954: Favipiravir update

1. Currently under investigation for use in the treatment of coronavirus disease 2019 (COVID-19)

2. At this time, safety and efficacy have not been established.

3. Coronavirus disease 2019 (COVID-19) (off-label use): Oral: Optimal dose and duration unknown, limited data available; 1,600 mg twice daily on day 1, followed by 600 mg twice daily for a total duration of 7 to 14 days (Cai 2020; NIH 2020a).

4. Another clinical trial is using a dose of 2.4 g every 8 hours for 2 doses, followed by a dose of 1.2 g 8 hours later on day 1, followed by 1.2 g twice daily for a total duration of 7 to 10 days (NIH 2020b).

5. Favipiravir is an RNA polymerase inhibitor

6. Available in some Asian countries for treatment of influenza

7. In a study of patients with non-severe disease (including oxygen saturation >93 percent), use of favipiravir was associated with faster rates of viral clearance (median time to clearance 4 versus 11 days) and more frequent radiographic improvement (in 91 versus 62 percent by day 14) compared with lopinavir-ritonavir. However, other therapies were administered in this non-randomized, open-label study, so the results should be interpreted with caution given potential confounders. [Engineering. 2020; ]

8. Favipiravir selectively inhibits RNA polymerase, which is necessary for viral replication.

9. Japan has commenced with a phase 3 clinical trial. In the United States, a phase 2 trial will enroll approximately 50 patients with COVID-19, in collaboration with Brigham and Women's Hospital, Massachusetts General Hospital, and the University of Massachusetts Medical School. In India, a phase 3 trial combining 2 antiviral agents, favipiravir and umifenovir, started in May 2020.

10. Adverse Reactions

Frequency not defined:

Gastrointestinal: Decreased appetite (Cai 2020), diarrhea (Cai 2020; Hayden 2019; Sanders 2020), nausea, vomiting

Endocrine & metabolic: Hyperuricemia (Chen 2020; Hayden 2019; Sanders 2020)

Hematologic & oncologic: Decreased neutrophils (Hayden 2019; Sanders 2020)

Hepatic: Hepatic injury (Cai 2020), increased serum transaminases (Hayden 2019; Sanders 2020)

Metabolism/Transport Effects

Inhibits CYP2C8 (weak)

Drug Interactions

Influenza Virus Vaccine (Live/Attenuated): Antiviral Agents (Influenza A and B) may diminish the therapeutic effect of Influenza Virus Vaccine (Live/Attenuated). Management: Avoid anti-influenza antivirals during the period beginning 48 hours prior to and ending 2 weeks after live influenza virus vaccine administration. Risk D: Consider therapy modification

Pyrazinamide: Favipiravir may enhance the adverse/toxic effect of Pyrazinamide. Specifically, the risk for increased uric acid concentrations may be increased. Risk C: Monitor therapy

Repaglinide: CYP2C8 Inhibitors (Weak) may increase the serum concentration of Repaglinide. Risk C: Monitor therapy

Reproductive Considerations

Favipiravir is not approved for use in the United States. Based on data from animal reproduction studies, use is contraindicated for use in females who may become pregnant in countries where it is approved for the treatment of influenza.

Evaluate pregnancy status prior to use in females of reproductive potential. Females of reproductive potential should use effective contraception during therapy and for 1 week after the last favipiravir dose. Males with female partners of reproductive potential should use effective contraception during therapy and for 1 week after the last dose of favipiravir.

Pregnancy Considerations

Favipiravir is not approved for use in the United States. Based on data from animal reproduction studies, use is contraindicated in pregnant patients in countries where it is available for the treatment of influenza.

Favipiravir is under study for the treatment of coronavirus disease 2019 (COVID-19); however, pregnant patients were not included in the initial clinical trials (Cai 2020). The American College of Obstetricians and Gynecologists (ACOG) and the Society for Maternal-Fetal Medicine (SMFM) have developed an algorithm to aid practitioners in assessing and managing pregnant women with suspected or confirmed COVID-19 (https://www.acog.org/topics/covid-19; https://www.smfm.org/covid19). Interim guidance is also available from the CDC for pregnant women who are diagnosed with COVID-19 (https://www.cdc.gov/coronavirus/2019-ncov/hcp/inpatient-obstetric-healthcare-guidance.html).

Data collection to monitor maternal and infant outcomes following exposure to COVID-19 during pregnancy is ongoing. Health care providers are encouraged to enroll females exposed to COVID-19 during pregnancy in the Organization of Teratology Information Specialists (OTIS) pregnancy registry (877-311-8972; https://mothertobaby.org/join-study/) or the PRIORITY (Pregnancy CoRonavIrus Outcomes RegIsTrY) (415-754-3729, https://priority.ucsf.edu/).

Breast-Feeding Considerations

It is not known if favipiravir is present in breast milk.

Based on data from animal studies, breastfeeding is contraindicated during favipiravir therapy (Hayden 2019).

Favipiravir is under study for the treatment of coronavirus disease 2019 (COVID-19); however, lactating women were not included in the initial clinical trials (Cai 2020). Interim guidance is available from the Centers for Disease Control and Prevention for lactating women who are diagnosed with COVID-19 (https://www.cdc.gov/coronavirus/2019-ncov/hcp/inpatient-obstetric-healthcare-guidance.html). Information related to COVID-19 and breastfeeding is also available from the World Health Organization (https://www.who.int/docs/default-source/maternal-health/faqs-breastfeeding-and-covid-19.pdf?sfvrsn=d839e6c0_1).

Monday, June 22, 2020

131 CMAAO CORONA FACTS and MYTH BUSTER FAVIPIRAVIR now in India