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Brief Introduction of Favipiravir

Favipiravir (T-705; 6-fluoro-3-hydroxy-2-pyrazinecarboxamide) is an anti-viral agent that selectively and potently inhibits the RNA-dependent RNA polymerase (RdRp) of RNA viruses. Favipiravir undergoes an intracellular phosphoribosylation to be an active form, favipiravir-RTP (favipiravir ribofuranosyl-5B-triphos-phate), which is recognized as a substrate by RdRp, and inhibits the RNA polymerase activity. Since the catalytic domain of RdRp is conserved among various types of RNA viruses, this mechanism of action underpins a broader spectrum of anti-viral activities of favipiravir. Favipiravir is effective against a wide range of types and subtypes of influenza viruses, including strains resistant to existing anti-influenza drugs(including ones sensitive or resistant to marketed neuraminidase and M2 inhibitors). 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.


COVID-19

reported by the Science and Technology Daily

Currently, some countries have incorporated the marketed drug favipiravir into their treatment regimens. Clinical studies of favipiravir are being carried out in Shenzhen, Wuhan and other places in China.

The Third People’s Hospital of Shenzhen conducted a study on the efficacy and safety of favipiravir combined with interferon in the treatment of COVID-19,enrolled 80 patients(35 in favipiravir group[1600mg bid on day 1,600mg bid on day2-14.], 45 in control group[Lopinavir/ritonavir tablets 400mg/100mg bid]).

The result showed that,the median time of patients with undetectable viral RNA in favipiravir group was significantly shorter than that in the control group (4 days vs. 11 days). In terms of the improvement of the typical radiological finding on chest, the improvement rates of the favipiravir group and the control group were 91.43% and 62.22%, respectively. Meanwhile, The incidence of AE in favipiravir group was lower than that in the control group(11.43% vs. 55.56%). After controlling for potential confounding factors (age, onset time, fever),Favipiravir remains an independent factor for improved chest imaging and early virus clearance.

Recently, Zhongnan Hospital of Wuhan University led a randomized, open-controlled trial for farpiravir tablets in the treatment of COVID-19. Up to Mar 5th, a total of 88 patients had completed the 7-day course of clinical observation, including 44 patients in the favipiravir group and 44 patients in the positive control group. The results showed that the clinical recovery rate of the favipiravir group was better than that of the control group. The recovery rate of body temperature on the third day of treatment in favipiravir group was 81.8%, which was significantly higher than that of the control group (29.5%). The remission rate of cough on the 6th day of treatment in favipiravir group was 93.2%, which was significantly higher than that of the control group(68.2%). Continuous clinical observation and outcome analysis are still in progress recently. There will be totally 120 patients enrolled in both group.


DOSAGE AND ADMINISTRATION

The usual dosage of favipiravir for adults is 1600 mg orally twice daily for day 1 followed by 600 mg orally twice daily for the 6-9 days.

Tablets can be crushed and mixed with food and liquid.

 

WARNINGS

1. Since early embryonic deaths and teratogenicity have been observed in animal studies for favipiravir, do not administer the drug to women known or suspected to be pregnant.

2. When administering favipiravir to women of child-bearing potential, confirm a negative pregnancy test result before starting the treatment. Explain fully the risks and instruct thoroughly to use most effective contraceptive methods with her partner during and for 7 days after the end of the treatment. If pregnancy is suspected during the treatment, instruct to discontinue the treatment immediately and to consult a doctor.

3. Favipiravir is distributed in sperm. When administering the drug to male patients, explain fully the risks and instruct thoroughly to use most effective contraceptive methods in sexual intercourse during and for 7 days after the end of the treatment (men must wear a condom). In addition, instruct not to have sexual intercourse with pregnant women.

4. Prior to the treatment, explain thoroughly the efficacy and risks (including the risk of exposure to fetus) in writing to patients or their family members and obtain their written consent.

5. Examine carefully the necessity of favipiravir before use.

6. Patients with gout or a history of gout, and patients with hyperuricaemia (Blood uric acid level may increase, and symptoms may be aggravated.