The Effectiveness and Safety of Favipiravir in COVID-19 Hospitalized Patients at Tertiary Referral Hospital, Bali, Indonesia

Herni Damayanti, I Gede K Sajinadiyasa, Hindun Wilda Risni, Rani Sauriasari

Abstract


COVID-19 is a major public health problem, with still questionable specific cure. Favipiravir is a COVID-19 antiviral that is potentially a therapy for COVID-19. This study aimed to analyze its effectivity and safety in moderate to critical hospitalized patients. This study was a retrospective cohort in a tertiary referral hospital in Denpasar City, Bali Province, Indonesia, from August 2020 to January 2021. There was a total of 192 patients; 96 in the favipiravir group and 96in the non-favipiravir group (remdesivir/oseltamivir). Effectivity was measured by assessing the clinical condition at the end of the isolation period of 14 days. The favipiravir group showed better clinical conditions than the non-favipiravir group (79.2% vs. 56.3%; adjusted RR = 2.196; 95% CI = 1.084 – 4.451; p-value= 0.029), seen from being free of fever and respiratory problems. Stratification analysis demonstrated that the clinical improvement was significantly differentin the severe/critical group in favor of favipiravir (RR = 1.573; 95% CI = 1.139-2.172). The most common non-serious adverse events (AE) found in the use offavipiravir were gastrointestinal disturbances (12.5%). In brief, favipiravir is effective in severe/critical cases, and less serious AE were found in its use. Appropriate treatment is expected to help in reducing the public health burden.

Keywords


COVID-19, effectivity, favipiravir, safety

Full Text:

PDF

References


 1. World Health Organization. COVID-19 weekly epidemiological update; 2019.

 2. Gebru AA, Birhanu T, Wendimu E, Ayalew AF, Mulat S, Abasimel HZ, et al. Global burden of COVID-19: situational analyis and review. Human Antibodies. 2021; 29 (2): 139–48.

 3. Khan JR, Awan N, Islam MM, Muurlink O. Healthcare capacity, health expenditure, and civil society as predictors of COVID-19 case fatalities: a global analysis. Frontiers in Public Health. 2020; 8: 347.

 4. Bjørner TB, Arnberg S. Terminal costs, improved life expectancy and future public health expenditure. International Journal of Health Care Finance and Economics. 2012; 12 (2): 129–43.

 5. Badan Pengawas Obat dan Makanan Republik Indonesia. Penetapan pedoman obat dalam penanganan Corona Virus Disease 2019 (COVID-2019). Jakarta (Indonesia); 2020.

 6. Furuta Y, Komeno T, Nakamura T. Favipiravir (T-705), a broad spectrum inhibitor of viral RNA polymerase. Proceedings of the Japan Academy. Series B, Physical and Biological Sciences. 2017; 93 (7): 449–63.

 7. Sanders JM, Monogue ML, Jodlowski TZ, Cutrell JB. Pharmacologic treatments for Coronavirus Disease 2019 (COVID-19): a review. JAMA. 2020; 323 (18): 1824–36.

 8. Cai Q, Yang M, Liu D, Chen J, Shu D, Xia J, et al. Experimental treatment with favipiravir for COVID-19: an open-label control study. Engineering (Beijing, China). 2020; 6 (10): 1192–8.

 9. Prasithsirikul W, Pongpirul K, Sakornsakolpat P, Burana C,Phutrakool P, Pongpirul WA. Adjunctive favipiravir for severe COVID-19: a retrospective observational study of the first 41 patientsin Thailand. Asian Biomedicine. 2020; 14(3): 107–10.

 10. Perhimpunan Dokter Spesialis Penyakit Dalam Indonesia. Pedoman tata laksana COVID-19 edisi 2 Agustus 2020. Jakarta (Indonesia); 2020.

 11. Badan Pengawas Obat Dan Makanan Republik Indonesia. Tingkatkan angka kesembuhan dan turunkan angka kematian pasien COVID-19, Badan POM terbitkan izin penggunaan dalam kondisi darurat obat favipiravir dan remdesivir. Siaran Pers. Jakarta, Indonesia; 2020.

 12. Badan Pengawas Obat dan Makanan & Japan International Cooperation Agency. Modul farmakovigilans untuk tenaga profesional kesehatan, proyek “ensuring drug and food safety.” Jakarta (Indonesia); 2020.

 13. Sastroasmoro S. Dasar-dasar metodologi penelitian edisi ke-4. 4thEdition. Jakarta (Indonesia): Sagung Seto. 2011 p. 359.

 14. Centers for Disease Control and Prevention. COVID-19 ending isolation and precautions for people with COVID-19: interim guidance key findings from transmission literature. 2021 p. 1–7.

 15. Groban L, Wang H, Sun X, Ahmad S, Ferrario CM. Is sex a determinant of COVID-19 infection? Truth or myth? Current Hypertension Reports. 2020; 22 (9): 62.

 16. Ahmad OB, Boschi-pinto C, Lopez AD. Age standardization of rates: a new WHO standard. GPE Discussion Paper Series; 2001.

 17. Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet (London, England). 2020; 395 (10229): 1054–62.

 18. Kementerian Kesehatan Republik Indonesia. Klasifikasi obesitas setelah pengukuran IMT; 2018.

 19.Pranata R, Lim MA, Yonas E, Vania R, Lukito AA, Siswanto BB, et al. Body mass index and outcome in patients with COVID-19: a dose–response meta-analysis. Diabetes & metabolism. 2021; 47 (2): 101178.

 20. Zaki N, Alashwal H, Ibrahim S. Association of hypertension, diabetes, stroke, cancer, kidney disease, and high-cholesterol with COVID-19 disease severity and fatality: a systematic review. Diabetes &Metabolic Syndrome. 2020; 14 (5): 1133–42.

 21. Muniyappa R, Gubbi S. COVID-19 pandemic, coronaviruses, and diabetes mellitus. American Journal of Physiology. Endocrinology and Metabolism. 2020; 318 (5): E736–41.

 22. Pranata R, Lim MA, Huang I, Raharjo SB, Lukito AA. Hypertension is associated with increased mortality and severity of disease in COVID-19 pneumonia: a systematic review, meta-analysis and meta-regression. Journal of the Renin-Angiotensin-Aldosterone System: JRAAS.2020; 21 (2): 147032032092689.

 23. Hafiz M, Icksan AG, Harlivasari AD, Aulia R, Susanti F, Eldinia L. Clinical, radiological features and outcome of COVID-19 patients in a secondary hospital in Jakarta, Indonesia. The Journal of Infection in Developing Countries. 2020; 14 (7): 750–7.

 24. Goyal A, Cardozo-Ojeda EF, Schiffer JT. Potency and timing of antiviral therapy as determinants of duration of SARS-CoV-2 shedding and intensity of inflammatory response. Science Advances. 2020; 6 (47):1–14.

 25. Lauer SA, Grantz KH, Bi Q, Jones FK, Zheng Q, Meredith HR, et al. The incubation period of Coronavirus Disease 2019 (COVID-19) from publicly reported confirmed cases: estimation and application. Annalsof internal medicine. 2020; 172 (9): 577–82.

 26. Kementerian Perencanaan Pembangunan Nasional/ Badan Perencanaan Pembangunan Nasional. Studi pembelajaran penanganan COVID-19 Indonesia. Jakarta (Indonesia); 2021.

 27. Kadri SM, Mattoo S, Brady AH, Petkovic M. Innovative solutions to the clinical challenges of COVID-19. In: Garg L, Chakraborty C, Mahmoudi S, Sohmen V.S. (eds) Healthcare informatics for fighting COVID-19 and future epidemics. EAI/Springer Innovations in Communication and Computing. Springer, Cham. 2022 p. 337–51.

 28. Udwadia ZF, Singh P, Barkate H, Patil S, Rangwala S, Pendse A, et al. Efficacy and safety of favipiravir, an oral RNA-dependent RNA polymerase inhibitor, in mild-to-moderate COVID-19: a randomized, comparative, open-label, multicenter, phase 3 clinical trial. International Journal of Infectious Diseases: IJID: official publication of the International Society for Infectious Diseases. 2021; 103: 62–71.

 29. Solaymani-Dodaran M, Ghanei M, Bagheri M, Qazvini A, Vahedi E, Hassan Saadat S, et al. Safety and efficacy of favipiravir in moderateto severe SARS-CoV-2 pneumonia. International Immunopharmacology. 2021; 95: 107522.

 30. Shrestha DB, Budhathoki P, Khadka S, Shah PB, Pokharel N, Rashmi P. Favipiravir versus other antiviral or standard of care for COVID-19 treatment: a rapid systematic review and meta-analysis. Virology Journal. 2020; 17 (1): 141.

 31. Liu J, Zhang S, Wu Z, Shang Y, Dong X, Li G, et al. Clinical outcomes of COVID-19 in Wuhan, China: a large cohort study. Annals of Intensive Care. 2020; 10 (1): 99.

 32. Frediansyah A, Tiwari R, Sharun K, Dhama K, Harapan H. Antivirals for COVID-19: a critical review. Clinical Epidemiology and Global Health. 2021; 9: 90–8.

 33. Instiaty, Darmayani IGAAPS, Marzuki JE, Angelia F, William, Siane A, et al. Antiviral treatment of COVID-19: a clinical pharmacology narrative review. Medical journal of Indonesia. 2020; 29 (3): 332–35.

 34. World Health Organization Solidarity Trial Consortium. Repurposed antiviral drugs for Covid-19 — Interim WHO solidarity trial results.The New England Journal of Medicine. 2021; 384 (6): 497–511.

 35. Zhang J, Wu J, Sun X, Xue H, Shao J, Cai W, et al. Association of hypertension with the severity and fatality of SARS-CoV-2 infection: a meta-analysis. Epidemiology and Infection. 2020; 148: e106.

 36. Lim S, Bae JH, Kwon HS, Nauck MA. COVID-19 and diabetes mellitus: from pathophysiology to clinical management. Nature Reviews. Endocrinology. 2021; 17(1): 11–30.

 37. Tan L, Kang X, Ji X, Li G, Wang Q, Li Y, et al. Validation of predictors of disease severity and outcomes in COVID-19 patients: a descriptive and retrospective study. Med (New York, N.Y.). 2020; 1 (1): 128-138.e3.

 38. Tjendra Y, Al Mana AF, Espejo AP, Akgun Y, Millan NC, Gomez-Fernandez C, et al. Predicting disease severity and outcome in COVID-19 patients: a review of multiple biomarkers. Archives of Pathology & Laboratory Medicine. 2020; 144 (12): 1465–74.

 39. Yamamura H, Matsuura H, Nakagawa J, Fukuoka H, Domi H, Chujoh S. Effect of favipiravir and an anti-inflammatory strategy for COVID-19. Critical Care (London, England). 2020; 24(1): 413.

 40. Hassanipour S, Arab-Zozani M, Amani B, Heidarzad F, Fathalipour M, Martinez-de-Hoyo R. The efficacy and safety of favipiravir in treatment of COVID-19: a systematic review and meta-analysis of clinical trials. Scientific Reports. 2021; 11 (1): 11022.

 41. Pilkington V, Pepperrell T, Hill A. A review of the safety of favipiravir– a potential treatment in the COVID-19 pandemic?. Journal of Virus Eradication. 2020; 6(2): 45–51.

 42. Wang D, Li Z, Liu Y. An overview of the safety, clinical application and antiviral research of the COVID-19 therapeutics. Journal of Infection and Public Health. 2020; 13 (10): 1405–14.

 43. Baj J, Karakuła-Juchnowicz H, Teresiński G, Buszewicz G, Ciesielka M, Sitarz E, et al. COVID-19: specific and non-specific clinical manifestations and symptoms: the current state of knowledge. Journal of Clinical Medicine. 2020; 9(6): 1753.

 44. Bohn MK, Hall A, Sepiashvili L, Jung B, Steele S, Adeli K. Pathophysiology of COVID-19: mechanisms underlying disease severity and progression. Physiology (Bethesda, Md.). 2020; 35 (5): 288–301.

 45. Gupta A, Madhavan M V., Sehgal K, Nair N, Mahajan S, Sehrawat TS, et al. Extrapulmonary manifestations of COVID-19. Nature Medicine. 2020; 26 (7): 1017–32.

 46. Dawoud DM, Soliman KY. Cost-effectiveness of antiviral treatments for pandemics and outbreaks of respiratory illnesses, including COVID-19: a systematic review of published economic evaluations. Value in Health : the Journal of the International Society for Pharmacoeconomics and Outcomes Research. 2020; 23 (11): 1409–1422.




DOI: http://dx.doi.org/10.21109/kesmas.v16i4.5433

Refbacks

  • There are currently no refbacks.