CYFAVIR-400

Mechanism of Action

The mechanism of its actions is related to the selective inhibition of viral RNA-dependent RNA polymerase. The mechanism of action of favipiravir is novel compared to existing influenza antivirals that primarily prevent entry and exit of the virus from cells. The active favipiravir-RTP selectively inhibits RNA polymerase and prevents replication of the viral genome.  Some studies have shown that when favipiravir-RTP is incorporated into a nascent RNA strand, it prevents RNA strand elongation and viral proliferation. It have also been found that the presence of purine analogs can reduce favipiravir’s antiviral activity, suggesting competition between favipiravir-RTP and purine nucleosides for RdRp binding.

Although favipiravir was originally developed to treat influenza, the RdRp catalytic domain (favipiravir’s primary target), is expected to be similar for other RNA viruses This conserved RdRp catalytic domain contributes to favipiravir’s broad-spectrum coverage.

PharmacoKinetics

Absorption

The bioavailability of favipiravir is almost complete at 97.6%. The mean Cmax for the recommended dosing schedule of favipiravir is 51.5 ug/mL.

Volume of distribution

The apparent volume of distribution of favipiravir is 15 – 20 L.

Protein binding

Favipiravir is 54% plasma protein-bound. Of this fraction, 65% is bound to serum albumin and 6.5% is bound to ɑ1-acid glycoprotein.

Metabolism

Favipiravir is extensively metabolized with metabolites excreted mainly in the urine. The antiviral undergoes hydroxylation primarily by aldehyde oxidase and to a lesser extent by xanthine oxidase to the inactive metabolite, T705M1.

Route of elimination 

Favipiravir’s metabolites are predominantly renally cleared. 

Adverse Reactions

Favipiravir may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:

• Shock
• Anaphylaxis
• Pneumonia
• Hepatitis fulminant
• Hepatic dysfunction
• Jaundice
• Toxic epidermal necrolysis
• Oculomucocutaneous syndrome (Stevens-Johnson syndrome)
• Acute kidney injury
• Neurological and psychiatric symptoms (consciousness disturbed, abnormal behavior, deliria, hallucination, delusion, convulsion)
• Colitis haemorrhagic.

Indications

Favipiravir is indicated for novel or re-emerging influenza virus infections (limited to cases in which other anti-influenza virus agents are not effective or insufficiently effective). It has also been approved for treatment of mild to moderate Covid-19 cases.

Drug Interactions

Precaution are to be used while administrating favipiravir with below mentioned drugs.

• Pyrazinamide : Blood uric acid level increases
• Repaglinide: Blood level of Repaglinide may increase causing hypoglycemia.
• Theophylline : Blood level of Favipiravir may increase, and adverse reactions to Favipiravir may occur
• Famciclovir , Sulindac : Efficacy of these drugs may be reduced

Precautions

Precaution are to be used while administrating favipiravir with below mentioned drugs.

• Pyrazinamide : Blood uric acid level increases
• Repaglinide: Blood level of Repaglinide may increase causing hypoglycemia.
• Theophylline : Blood level of Favipiravir may increase, and adverse reactions to Favipiravir may occur
• Famciclovir , Sulindac : Efficacy of these drugs may be reduced

Dosage

• For Mild to moderate COVID-19 (Under restricted emergency use in India) – The recommended dose of Favipiravir for adults (>18 years) is loading dose of 3,600 mg (1,800 mg BID) on day 1, followed by 1,600 mg per day (800 mg BID) From day 2 up to maximum of day 14.
• For Novel/ emerging Influenza Infection – The usual dosage of Favipiravir for adults is 1600 mg orally twice daily for 1 day followed by 600 mg orally twice daily for 4 days. The total administration period should be 5 days.

Storage

Do not store above 30°C.
Store in the original package in order to protect from moisture.
Keep all medications away from children and pets.

Overdose

Patients who ingest more than the recommended dosage should be closely monitored for myelosuppression and given appropriate supportive treatment.

Contraindications

Favipiravir is contraindicated in patients who are hypersensitive to the active substance favipiravir or to any of the excipients, severe renal or hepatic impairment, women known or suspected to be pregnant, and lactating women.