Abstract: International Journal of General Medicine Dovepress open access to scientific and medical research International Journal of General Medicine For personal use only. Open Access Full Text Article ORIGINAL RESEARCH Effectiveness and Safety of Favipiravir Compared to Hydroxychloroquine for Management of Covid-19: A Retrospective Study Musim Alotaibi 1,2 Ahmed Ali 1,3 Duaa Bakhshwin 4 Yasser Alatawi 5 Sultan Alotaibi 6 Abdullah Alhifany Badr Alharthi 2 Nasser Alharthi 2 Awatef Alyazidi 2 Yasmeen Alharthi 2 Aziza Alrafiah 8 7 1 Department of Pharmacology, King Abdulaziz University, Jeddah City, Kingdom of Saudi Arabia; 2Department of Pharmacy, King Faisal Medical Complex, Taif City, Kingdom of Saudi Arabia; 3 Department of Pharmaceutics, Assiut University, Assiut City, Egypt; 4 Department of Pharmacotherapy and Outcomes Science, King Abdulaziz University, Jeddah City, Kingdom of Saudi Arabia; 5Department of Pharmacy Practice, University of Tabuk, Tabuk City, Kingdom of Saudi Arabia; 6Department of Pharmacy, King Abdul-Aziz Medical, Jeddah City, Kingdom of Saudi Arabia; 7 Department of Clinical Pharmacy College of Pharmacy, Umm Al-Qura University, Makkah, Kingdom of Saudi Arabia; 8Department of Medical Laboratory Technology, King Abdulaziz University, Jeddah City, Kingdom of Saudi Arabia Correspondence: Aziza Alrafiah P.O Box 80200, Jeddah, 21589, Kingdom of Saudi Arabia Tel +966 126401000 Ext. 23495 Fax +966 126401000 Ext. 21686 Email aalrafiah@kau.edu.sa Background: Coronavirus disease (COVID-19) is an infectious disease due to SARS-COV -2. Patients with risk factors are vulnerable to severe morbidity and mortality. Favipiravir (FPV) and hydroxychloroquine (HCQ) are considered possible COVID-19 treatments. Objective: To investigate the effectiveness and safety of FPV compared to HCQ in patients with COVID-19 as the standard of care approved by the national protocol there. Methods: This is a retrospective cohort study on patients with COVID-19 who were administered either FPV or HCQ at King Faisal Medical Complex, Taif, Saudi Arabia, from June 2020 to August 2020. Results: In total, 508 patients were included in the analysis. Patients were categorized into three groups by medication. Patients enrolled in this study were 244 (55.8%) on FPV, 193 (44.2%) on HCQ and 71 (13.81%) on neither medication. Patients who received FPV had higher age and greater comorbidity. Most of the patients were discharged on day 14 (n = 303, 59.6%), 26 (36.6%) in neither med, 154 (63.1%) in FPV and 123 (63.7%) in HCQ groups with significant difference between groups (P < 0.0001). Mortality rate was 8.2% (n = 20) in FPV and 7.3% (n = 14) in HCQ groups with significant difference between groups (P = 0.048). Regarding drug safety, 19.7% of patients treated with FPV vs 7.8% HCQ have adverse effects with significant difference between groups (P < 0.0001). Most of the side effects were increase ALT and AST. Meanwhile, prolonged Q-T interval was reported only in the HCQ group (2.6%). From Cox regression modeling, only mechanical ventilation due to Covid 19 was predictive for mortality (HR: 16.598, 95% CI: 7.095– 38.828, P < 0.0001). Meanwhile, there was no significant difference in the prediction of discharge of FPV (vs HCQ) (HR: 0.933, 95% CI: 0.729–1.195, P = 0.5843), predictors of mortality were HCQ (vs FPV) (HR: 2.3, 95% CI: 0.994–5.487, P = 0.0518). Kaplan–Meier survival..