Adverse effects reported in the use of gastroesophageal reflux disease treatments in children: a 10 years literature review

Abstract

Gastroesophageal reflux (GER) is commonly observed in children, particularly during the first year of life. Pharmacological therapy is mostly reserved for symptomatic infants diagnosed with GER disease (GERD), usually as defined in a recent consensus statement. The purpose of the present article was to review the reported adverse effects of pharmacological agents used in the treatment of paediatric GERD. We conducted this review using the electronic journal database Pubmed and Cochrane database systematic reviews using the latest 10-year period (1 January 2003 to 31 December 2012). Our search strategy included the following keywords: omeprazole, esomeprazole, lansoprazole, pantoprazole, rabeprazole, rantidine, cimetidine, famotidine, nizatidine, domperidone, metoclopramide, betanechol, erythromycin, baclofen, alginate. We used Pubmed's own filter of: 'child: birth-18 years'. All full articles were reviewed and we only included randomized controlled trials retrieved from our search. We addressed a summary of our search on a drug-by-drug basis with regard to its mechanism of action and clinical applications, and reviewed all of the adverse effects reported and the safety profile of each drug. Adverse effects have been reported in at least 23% of patients treated with histamine H 2 receptor antagonists (H 2 RAs) and 34% of those treated with proton pump inhibitors (PPIs), and mostly include headaches, diarrhoea, nausea (H 2 RAs and PPIs) and constipation (PPIs). Acid suppression may place immune-deficient infants and children, or those with indwelling catheters, at risk for the development of lower respiratory tract infections and nosocomial sepsis. Prokinetic agents have many adverse effects, without major benefits to support their routine use.

Review shows that parental reassurance and nutritional advice help to optimise the management of functional gastrointestinal disorders in infants

“…One review of children up to 18 years of age reported that at least 23% of patients treated with histamine receptor 2 antagonists experienced side effects, as did 34% of those treated with proton pump inhibitors 32. Concerns have been raised with regard to the impact of proton pump inhibitors on the gut microbiome and the association between using proton pump inhibitors and small bowel bacterial overgrowth in children 33, 34.…”

Toxicity of long-term use of proton pump inhibitors in children

“…A recent review by Cohen et al 12 reported adverse effects in 34% of children treated with PPIs, including most commonly headaches, nausea, diarrhoea and constipation. Additionally, prolonged use of PPIs has raised concerns about hypochlorhydria and hypergastrinaemia, increased risk of infections, vitamin and mineral deficiencies, adverse bone health, food allergy and drug interactions.…”

“…There is increasing evidence that gastric acid suppression may place susceptible infants and children, particularly those with indwelling catheters or defective immune systems, at risk for nosocomial infections 12. Safety studies on the use of histamine-2 receptor antagonists (H2RAs) particularly in neonatal intensive care with hospital-acquired pathogens raised the following concerns: these gastric acid inhibitors in neonatal intensive care have been identified as a risk factor for necrotising enterocolitis,13 sepsis and meningitis,14 and bloodstream infections with Candida species 15 16.…”

Eosinophilic Esophagitis: Treatment With Different Doses of Omeprazole in Children Under 16 Years

“…To date, adverse effects have not been reported after 6 months of treatment with PPIs in patients with EoE; however, adverse effects have been reported in patients with a 10-year history of gastroesophageal reflux disease (GERD) [9] and are more frequent in GERD (34%) than in EoE (8.3%). Other adverse effects include visual alterations, especially blurred vision.…”