Elevated blood favipiravir levels are inversely associated with ferritin levels and induce the elevation of uric acid levels in COVID-19 treatment: A retrospective single-center study

Abstract

Introduction Measurement of blood Favipiravir (FPV) levels and accumulation of data in COVID-19 patients are critical for assessing FPV efficacy and safety. We performed a retrospective study based on measurements of blood levels of FPV and related factors in COVID-19 patients admitted to our hospital. Furthermore, we also investigated the association between blood FPV levels and uric acid level alterations before and after FPV administration. Methods We enrolled 27 COVID-19 patients who had received FPV treatment at Hokushin General Hospital from April 1 to December 31, 2020. Age, gender, COVID-19 severity, presence of comorbidities, and laboratory data for each subject were investigated to identify factors that correlate with blood FPV levels. Uric acid levels were measured before and after FPV administration and a difference between the levels ( i.e. , a change of uric acid level) was evaluated. Results When a significant univariate variable was input by the stepwise method and a combination of variables that maintained statistical superiority was searched, serum ferritin was the only factor that independently affected blood FPV level. Furthermore, in the high-FPV group (20 μg/mL or more), a significant increase in uric acid levels was observed after FPV administration. The increment value was significantly larger than that in the low-FPV group (less than 20 μg/mL). Conclusions Ferritin level was an important independent factor inversely affecting blood FPV level. Furthermore, a high blood FPV level induced the elevation of uric acid levels in COVID-19 treatment.

A systematic review and Bayesian network meta-analysis for comparative safety assessment of favipiravir interventions in hospitalized COVID-19 patients

“…In addition, due to the risk of teratogenicity and embryotoxicity associated with this chemical [40], the treatment of pregnant women and children requires more caution. It has also been suggested that blood favipiravir levels may be negatively correlated with blood ferritin levels in the treatment of patients with moderate to severe COVID-19 [41], and a clinical study has shown that favipiravir is ineffective in patients with elevated ferritin and that patients with high blood favipiravir levels frequently have elevated uric acid levels [42], implying that monitoring blood favipiravir levels is especially important when treating patients with COVID-19.…”

Evaluation of the clinical and quantitative performance of a practical HPLC-UV platform for in-hospital routine therapeutic drug monitoring of multiple drugs

“…We further demonstrated that the platform could be applied for the quantification of the serum levels of 15 different drugs (carbamazepine [CBZ], phenytoin [PHT], lamotrigine [LTG], disopyramide, flecainide, lidocaine, mexiletine, procainamide, propafenone, quinidine, sotalol, voriconazole [VRCZ], mycophenolic acid, imatinib, and pazopanib) with almost the same procedures and exactly the same HPLC-UV apparatus. Furthermore, the method was also applied to the clinical evaluation of the blood levels of favipiravir [ 12 , 13 ] and VRCZ [ 14 ] at different hospitals in Japan. However, with a few exceptions such as favipiravir and VRCZ, the method using the above platform is just beginning to be applied to the clinical evaluation of blood levels of other kinds of drugs during therapy in clinical practice.…”