Journal of Tropical Diseases & Public Health

Favipiravir: Promising Therapy for COVID-19

Amit Kumar Das^* Shree Hospital and Maternity, Muzaffarpur, Bihar, India
^*Correspondence: Diabetologist. Amit Kumar Das, Shree Hospital and Maternity, Muzaffarpur, Bihar, India, Tel: +919433779961, Email:

Received: 17-Jul-2020 Published: 17-Aug-2020, DOI: 10.35248/2329-891X.20.8.356

Introduction

Severe acute respiratory syndrome coronavirus 2 (COVID-19 or 2019 Novel Coronavirus, named by WHO on February 11, 2020) is a respiratory pathogen which caused recent outbreak of coronavirus disease [1]. Across the globe to control the current outbreak and to reduce person to person transmission of COVID-19, drastic confinement measures have been implemented. But in realty COVID-19 still poses a fetal and serious public health threat all over the world despite those measures.

Mechanism of Action of Favipiravir

Favipiravir has broad-spectrum antiviral activity against RNA viruses of different virus families and developed in Japan in 2002 [2]. Favipiravir, also known as Avigan or T-705. Favipiravir is a pyrazine derivative that acts as an inhibitor of viral RNAdependent RNA polymerase and as a result causing chain termination and preventing RNA elongation in cell. However, for both teratogenicity and embryotoxicity in humans it is a mutagen and has potential. Against DNA viruses it has no activity [3]. Of note is that favipiravir shows anti-viral activities against other RNA viruses such as arenaviruses, bunyaviruses and filoviruses, all of which are known to cause fatal hemorrhagic fever. These unique anti-viral profiles will make favipiravir a potentially promising drug for specifically untreatable RNA viral infections [4] (Figure 1).

Figure 1. Mechanism of action of favipiravir (T‐705) against the virus. Favipiravir is incorporated into cells and converted to favipiravir ibofuranosyl‐5′-triphosphate (favipiravir-RTP) by host cells. The triphosphate form, favipiravir-RTP, inhibits the activity of RNA dependent RNA polymerase (RdRp) of RNA viruses. AO: Aldehyde Oxidase; RMP: Ribosyl Monophosphate.

Clinical Benefit of Favipiravir

Cai et al. had conducted an open-label, control, non-randomised trial to evaluate the effects of favipiravir versus lopinavir-ritonavir for the treatment of COVID-19 in the isolation ward of the national clinical research centre for infectious diseases in Shenzhen, China [5]. In this trial, on day 1 dose of 1600 mg twice-daily favipiravir was used and on days 2-14 favipiravir dose was 600 mg twice-daily. On contrast in same study 400 mg lopinavir and 100 mg ritonavir twice-daily was the dose of lopinavir-ritonavir. Both favipiravir and lopinavir-ritonavir were continued until 14 days had passed or until viral clearance was confirmed. In favipiravir (experimental) arm 35 patients were included and it was 45 in other arm of the study. A higher improvement rate in chest imaging and a faster viral clearance was observed in favipiravir arm compared to those in the control arm. No treatment discontinuation in favipiravir arm and much less adverse events observed as compared to control arm.

In a recent clinical trial favipiravir was compare with arbidol in 200 patients receiving conventional therapy. In this trial 120 patients were assigned to receive favipiravir where as other 120 were assign to receive arbidol for 10 days. Both pyrexia by 1.70 days (p<0.0001) and cough by 1.75 days (p<0.0001) were reduced or relieved by favipiravir as compare to other control arm [6].

A case reported in homepage of Japanese Association for Infectious Diseases indicate that COVID-19 pneumonia was alleviated by favipiravir [7].

In February 2020, in Shenzhen, an observational study, showed a significantly faster mean time to viral clearance of favipiravir than lopinavir/ritonavir {4 days vs 11 days (p<0.001)} [8]. In another RCT study than umefenovir favipiravir treatment led to a significantly greater recovery rate in non-critical COVID-19 patients (71.4% vs 55.9% {p<0.05}) [9]

Following Table 1 demonstrate the upcoming registered trial with favipiravir in recent future.

Table 1: Registered clinical trials with favipiravir for the treatment of COVID-19.

Side Effect

Using an elevated dosing regimen of favipiravir, elevated liver enzyme levels and lipemia (abnormally high blood concentration of emulsified fat) and transient thrombocytopenia (abnormally low levels of platelets) was found in an animal study of Lassa virus infection [10]. Favipiravir may cause corrected QT (QTc) interval prolongation when administered at high doses as reported by Chinello et al. [11]. If pregnancy is confirmed or suspected favipiravir administration should be avoided in women as it is known to be teratogenic [12,13]. Favipiravir and paracetamol might have a drug interaction as suggested in one in vitro study [14]. In patients concomitantly taking favipiravir maximum daily paracetamol dosage to 3 g (rather than the conventional 4 g) to avoid clinically significant interaction between these two drugs as suggested by Zhao et al. [14]. Exposure of cephalexin, flucloxacillin and penicillin may potentially increase by favipiravir [15].

There is evidence to support the safety and tolerability of favipiravir in short-term use. However, more evidence is needed to assess the longer-term effects of treatment. Given the limits of the evidence and the remaining specific safety concerns, caution is warranted in the widespread use of favipiravir against pandemic COVID-19.

Conclusion

Existing studies has confirmed the clinical effectiveness of favipiravir to treat mild to moderate COVID-19 patients. Given the limitations of the evidence and unresolved efficacy and safety concerns, caution is warranted in the widespread use of favipiravir against pandemic COVID-19. Rather an overview of several relevant publications in this area of practice this review does not intend to be a comprehensive collation of all relevant literature following a basic literature search strategy.

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