PAXLOVID drug interaction

A physician prescribed PAXLOVID (nirmatrelvir and   ritonavir) for a 34-year-old patient with flu-like symptoms who tested positive for coronavirus disease 2019 (COVID-19). On day 3 of treatment, the patient presented with signs and symptoms of fatigue and bradycardia, with a heart rate below 40 beats per minute. The physician referred the patient to the emergency department (ED) for further evaluation, where it was discovered that the patient had been taking ivabradine for premature ventricular contractions. Ivabradine is metabolized by the cytochrome P450 3A4 (CYP3A4) enzyme, and the ritonavir component of Paxlovid is a strong CYP3A4 inhibitor. Thus, concomitant use of Paxlovid and ivabradine is contraindicated due to the risk of ivabradine accumulation and toxicity, which could lead to bradycardia, hypotension, and heart failure. Increased plasma concentrations of ivabradine may also exacerbate bradycardia and conduction disturbances. Fortunately, the patient was monitored in the ED for 24 hours, recovered, and was discharged home.

Educate prescribers, as well as patients, about the potential for Paxlovid drug interactions. Also, organizations should test their electronic health records and/or pharmacy computer systems to ensure they provide alerts for this and other drug-drug interactions. Incidentally, the practitioner who reported this event to ISMP mentioned that the prescriber was not familiar with the patient’s medical history. Paxlovid is not a drug that should be casually prescribed, without reviewing the patient’s current medication list for potential drug-drug interactions. The US Food and Drug Administration’s (FDA) Paxlovid Patient Eligibility Screening Checklist Tool for Prescribers can be used for screening but does not currently list ivabradine as a drug with potentially significant interactions. We have asked FDA to update the screening tool.

In addition to the FDA’s Paxlovid Patient Eligibility Screening Checklist Tool for Prescribers, other resources that practitioners can use to learn about Paxlovid drug-drug interactions include:

• Management of Drug Interactions with Nirmatrelvir/Ritonavir (Paxlovid): Resource for Clinicians, from the Infectious Diseases Society of America (IDSA)

• COVID-19 Drug Interactions, from the University of Liverpool

• Drug-Drug Interactions Between Ritonavir-Boosted Nirmatrelvir (Paxlovid) and Concomitant Medications, from the National Institutes of Health (NIH)