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What is known and objective Favipiravir is a promising treatment candidate for managing coronavirus disease 2019 (COVID‐19). 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., It is important to evaluate the drug–drug interactions between the limited antiviral drugs used in COVID‐19 and the drugs used to manage common comorbidities. We report a case of elevated anticoagulant action i.e., international normalized ratio (INR), when favipiravir and warfarin were used concomitantly in a patient with COVID‐19.

Graphical abstract, Highlights • The contents of glabridin and medical component glycyrrhizin were analyzed in herbal medicines and health foods containing licorice. • A small amount of glycyrrhizin was detected in some of health foods. • Estrogenic activity was detected in some of health food ingredients and health foods. • Antioxidant activity was detected in all the materials. • Hepatic CYP activity, liver and uterine weights in estrogen deficient mice are also valuable for the safety evaluation of estrogenic ingredients., Focusing on licorice, a highly used raw material in health foods, quantitative analysis of functional/medicinal components and a safety and functional evaluation was carried out for herbal medicines, health food ingredients, and so-called health foods. A functional component, glabridin, was detected in herbal medicines from Glycyrrhiza glabra and G. inflata, health food ingredients, and in commercially available health foods that contain licorice. Likewise, glycyrrhizin, a medicinal component, was detected in these sources, except in licorice oil extract. Estrogen activity in vitro was detected in some of the herbal medicines, health food ingredients, and in health foods containing licorice. In the in vivo study, liver weight in ovariectomized (OVX) mice treated with licorice oil extract was significantly higher than that in OVX and sham mice in a dose dependent manner. These results suggest that excessive intake of licorice oil extract from health foods should be avoided, even though these ingredients might be beneficial for medical use in order to maintain bone health in postmenopausal women. Measurement of hepatic cytochrome P-450 (CYP) activity, reproductive organ weight, and fat and bone mass in OVX mice was considered useful for evaluating the safety and efficacy of estrogenic health food ingredients derived from herbal medicines.

Aim: Resveratrol is a popular ingredient in dietary supplements. Some patients concomitantly use dietary supplements and medicines in Japan. In the present study, we determined whether trans-resveratrol and melinjo (Gnetum gnemon L.) seed extract (MSE), which contains resveratrol dimers, interacted with drugs using a mouse model. Methods: Male C57BL/6J mice were fed experimental diets containing 0.005%, 0.05%, or 0.5% (w/w) trans-resveratrol or MSE for 1 or 12 weeks. The expression of liver cytochrome P-450 (CYP) mRNA and activity of liver microsomal CYP were measured. To determine the influence of resveratrol or MSE on drug efficacy, the anticoagulant activity of warfarin was examined in mice that were fed diets containing trans-resveratrol or MSE for 12 weeks. Results: When the mice were fed experimental diets for 1 week, none of the doses of trans-resveratrol and MSE affected body weight, liver weight, or plasma AST and ALT levels. Trans-resveratrol also did not affect CYP1A1, CYP1A2, CYP2C, or CYP3A activities. In contrast, 0.5% MSE slightly increased CYP1A1 activity. When the mice were fed experimental diets for 12 weeks, 0.05% trans-resveratrol increased CYP1A1, CYP2C, and CYP3A activities, whereas 0.5% MSE suppressed CYP3A activity. Under these conditions, 0.5% trans-resveratrol enhanced the anticoagulant activity of warfarin, although CYP2C activity increased. However, MSE did not affect the anticoagulant activity of warfarin. Conclusion: The 0.05% trans-resveratrol did not interact with warfarin in a mouse model, whereas 0.5% trans-resveratrol may have enhanced the anticoagulant activity of warfarin.