Uric Acid Elevation by Favipiravir, an Antiviral Drug

Mishima, Eikan; Anzai, Naohiko; Miyazaki, Mariko; Abe, Takaaki

doi:10.1620/tjem.251.87

Cited by 78 publications

(65 citation statements)

References 16 publications

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“…However, sputum and blood cultures prior to initiation of empirical antibiotics failed to identify a competing bacterial cause, and the clinical course was not consistent with occult coinfection. Finally, our patient developed mild hyperuricemia, a known side effect of favipiravir, 13 and raising the possibility of a crystal arthropathy as a cause of symptoms. Careful synovial fluid analysis did not identify MSU crystals, which ruled out gouty arthritis.…”

Section: Discussionmentioning

confidence: 76%

Reactive arthritis after COVID-19 infection

et al. 2020

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Reactive arthritis (ReA) is typically preceded by sexually transmitted disease or gastrointestinal infection. An association has also been reported with bacterial and viral respiratory infections. Herein, we report the first case of ReA after the he severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This male patient is in his 50s who was admitted with COVID-19 pneumonia. On the second day of admission, SARS-CoV-2 PCR was positive from nasopharyngeal swab specimen. Despite starting standard dose of favipiravir, his respiratory condition deteriorated during hospitalisation. On the fourth hospital day, he developed acute respiratory distress syndrome and was intubated. On day 11, he was successfully extubated, subsequently completing a 14-day course of favipiravir. On day 21, 1 day after starting physical therapy, he developed acute bilateral arthritis in his ankles, with mild enthesitis in his right Achilles tendon, without rash, conjunctivitis, or preceding diarrhoea or urethritis. Arthrocentesis of his left ankle revealed mild inflammatory fluid without monosodium urate or calcium pyrophosphate crystals. Culture of synovial fluid was negative. Plain X-rays of his ankles and feet showed no erosive changes or enthesophytes. Tests for syphilis, HIV, anti-streptolysin O (ASO), Mycoplasma, Chlamydia pneumoniae, antinuclear antibody, rheumatoid factor, anticyclic citrullinated peptide antibody and Human Leukocyte Antigen-B27 (HLA-B27) were negative. Gonococcal and Chlamydia trachomatis urine PCR were also negative. He was diagnosed with ReA. Nonsteroidal Anti-Inflammatory Drug (NSAID)s and intra-articular corticosteroid injection resulted in moderate improvement.

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Section: Discussionmentioning

confidence: 76%

Reactive arthritis after COVID-19 infection

et al. 2020

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“…The most common adverse event associated with favipiravir is hyperuricemia (4.79% according to the package insert), which is associated with inhibition of OAT1, OAT3 and URAT1 by this agent (11). The incidence was much higher in this trial at 84.1%, which is likely due to the higher dose used than is approved of for influenza in Japan (1,600 mg twice followed by 600 mg bid).…”

Section: Discussionmentioning

confidence: 79%

A Prospective, Randomized, Open-Label Trial of Early versus Late Favipiravir Therapy in Hospitalized Patients with COVID-19

Doi

Hibino

Hase

et al. 2020

Antimicrob Agents Chemother

204

205

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Favipiravir is an oral broad-spectrum inhibitor of viral RNA-dependent RNA polymerase that is approved for treatment of influenza in Japan. We conducted a prospective, randomized, open-label, multicenter trial of favipiravir for the treatment of COVID-19 at 25 hospitals across Japan. Eligible patients were adolescents and adults admitted with COVID-19 who were asymptomatic or mildly ill and had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Patients were randomly assigned at a 1:1 ratio to early or late favipiravir therapy (the same regimen starting on day 6 instead of day 1). The primary endpoint was viral clearance by day 6. The secondary endpoint was change in viral load by day 6. Exploratory endpoints included time to defervescence and resolution of symptoms. Eighty-nine patients were enrolled, of whom 69 were virologically evaluable. Viral clearance occurred within 6 days in 66.7% and 56.1% of the early and late treatment groups (adjusted hazard ratio [aHR], 1.42; 95% confidence interval [95% CI], 0.76–2.62). Of 30 patients who had a fever (≥37.5°C) on day 1, time to defervescence was 2.1 days and 3.2 days in the early and late treatment groups (aHR, 1.88; 95%CI, 0.81–4.35). During therapy, 84.1% developed transient hyperuricemia. Favipiravir did not significantly improve viral clearance as measured by RT-PCR by day 6 but was associated with numerical reduction in time to defervescence. Neither disease progression nor death occurred to any of the patients in either treatment group during the 28-day participation (Japan Registry of Clinical Trials jRCTs041190120).

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“…In addition, favipiravir increases uric acid levels in urine, which should be further investigated in patients with renal impairment; this is described in Mishima et al, 2020 [54]. In the phase III study, with a short treatment duration similar to use in COVID-19, adverse events in total occurred in 13/30 (43.4%) patients with mild renal impairment and in 110/363 (30.3%) patients with normal renal function.…”

Section: Renal Recommendationsmentioning

confidence: 95%