Background: Repurposing broad-spectrum antivirals is an immediate treatment opportunity for 2019 coronavirus disease (COVID-19) Favipiravir is an antiviral previously indicated for influenza and Ebola, which has shown some promise in early trials for treatment of COVID-19 We aim to review existing favipiravir safety evidence, which is vital to informing the potential future use of favipiravir in COVID-19 Methods: A search was conducted across EMBASE and MEDLINE databases, supplemented by relevant grey-literature and ClinicalTrials gov All studies assessing the use of favipiravir in humans by 27 March 2020 were considered for inclusion Further analysis of available safety data from phase 2 and 3 studies was undertaken Data extracted were adverse events (AEs) grade 1-4, serious AEs and discontinuation for AEs Specific AEs of interest highlighted in early-phase studies, including gastrointestinal AEs and hyperuricaemia, were also examined Results: Twenty-nine studies were identified as potential sources of evidence of the clinical safety of favipiravir Six were phase 2 and 3 studies reporting relevant safety data for statistical comparison, representing a total of 4299 participants, an estimated 175 person-years-of-follow-up (PYFU) Comparator drugs were oseltamivir, umifenovir, lopinavir/ritonavir or placebo Study follow-up was between 5 and 21 days The proportions of grade 1-4 AEs on favipiravir was 28 2% vs 28 4% (P = n s ) in the comparison arms The proportion of discontinuations due to AEs on favipiravir was 1 1% vs 1 2% (P = n s ) in the comparison arms For serious AEs the proportion was 0 4% in both arms (P = n s ) There were significantly fewer gastrointestinal AEs occurring on favipiravir vs comparators [8 7% vs 11 5%;P = 0 003] Favipiravir showed significantly more uric acid elevations than comparators [5 8% vs 1 3%;P&lt;0 0001] Conclusions: Favipiravir demonstrates a favourable safety profile regarding total and serious AEs However, safety concerns remain: hyperuricaemia, teratogenicity and QTc prolongation have not yet been adequately studied Favipiravir may be safe and tolerable in short-term use, but more evidence is needed to assess the longer-term effects of treatment Given the limitations of the evidence and unresolved safety concerns, caution is warranted in the widespread use of favipiravir against pandemic COVID-19
A review of the safety of favipiravir - a potential treatment in the COVID-19 pandemic?