PMID- 32405421
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220414
IS  - 2055-6640 (Print)
IS  - 2055-6659 (Electronic)
IS  - 2055-6640 (Linking)
VI  - 6
IP  - 2
DP  - 2020 Apr 30
TI  - A review of the safety of favipiravir - a potential treatment in the COVID-19 
      pandemic?
PG  - 45-51
AB  - 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<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.
CI  - (c) 2020 The Authors. Journal of Virus Eradication published by Mediscript.
FAU - Pilkington, Victoria
AU  - Pilkington V
AD  - Faculty of Medicine, Imperial College London, London, UK.
AD  - MetaVirology LTD, London, UK.
FAU - Pepperrell, Toby
AU  - Pepperrell T
AD  - Faculty of Medicine, Imperial College London, London, UK.
AD  - MetaVirology LTD, London, UK.
FAU - Hill, Andrew
AU  - Hill A
AD  - MetaVirology LTD, London, UK.
AD  - Department of Pharmacology and Therapeutics, University of Liverpool, Liverpool, 
      UK.
LA  - eng
PT  - Editorial
DEP - 20200430
PL  - England
TA  - J Virus Erad
JT  - Journal of virus eradication
JID - 101654142
PMC - PMC7331506
EDAT- 2020/05/15 06:00
MHDA- 2020/05/15 06:01
PMCR- 2020/04/30
CRDT- 2020/05/15 06:00
PHST- 2020/05/15 06:00 [entrez]
PHST- 2020/05/15 06:00 [pubmed]
PHST- 2020/05/15 06:01 [medline]
PHST- 2020/04/30 00:00 [pmc-release]
AID - 10.1016/S2055-6640(20)30016-9 [doi]
PST - epublish
SO  - J Virus Erad. 2020 Apr 30;6(2):45-51. doi: 10.1016/S2055-6640(20)30016-9.