Clinical usefulness of favipiravir in moderate COVID-19 patients: Indian real-world experience

Introduction: Favipiravir, a broad-spectrum antiviral agent, acts by inhibiting RNA-dependent RNA polymerase It is approved in India in the management of mild-moderate COVID-19 It has shown potent in vitro activity against SARS-CoV-2 It has a wide therapeutic safety margin indicated by a wide CC50/EC50 ratio for a high dose It has shown promising results in clinical studies conducted in China, Russia, Japan, and India Treatment guidelines from many countries and some states from India have included favipiravir in the treatment protocol A recently published phase III trial on favipiravir in India has shown early clinical resolution and acceptable safety in mild-moderate COVID-19 infection Objectives: The primary objective of the study was to evaluate the effectiveness of favipiravir in moderate COVID-19 patients, while the secondary objective was to determine the safety of favipiravir Materials and methods: We retrospectively analyzed medical records of favipiravir-treated COVID-19 cases from 3 centers to capture key details of moderate COVID-19 patients including medical history, symptoms, supportive treatment, and clinical outcome The protocol of the study was approved by Independent Ethics Committee Results: Data from medical records of 193 patients was available for analysis, including 54 patients of moderate severity The mean age was 59 94 ± 13 18 years 58 92% of the patients were male Hypertension (78 57%) and diabetes (55 35%) were the two most prevalent comorbidities Majority (85 71%) of patients had at least one comorbidity, while 66 07% had ≥2 comorbidities Mean SpO2 was 92 83 ± 1 88% with a median of 93% (90-98) The most common clinical features were fever (87 5%), cough (80 35%), dyspnoea (57 14%) and myalgia (48 12%) The mean CRP was 65 58 ± 34 74 with a median of 57 85 (1 20 to 151) and the mean d-Dimer was 1082 95 ± 1129 7 with a median of 815 (156-7435) Favipiravir has been used for an average duration of 12 30 ± 3 99 days, with median duration of 14 days (1-14 days) The rate of clinical improvement on days 3, 5, 7 and 10 was 30 35%, 75%, 89 29% and 96 42% Fever and dyspnoea were fully resolved by day 7 in all enrolled patients, while myalgia was resolved by day 10 in all patients and cough was resolved by day 10 in 97 77% of patients Corticosteroid was used in 37 5% patients Oxygen requirements on days 3, 5, 7 and 10 were 28 57%, 14 28%, 8 92% and 7 14% patients respectively Progression of the disease was seen in 10 71% of cases Overall favipiravir was well tolerated with few commonly reported adverse events like diarrhoea and nausea, which does not require drug discontinuation 91 07% patients and physician rated favipiravir as good or very good on global assessment scale Discussions: An open-labeled nonrandomized study1 from China compared the effect of favipiravir (day 1: 1,600 mg twice daily;days 2-14: 600 mg twice daily) vs lopinavir/ritonavir (day 1-14: 400/100 twice daily) in the treatment of COVID-19 Compared with the lopinavir/ritonavir arm, however, patients in the favipiravir arm showed a statistically significant shorter median length of time to viral clearance (4 vs 11 days, p 90% of cases, favipiravir was administered at a dose of 1,800 mg orally on ay 1 followed by 800 mg twice daily on subsequent days The median duration of therapy was 11 days Rates of clinical improvement at 7 and 14 days were 73 8 and 87 8%, 66 6 and 84 5%, and 40 1 and 60 3% for mild, moderate, and severe disease, respectively Thus, the vast majority of patients with mild and moderate disease recovered from the illness Conclusion: Approximately 90% clinical resolution rate in moderate COVID-19 patients in real-world settings supports its role in the management of hospitalized patients Reduction in the oxygen requirement highlights its protective role against disease progression Overall favipiravir was found to be effective and safe in the management of moderate COVID-19