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

Abstract

Summary 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.

Does Gastroesophageal Reflux Cause Apnea in Preterm Infants?

“…The proton pump inhibitor, omeprazole, reduces symptoms, endoscopic and histologic signs of esophagitis, and intragastric acidity in infants with cimetidine-resistant peptic esophagitis [50] . Similar results have been found in infants using another proton pump inhibitor, famotidine [51] . Future trials of these agents should include evaluations for a benefi cial effect on apnea of prematurity in a subgroup of infants.…”

Oral sodium citrate increases nausea amongst elective Cesarean delivery patients

“…16 Histamine-2 blockers, including famotidine, are frequently used in infants to treat gastroesophageal reflux or prevent stress ulceration. 17,18 In conclusion, nausea during Cesarean delivery is more frequent in women receiving oral sodium citrate rather than iv famotidine. Therefore, we recommend the preoperative use of a histamine-2 blocker rather than oral sodium citrate to neutralize maternal gastric acidity in parturients scheduled for elective Cesarean delivery under spinal anesthesia.…”

Differential diagnosis of apneas in preterm infants

“…Ad (d): In GER treatment in preterm infants, the positioning of the infant on the abdomen or on the left side simultaneously with cardiorespiratory monitoring [9], feeding with thickened milk or formula [41], frequent feeding with small doses [27], and antagonists of histamine-2 receptors [28] are recommended. With the exception of pharmacological treatment, all recommendations mentioned above were applied in our study.…”