Famotidine for infant gastro-oesophageal reflux: a multi-centre, randomized, placebo-controlled, withdrawal trial

Aliment Pharmacol Ther. 2003 May 1;17(9):1097-107. doi: 10.1046/j.1365-2036.2003.01559.x.


Background: Gastro-oesophageal reflux afflicts up to 7% of all infants. Histamine-2 receptor antagonists are the most commonly prescribed medications for this disorder, but few controlled studies support this practice.

Aim: To evaluate the safety and efficacy of famotidine for infant gastro-oesophageal reflux disease.

Methods: Thirty-five infants, 1.3-10.5 months of age, entered an 8-week, multi-centre, randomized, placebo-controlled, two-phase trial: first 4 weeks, observer-blind comparison of famotidine 0.5 mg/kg and famotidine 1.0 mg/kg; second 4 weeks, double-blind withdrawal comparison (safety and efficacy) of each dose with placebo.

Results: No serious adverse events were reported. Eleven patients had 16 non-serious, possibly drug-related adverse experiences: 6 patients with agitation or irritability (manifested as head-rubbing in two), 3 patients with somnolence, 2 patients with anorexia, 2 with headache, 1 patient with vomiting, 1 patient with hiccups, and 1 patient with candidiasis. Of the 35 infants, 27 completed Part I. There were significant score improvements for famotidine 0.5 mg/kg in regurgitation frequency (P = 0.04), and for famotidine 1.0 mg/kg in crying time (P = 0.027) and regurgitation frequency (P = 0.004) and volume (P = 0.01). Eight infants completed Part II on double-blind treatment, which was insufficient for meaningful comparisons.

Conclusions: Histamine-2 receptor antagonists may cause agitation and headache in infants. A possibly efficacious famotidine dose for infants is 0.5 mg/kg (frequency adjusted for age). As 1.0 mg/kg may be more efficacious in some, the dosage may require individualization based on response. Further sizeable placebo-controlled evaluations of histamine-2 receptor antagonists in infants with gastro-oesophageal reflux disease are warranted.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Famotidine / administration & dosage*
  • Famotidine / adverse effects
  • Female
  • Gastroesophageal Reflux / drug therapy*
  • Histamine H2 Antagonists / administration & dosage*
  • Histamine H2 Antagonists / adverse effects
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Treatment Outcome


  • Histamine H2 Antagonists
  • Famotidine