Pharmacotherapy for GERD (Gastroesophageal Reflux Disease) (February 2004)

Treatment options for infants with gastroesophageal reflux disease (GERD) fall into three categories:

1) Lifestyle changes, which include diet/formula modifications and altered sleep position.
2) Pharmacotherapy to buffer gastric acid, reduce gastric acid secretion or alter GI motility.
3) Surgical therapy that includes operative techniques to reduce or eliminate GER.

Lifestyle Changes: For all infants and children with GER, conservative therapy, or lifestyle changes, are recommended, irrespective of disease severity. A complete history can reveal provocative lifestyle aspects, such as huge feedings at infrequent intervals in infants. When regurgitation has resulted in poor weight gain, thickened feedings may be beneficial. To thicken infant formula, add rice cereal (up to 1 tbsp./oz). Frequent, smaller feedings are encouraged. Evidence also supports a 1- or 2-week trial of a hypoallergenic formula in formula-fed infants with vomiting. Positioning therapy is a traditional part of anti-reflux management. In infants with GERD, the risk of SIDS outweighs the potential benefits of prone sleeping. Therefore, non-prone positioning during sleep is recommended. Prone positioning is acceptable while the infant is awake, particularly in the postprandial period. For older children, recommendations include: avoiding large meals; not lying down immediately after eating; losing weight if obese (a recent study confirmed that obesity is a strong risk factor for reflux disease ); avoiding exposure to tobacco smoke, caffeine, chocolate and spicy foods that provoke symptoms.

Pharmacotherapy: For patients with significant GERD who do not respond to lifestyle changes, antireflux pharmacotherapy is considered first-line treatment. The goals of such treatment are to control symptoms, promote healing of esophagitis if present, and prevent complications by reducing exposure of the esophagus or respiratory tract to acid refluxate. In addition, pharmacotherapy aims to improve the patient’s health-related quality of life and avoid adverse events of treatment. The following medical therapies are available for the treatment of GERD.


  • Acid-suppressive agents: i.e. histamine H2-receptor antagonists (H2RAs) and proton pump inhibitors (PPIs) that inhibit acid production in the parietal cell.
  • Acid neutralizers (antacids) which work locally to raise the pH of the refluxate.
  • Mucosal-protective agents, which bind with damaged mucosa to form a barrier against harmful acid reflux.
  • Prokinetic agents, which target the underlying motility dysfunction causing GERD.

Of these therapies, acid-suppressive agents have become the drugs of choice for GERD. Both PPIs and H2RAs effectively and safely treat the disease by reducing the amount of acid refluxate to which the esophagus or respiratory tract is exposed, thereby preventing symptoms and promoting healing. The PPIs covalently bond and deactivate the H+, K+-ATPase pumps. To be activated, PPIs require acid in the parietal cell canaliculus and are most effective when the parietal cell is stimulated by a meal following a fast. Optimal efficacy is achieved when the PPI is administered 30 minutes before meals. Specific acid-suppressive agents include:

H2RAs
Ranitidine (Zantac - 15 mg/ml), dosage 5 to 10 mg/kg/day divided TID
Adverse effects: headache, elevated transaminase, decrease dose with renal insufficiency.

Famotidine (Pepcid - 8 mg/ml), dosage 1 mg/kg/day divided BID
Adverse effects: headache, decrease dose with renal insufficiency

PPIs
Omeprazole (Prilosec), dosage 1 - 3.3 mg/kg/day QD or divided BID
Adverse effects: headache, diarrhea, abdominal pain, elevated tranaminase, and neutropenia (rare).

Lansoprazole (Prevacid), dosage 1.4 mg/kg/day
Adverse effects: headache, diarrhea, abdominal pain, elevated tranaminase, and neutropenia (rare).

Antacids neutralize gastric acid and are commonly used for short-term relief of intermittent GER symptoms in children and adolescents. Although there appears to be little risk to this approach, it has not been formally studied. In infants, treatment with aluminum-containing antacids significantly increases plasma aluminum levels . Because more convenient and safe alternatives are available, chronic antacid therapy is generally not recommended.

Mucosal-protective agents, such as sucralfate, adhere to lesions and protect the esophageal mucosal surface. Because sucralfate is an aluminum complex, potential adverse effects of aluminum in infants and children need to be considered. Available data are inadequate for determining sucralfate safety or efficacy in children.

Prokinetic agents: The withdrawal of Cisapride from the U.S. market has lessened the role of promotility agents for treating GERD. There is insufficient evidence that prokinetic agents such as Metoclopramide (Reglan) and Bethanecol (Urecholine) are effective in the treatment of GERD in infants and children. Additionally, each of these agents has significant risks, including anti-dopaminergic side effects (up to 30% of patients), drowsiness, anxiety, agitation and motor restlessness, and dystonic reactions in 1% of patients. Parkinsonian symptoms such as tremor, rigidity, akinesia, tardive dyskinesia are rare except with high doses—but may be irreversible.

Diagnostic studies and/or consultation with a pediatric gastroenterologist are recommended for patients with suspected GERD who are not responding to conservative therapy/lifestyle changes, have poor weight gain and/or are having pulmonary symptoms.