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

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

Publication date: Dec 01, 2024

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.

Concepts Keywords
Coronavirus Acute Disease
Organ Anticoagulants
Outpatient Anticoagulants
Pharmacokinetic anticoagulation
Severe COVID-19
COVID-19
COVID-19 Drug Treatment
Drug Combinations
Drug Combinations
Drug Interactions
drug interactions
Female
Humans
International Normalized Ratio
Lopinavir
Lopinavir
lopinavir-ritonavir drug combination
Middle Aged
Paxlovid (nirmatrelvir/ritonavir)
Ritonavir
Ritonavir
Warfarin
Warfarin
warfarin

Semantics

Type Source Name
drug DRUGBANK Ritonavir
drug DRUGBANK Warfarin
disease MESH COVID-19
disease MESH drug interaction
pathway KEGG Coronavirus disease
disease MESH infection
disease MESH Acute Disease
drug DRUGBANK Lopinavir

Original Article

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