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Complete Heart Block Triggered by Nirmatrelvir-Ritonavir and Verapamil

Offord et al., JACC: Case Reports, doi:10.1016/j.jaccas.2025.103238, Mar 2025
Case report of a 58-year-old woman who developed complete heart block and shock due to a drug-drug interaction between paxlovid and verapamil, exacerbated by acute kidney injury and liver dysfunction. This case highlights potentially lethal interactions caused by ritonavir's potent inhibition of CYP3A4, which is required for verapamil metabolism, resulting in verapamil toxicity.
Offord et al., 17 Mar 2025, USA, peer-reviewed, 5 authors.
Complete Heart Block Triggered by Nirmatrelvir-Ritonavir and Verapamil
MD Evan Offord, MD Michelle Nabi, MD Michael Mankbadi, MD Alexandra Marchetta, MD Lawrence Rosenthal
JACC: Case Reports, doi:10.1016/j.jaccas.2025.103238
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 Rep.
References
Alshaya, Alhamed, Althewaibi, Calcium channel blocker toxicity: a practical approach, J Multidiscip Healthc, doi:10.2147/JMDH.S374887
Azanza, Mensa, Del Castillo, Interactions listed in the Paxlovid fact sheet, classified according to risks, pharmacological groups, and consequences, Rev Esp Quimioter, doi:10.37201/req/054.2022
Eichelbaum, Ende, Remberg, Schomerus, Dengler, The metabolism of DL-[14C]verapamil in man, Drug Metab Dispos
Enstrom, Longbrake, Bernard, Gage, Cardiogenic shock due to Paxlovid interaction, JACC Case Rep, doi:10.1016/S0735-1097(23)02916-9
Fravel, Ernst, Drug interactions with antihypertensives, Curr Hypertens Rep, doi:10.1007/s11906-021-01131-y
Graudins, Lee, Druda, Calcium channel antagonist and beta-blocker overdose: antidotes and adjunct therapies, Br J Clin Pharmacol, doi:10.1111/bcp.12763
Haque, Mahar, Hussain, Sloane, Pharmacokinetic interaction between verapamil and ritonavir-boosted nirmatrelvir: implications for the management of COVID-19 in patients with hypertension, doi:10.1136/bcr-2022-252677
Loos, Beijnen, Schinkel, The mechanism-based inactivation of CYP3A4 by ritonavir: what mechanism?, Int J Mol Sci, doi:10.3390/ijms23179866
Naranjo, Busto, Sellers, A method for estimating the probability of adverse drug reactions, Clin Pharmacol Ther, doi:10.1038/clpt.1981.154
Tracy, Korzekwa, Gonzalez, Wainer, Cytochrome P450 isoforms involved in metabolism of the enantiomers of verapamil and norverapamil, Br J Clin Pharmacol, doi:10.1046/j.1365-2125.1999.00923.x
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