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


OBJECTIVE
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.
Orenstein
S R
SR
Pediatric Gastroenterology, University of Pittsburgh School of Medicine, Children's Hospital of Pittsburgh, Pittsburgh, PA 15213-2583, USA. orenst@chplink.chp.edu
Shalaby
T M
TM
Devandry
S N
SN
Liacouras
C A
CA
Czinn
S J
SJ
Dice
J E
JE
Simon
T J
TJ
Ahrens
S P
SP
Stauffer
L A
LA
D000284:Administration, Oral; D015738:Famotidine / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D005764:Gastroesophageal Reflux / Q000188:drug therapy*; D006635:Histamine H2 Antagonists / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D016896:Treatment Outcome
D006635:Histamine H2 Antagonists; D015738:Famotidine