Incidence of adverse reaction of drugs used in COVID-19 management: a retrospective, observational study

BACKGROUND: An urgent need for coronavirus infectious disease (COVID-19) treatment has resulted in off-label drug use. Although previous studies had investigated the adverse drug reaction (ADR) of the medications for COVID-19 in their respective local settings, the safety profile in a Malaysian setting remains unknown. Our study aims to establish the incidence of ADR for drugs used in COVID-19 management in a Malaysian tertiary hospital.

METHODS: This retrospective observational study enrolled patients started on drugs for COVID-19 in Sungai Buloh Hospital from 1 March 2020 to 31 May 2020. The clinical staging of COVID-19 patients was decided by the treating physician in accordance with the Clinical Management of Confirmed COVID-19 Case in Adults (Annex 2E). Suspected ADRs were evaluated with a trigger tool of pre-defined laboratory values or the adverse events listed in the registered product insert. Causality assessment was conducted when an ADR was suspected using the World Health Organization-Uppsala Monitoring Centre (WHO-UMC) system, and only cases classified as certain, probable and possible ADR were considered. Data analysis was completed with descriptive, univariate and multivariate analysis.

RESULTS: The study (N = 1,080) identified 217 patients (20.1%) who experienced ADR, with 246 adverse events detected. Most events were related to the gastrointestinal (43.5%), hepatobiliary (36.2%) and cardiac (16.3%) systems. The most commonly suspected drugs were atazanavir (52.7%), chloroquine (36.8%) and lopinavir/ritonavir (34.6%). The independent risk factors of ADR were female (adjusted odds ratio (OR): 1.53; 95% CI 1.06-2.20; P = 0.024), diagnosis of COVID-19 stage 3 (adjusted OR: 2.58; 95% CI 1.20-5.55; P = 0.015) and stage 4 (adjusted OR: 4.17; 95% CI 1.79-9.73; P = 0.001), and the number of COVID-19 drugs (adjusted OR: 3.34; 95% CI 2.51-4.44; P