Elevated INR in a COVID‐19 patient after concomitant administration of favipiravir and warfarin: A case report

Abstract

What is known and objective: Favipiravir is a promising treatment candidate for managing coronavirus disease 2019 . Warfarin has many drug interactions, but no interactions with favipiravir have been reported. Case summary: Our patient was taking warfarin for deep vein thrombosis. The international normalized ratio (INR) was stable (1.65 to 2.0); however, it increased to 4.63 after administering favipiravir. The patient had no other factors justifying this change. What is new and conclusion: Favipiravir and warfarin might have previously unidentified drug interactions that elevated the INR. Therefore, INR must be closely monitored when they are concomitantly administered in COVID-19 patients. K E Y W O R D S coronavirus disease of 2019 (COVID-19), cytochrome P-450 (CYP), drug-drug interactions (DDIs), favipiravir, international normalized ratio (INR), warfarin How to cite this article: Sekimoto M, Imai T, Hidaka S, et al.

Potential Drug Interaction Between Favipiravir and Warfarin in Patients With COVID‐19: A Real‐World Observational Study

“…The expression of the relevant proteins should be measured together with the concentration of favipiravir in the body to confirm the interaction. However, according to the previous case report of interaction 14 and the results of this study, coadministration of favipiravir and drugs that are metabolized by the CYP2C8 system should be done with care until the mechanism is better understood. 26…”

“…However, there have never been reports that described favipiravir-warfarin interaction, except for a case report in Japan. 14 Therefore, this study aimed to investigate the interaction between favipiravir and warfarin in patients with indications of both drugs.…”

“…Since favipiravir can inhibit CYP2C8 and warfarin is metabolized by the same enzyme, theoretically, these 2 drugs can have drug interaction. However, there have never been reports that described favipiravir‐warfarin interaction, except for a case report in Japan 14 . Therefore, this study aimed to investigate the interaction between favipiravir and warfarin in patients with indications of both drugs.…”

Drug Interaction Between Favipiravir and Warfarin: A Case Series

“…7 This interaction was first confirmed by a case report whose patient was treated with favipiravir. 11 In that case report, INR increased from 1.43 to 4.63 within 4 days with the observable INR changes within 1 day after the concurrent use of warfarin and favipiravir. The onset of the interaction found in our study was also 4 days with observable changes on day 1 (case 2).…”

“…7 Together with the narrow therapeutic and long-term usage characteristics of warfarin, DDIs from favipiravir and warfarin are important, especially in Thai patients who require long-term anticoagulant therapy, for example, those with atrial fibrillation (AF), venous thromboembolism (VTE), and mechanical valve replacement. 8,9 The current real-world data 10 and a case report 11 suggest that the warfarin and favipiravir interaction resulted in DDIs that elevate the international normalized ratio (INR). However, some necessary information including the onset and duration of the DDIs, which is important for the appropriate management and INR monitoring in patients who were concurrently treated with favipiravir and warfarin, is still insufficiently reported.…”