Use Of Favipiravir In COVID-19

Favipiravir is an oral antiviral drug. Currently, it is in the trial phase for the treatment of COVID-19. It is also known as Fapilavir & Favilavir. It is an approved antiviral drug for the treatment of influenza in Japan in2014. It is a combined form of pyrazines and a primary carboxamide i.e. pyrazine carboxamide. It is available in the market under the name of Avigan & Abigan.

It inhibits the enzyme named RNA dependent RNA polymerase (RdRp). It was discovered by Toyama Chemical Co. Ltd through screening antiviral activity against influenza virus. Favipiravir is also used in the treatment of other viruses such as Ebola virus and Lassa virus.

Japan started phase-3 clinical trial while the US begins with a phase-2 clinical trial with approximately 50 patients of COVID-19. India also initiates phase-3 clinical trial on Favipiravir in combination with Umifenovir in May 2020 for the treatment of COVID-19. According to some sources now In India Drugs Controller General of India (DCGI) approved Favipiravir for mild to the moderate treatment of COVID-19 under the brand name of fabriflu manufactured by Glenmark Pharmaceutical Ltd.

Chemistry of Favipiravir

Chemical Name: -(T-705; 6-fluoro-3-hydroxy-2-pyrazinecarboxamide) 

Molecular Formula: – C₅H₄FN₃O₂

Structure: –

How Favipiravir Works/ Mechanism of Action

It inhibits viral genome replication in the middle of the viral proliferation cycle. Favipiravir is a prodrug. it means, it will become an active form after incorporated in cell. And the active of Favipiravir is Favipiravir-RTP (ribofuranosyl-5’-triphosphate).

Favipiravir prevents viral transcription and replication by binding and inhibiting RNA dependent RNA polymerase (RdRP). According to some studies, purine analogs somehow reduce antiviral activity.

Pharmacokinetic Data (Absorption, Distribution, Metabolism, Excretion)

• It shows about 97.6% bioavailability and also causes inhibition of Aldehyde Oxidase when given at higher or multiple doses.
• Having the 15-20Ltr volume of distribution & about 54% plasma protein-bound.
• Metabolize hepatically by aldehyde oxidase and xanthine oxidase (partially). And excreted by the urine.
• Having Half-life of approximately 2-5hrs.

Uses

• Mainly used as an anti-influenza agent
• Used in the treatment of novel influenza-like Ebola virus, Lassa virus
• It is also used against yellow fever virus, mouth disease virus as well as flaviviruses, arenavirus, and bunyavirus.
• Currently, there are many agencies doing clinical trials to treat coronavirus. So, after a successful trial. It can be used in the novel coronavirus.  

Side Effects

• Reduced body weight
• Decreased locomotion activity
• Vomiting
• Teratogenicity
• Decreased WBC, neutrophil and platelets count
• Increase blood uric acid level
• Diarrhea
• Shock anaphylaxis.
• Hepatitis
• It can’t be given to pregnant women. It may affect the child inside the womb.

Drug Interaction

• It decreases the metabolism of warfarin drug
• It decreases the excretion of acyclovir and allopurinol
• It may also decrease excretion rate of acetyldigoxin which further results in higher serum level

Recent works on Favipiravir

Glenmark pharmaceutical Ltd. First Indian company who approached Drugs Controller General of India (DCGI) for the marketing and manufacturing of Favipiravir for the treatment mild to moderate COVID-19.

Glenmark developed an active pharmaceutical ingredient (API) of Favipiravir through its own research and development team. Favipiravir provides a rapid reduction in viral load and shows up to 88% clinical improvement in COVID-19 cases.

According to some sources, Glenmark undergoes a phase-3 clinical trial for approximately 150 COVID affected patients. In which about 10 private and government are used. The data from these trials is helpful for the management and treatment of COVID-19. This study will be done by July or August of 2020