Supratherapeutic INR During Treatment With Nirmatrelvir/Ritonavir and Warfarin and Acute Illness With COVID-19: A Case Report

Background: Several studies have examined INR fluctuations using pharmacokinetic (PK) models or post-hoc INR values after completing nirmatrelvir/ritonavir, but further study of the effects of the drug interaction with warfarin during treatment is necessary. Case Summary: Nirmatrelvir/ritonavir is largely utilized in the outpatient setting so data regarding INR trends in hospitalized patients on warfarin is limited. However, many who receive nirmatrelvir/ritonavir outpatient experience difficulty with presenting to clinic for INR checks due to feeling acutely ill along with isolation precautions. We present the case of a patient receiving warfarin and utilizing home INR testing for monitoring. After diagnosis of coronavirus disease of 2019 (COVID-19), she was started on nirmatrelvir/ritonavir on day five after testing positive. Most recent INR prior to the start of therapy was 2.7 and had been stable on the same dose for months prior to infection. On day two of nirmatrelvir/ritonavir, her INR rose to 4.0 on home point of care INR testing. Despite reducing her dose of warfarin by 15%, her INR remained supratherapeutic the day after completing nirmatrelvir/ritonavir (4.0) and for several checks after. One month after completion of therapy, her INR returned to therapeutic levels. Practice Implications: While PK models and case series have hypothesized both potential increases or decreases in INR with the nirmatrelvir/ritonavir and warfarin interaction, COVID-19 infection itself can cause several pharmacodynamic changes which can increase INR, including decreased appetite and, in severe cases, organ dysfunction. This case provides real-world insight into the drug interaction between nirmatrelvir/ritonavir and the drug-disease state interaction between warfarin and COVID-19.