Pharmacokinetic interaction between verapamil and ritonavir-boosted nirmatrelvir: implications for the management of COVID-19 in patients with hypertension

Abstract

A woman in her 80s was brought to the emergency department for acute onset of generalised weakness, lethargy and altered mental state. The emergency medical service found her to have symptomatic bradycardia, and transcutaneous pacing was done. Medical history was notable for hypertension, hyperlipidaemia, type 2 diabetes, and a recently diagnosed SARS-CoV-2 (COVID-19) infection for which she was prescribed ritonavir-boosted nirmatrelvir (Paxlovid) two days before the presentation. On arrival at the hospital, she was found to have marked bradycardia with widened QRS, hyperglycaemia and metabolic acidosis. Transvenous pacing along with pressor support and insulin were initiated, and she was admitted to the intensive care unit. Drug interaction between ritonavir-boosted nirmatrelvir and verapamil leading to verapamil toxicity was suspected of causing her symptoms, and both drugs were withheld. She reverted to sinus rhythm on the fourth day, and the pacemaker was discontinued.