute kidney injury, resulted in complete heart block and shock. Following fluid resuscitation, blood pressure support with norepinephrine, and calcium therapy for verapamil toxicity, the patient recovered and was discharged home in normal sinus rhythm. To our knowledge, only 2 cases with this drug-drug interaction have been documented, making this a rare, but serious interaction poorly described in the literature. Understanding the pharmacokinetic relationship between these 2 medications and the risks of coprescribing them is crucial for both diagnosing toxicity and reducing preventable morbidity and mortality.

JACC Case ReportsVol. 30(8)
UMass Memorial Health Care (US), University of Massachusetts Chan Medical School (US), UMass Memorial Medical Center (US)
Zero hunger
Openalex Percentile: Top 22%
Pharmacogenetics and Drug Metabolism
1.56
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