Utilization and safety of proton-pump inhibitors and histamine-2 receptor antagonists in children and adolescents: an observational cohort study

Abstract

Background: Little is known about the use of acid-suppressing treatments and related safety events in children.

Objective: This study compared patient characteristics and safety outcomes among children prescribed acid-suppressing drugs for the first time.

Methods: The Health Improvement Network was used to determine the characteristics of children prescribed a proton pump inhibitor (PPI; esomeprazole or another PPI) or a histamine-2 receptor antagonist (H₂RA) by UK primary care physicians between October 2009 and September 2012. Pre-defined safety outcomes were compared among the treatment groups in up to 18 months of follow-up.

Results: The cohorts comprised 8,172 patients on PPIs (including 24 patients on esomeprazole) and 7,905 on H₂RAs. The baseline characteristics were similar between cohorts, although the children in the PPI cohorts tended to be older. No safety outcomes occurred in the esomeprazole cohort. In the other-PPIs cohort, 92 safety outcomes occurred, most commonly gastroenteritis (n = 36; 39.1%). In the H₂RAs cohort, 193 safety outcomes occurred, most commonly gastroenteritis (n = 62; 32.1%). The incidence of most safety outcomes was higher in the H₂RAs cohort than in the other-PPIs cohort, including failure to thrive (3.11 [95% confidence interval (CI) = 2.25–4.28] vs 0.49 per 1,000 person-years [95% CI = 0.22–1.07]) and gastroenteritis (5.27 [95% CI = 4.11–6.75] vs 3.04 per 1,000 person-years [95% CI = 2.20–4.20]).

Conclusion: Esomeprazole is rarely prescribed to children when they first require acid-suppressing medication, compared with other PPIs/H₂RAs. Overall, more safety outcomes occurred in the H₂RAs cohort than in the PPI cohorts.

Keywords:

• Acid-suppressing drugs
• gastroesophageal reflux disease
• children
• drug safety
• pharmacoepidemiology
• The Health Improvement Network (THIN)

Transparency

Declaration of funding

This study was funded in part by AstraZeneca Gothenburg, Mölndal, Sweden.

Declaration of financial/other relationships

AR and LAGR work for CEIFE, which has received research funding from AstraZeneca R&D, Mölndal, Sweden, and Bayer Pharma AG, Berlin, Germany. LAGR has also received honoraria for serving on scientific advisory boards for Bayer. SJ is an employee of AstraZeneca R&D, Mölndal, Sweden, and owns stock or options. PN was an employee of AstraZeneca at the time the study was conducted and the manuscript initiated. CMRO peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgments

Writing support was provided by Dr Nesta Hughes of Oxford PharmaGenesis, Oxford, UK, and was funded by AstraZeneca Gothenburg, Sweden. We gratefully acknowledge the expert input from Professor Francisco J de Abajo (University of Alcalá, Madrid, Spain) and Professor Ernst Kuipers (Erasmus University Medical Centre, Rotterdam, Netherlands) in validating the safety outcomes cases.