Direct-acting antiviral agent use and gastrointestinal safety in patients with chronic hepatitis C: a pharmacovigilance study based on FDAAdverse Event Reporting System.

Abstract

Gastrointestinal adverse drug reactions (GADRs) of direct-acting antiviral agents (DAAs) in patients with chronic hepatitis C are underestimated. This study aimed to comprehensively evaluate the gastrointestinal safety of DAAs in patients with chronic hepatitis C. The US FDA Adverse Event Reporting System database was searched for GADR cases reported from 01 to 2012 to 30 September 2021. Twelve DAA types used for hepatitis C virus were included. The top 30 GADRs were assessed based on the use of DAAs, number of cases, and clinical features. A case-non-case disproportionality approach was used to confirm pharmacovigilance signals, whereby reporting odds ratios (ROR) with 95% CI were calculated. Nausea (70.01/1000), diarrhoea (39.10/1000), and vomiting (31.68/1000) accounted for the highest number of cases. The pooled median time-to-onset of the top 30 GADRs was 13 days (Q1-Q3: 2-38) and the proportion of drug discontinuation was 19.17%. The highest number of DAA-related cases involved ledipasvir/sofosbuvir (21.86%), sofosbuvir/velpatasvir (21.77%), and sofosbuvir (13.41%). When DAAs were considered as a class drug, after adjusting for age, sex, concomitant diseases and drugs that potentially induced GADRs, significant RORs for specific GADRs were noted, including abdominal discomfort (1.62, 95% CI 1.32-1.99), constipation (1.54, 95% CI 1.26-1.89), dyspepsia (1.25, 95% CI 1.01-1.55), abdominal distension (1.36, 95% CI 1.05-1.75), faeces discoloured (1.77, 95% CI 1.15-2.73), and gastric ulcer (2.37, 95% CI 1.28-4.41). Clinicians should have a deeper understanding of GADRs to improve the gastrointestinal tolerance of patients with chronic hepatitis C.