Background and aims
Non-steroidal anti-inflammatory drugs (NSAIDs) have topical and systemic effects on prostaglandins involved in regulating gastrointestinal (GI) mucosal defence systems. This systematic review investigated whether ibuprofen administered at over-the-counter (OTC) doses (oral, ≤1200 mg/day, single/multiple doses or paediatric equivalent) is associated with increased GI adverse events (AEs) compared with paracetamol, placebo or other NSAIDs in adults and children. The results reported here focus on OTC ibuprofen doses administered for ≤10 days compared with paracetamol and placebo only. 
Methods
A literature search was performed following PRISMA guidelines in July 2018 using PubMed and Embase, focusing on published literature reporting GI safety and ibuprofen. No date limits were applied.
Results
2409 unique records were identified. 69 studies were included, predominantly randomised controlled trials (RCTs) (n=46) with several meta- or pooled analyses (n=4), observational/case-control studies (n=3) and retrospective analyses (n=16) across multiple treatment settings. Of these, 28 studies reported OTC doses of ibuprofen for ≤10 days versus placebo or OTC paracetamol. In adults, a meta-analysis established GI AE incidence rates were not statistically different (p=0.420) between ibuprofen and placebo. Additionally, in 16 RCTs, ibuprofen was associated with similar incidences of GI AEs compared with placebo or paracetamol. A multivariate analysis in one RCT also showed a lower GI risk for ibuprofen compared with paracetamol (p=0.01). In children, 5 RCTs demonstrated similar incidences of GI AEs for ibuprofen versus placebo or paracetamol. 
Conclusions
Published literature demonstrates that ibuprofen at OTC doses and duration has similar GI tolerability to placebo and OTC paracetamol.

A SYSTEMATIC REVIEW OF THE GASTROINTESTINAL SAFETY PROFILE OF IBUPROFEN AT OVER-THE-COUNTER DOSES