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

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Abstract

Background

Gastrointestinal adverse drug reactions (GADRs) of direct-acting antiviral agents (DAAs) in patients with chronic hepatitis C are underestimated.

Aim

This study aimed to comprehensively evaluate the gastrointestinal safety of DAAs in patients with chronic hepatitis C.

Method

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.

Results

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).

Conclusion

Clinicians should have a deeper understanding of GADRs to improve the gastrointestinal tolerance of patients with chronic hepatitis C.

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Acknowledgements

The authors acknowledge the FDA Adverse Events Reporting System.

Funding

This study was funded by the National Natural Science Foundation of China (No. 82100872), the High-level Personnel Research Start-up Funding of Fujian medical university (No. XRCZX2020003), the Scientific Research Project of Fujian Education Department (No. JAT190175).

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Authors and Affiliations

  1. Department of Clinical Pharmacy and Pharmacy Administration, School of Pharmacy, Fujian Medical University, Fuzhou, China

    Wenhuo Xie, Xinyan Zhu, Linyao Wang, Jianbin Li & Yu Zhou

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  1. Wenhuo Xie
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  2. Xinyan Zhu
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Correspondence to Yu Zhou.

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Xie, W., Zhu, X., Wang, L. et al. Direct-acting antiviral agent use and gastrointestinal safety in patients with chronic hepatitis C: a pharmacovigilance study based on FDA Adverse Event Reporting System. Int J Clin Pharm 45, 154–162 (2023). https://doi.org/10.1007/s11096-022-01510-8

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  • DOI: https://doi.org/10.1007/s11096-022-01510-8

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