Incidence of Adverse Drug Reactions in COVID‐19 Patients in China: An Active Monitoring Study by Hospital Pharmacovigilance System

Abstract

To evaluate the incidence, type, and risk factors associated with adverse drug reactions (ADRs) among patients with coronavirus disease 2019 (COVID‐19) by Hospital Pharmacovigilance System (CHPS). A retrospective analysis was performed on 217 patients with COVID‐19 admitted to the First Hospital of Changsha in China, from January 17, 2020, to February 29, 2020. The active monitoring model in CHPS was used to detect ADR signals of the hospital information system. The risk factors for the ADRs were classified using the World Health Organization‐Uppsala Monitoring Centre (WHO‐UMC) system. Univariate and multivariate logistic regressions were carried out to analyze the risk factors of ADRs. Our results showed that the prevalence of ADRs was 37.8% in the patients, which was predominated by drug‐induced gastrointestinal disorders and liver system disorders (23.0% vs. 13.8%). The ADR could be explained by the use of lopinavir/ ritonavir and umifenovir by 63.8% and 18.1%, respectively. There were 96.8% of ADRs that occurred within 14 days of hospitalization. Multivariable analysis showed that length of stay (odds ratio (OR): 2.02; 95% confidence interval (CI) 1.03–3.96; P = 0.04), number of drugs used in the hospital (OR: 3.17; 95% CI 1.60–6.27; P = 0.001) and underlying basic diseases (OR: 2.07; 95% CI 1.02–4.23; P = 0.04) were independent risk factor for ADRs in the patients. Together, the incidence of ADRs was significantly high during the treatment period. Moreover, the active monitoring of the CHPS system reflected ADRs during COVID‐19 treatment in the real world, which provided reference for safe medication in the clinic.

Systematic review with meta‐analysis: liver manifestations and outcomes in COVID‐19

“…Ninety‐two articles (of which four included pregnant patients) reported adult patients infected with SARS‐CoV‐2. Eleven articles included paediatric population, and four articles reported both adults and children infected with SARS‐CoV‐2 2,7,14‐118 . (Tables S1, S2 and S3) A total of 20 874 patients were included, of which 38 were pregnant patients, 395 were paediatric patients and the rest were adult patients.…”

“…Twelve articles were not from China. Three articles from the United States of America, 14,75,78 one each from United Kingdom (UK), 81 Italy, 100 Thailand, 57 France, 64 South Korea, 51 Singapore, 115 Hong Kong 76 and Iran 66 . One was a multicentre trial on remdesivir conducted simultaneously at USA, Japan, Italy, Austria, France, Germany, Netherlands, Spain and Canada 93 .…”

“…In total, 12 articles reported DILI 7,15,64,65,84,93,113‐118 . Two article sample size <10 and were excluded from the pooled analysis 64,114 .…”

“…While remdesivir frequently led to elevated aminotransferases 64,118 . In some studies DILI was attributed to more than one drug 65,115 . (Figure S14) A recent trial included 158 patients in remdesivir arm and 79 in the placebo arm 93 .…”

COVID‐19: A Defining Moment for Clinical Pharmacology?

“…This knowledge can be harnessed and translated immediately to optimize dosing and treatment regimens: Absorption, distribution, metabolism, and pharmacokinetics; Pharmacokinetics in special populations and the role of factors such as age (including pediatrics 5 and geriatrics), gender, ethnicity, morphometry, disease, and organ function; Drug–drug interactions (DDIs): infectious diseases are often best treated with more than one drug, and several potential combination therapies have already been proposed for COVID‐19 2 . In addition, age is associated with concomitant medications, which may cause DDIs with COVID‐19 drugs, especially those commonly used in older people; Pharmacogenomics and precision medicine; Relationship between pharmacokinetics and pharmacodynamics (biomarker) response; Relationship between exposure and adverse events 6,7 …”