What are the side effects of H2 (histamine-2) blockers in infants?

Side Effects of H2 Blockers in Infants

H2 receptor antagonists in infants can cause tachyphylaxis within 6 weeks of use and may increase the risk of community-acquired pneumonia, gastroenteritis, candidemia, and necrotizing enterocolitis in preterm infants. 1

Common Side Effects

H2 blockers (histamine-2 receptor antagonists) are used in pediatric populations for conditions such as gastroesophageal reflux disease (GERD) and gastric hypersecretion. However, they come with several potential side effects:

Gastrointestinal Effects

• Constipation
• Diarrhea
• Nausea and vomiting
• Abdominal discomfort/pain 2

Central Nervous System Effects

• Headache (sometimes severe)
• Malaise
• Dizziness
• Somnolence
• Sleep disturbances with bizarre dreams
• Rarely: mental confusion, agitation, depression, and hallucinations 2, 3

Specific Concerns in Infants

1. Tachyphylaxis:

   • Rapid development of tolerance within 6 weeks of initiation, limiting long-term effectiveness 1

2. Infection Risk:

   • Increased risk of community-acquired pneumonia
   • Higher susceptibility to gastroenteritis
   • Increased risk of candidemia
   • In preterm infants, significantly higher risk of necrotizing enterocolitis (NEC) 1, 4

3. Medication-Specific Concerns:

   • Cimetidine: Increased risk of liver disease and gynecomastia (may be generalizable to other H2RAs) 1
   • Ranitidine: Associated with sleep disturbances and bizarre dreams 3

Differences Between H2 Blockers

Different H2 blockers have varying potency, duration of action, and side effect profiles:

• Ranitidine: FDA-indicated for infants as young as 1 month; available as peppermint-flavored syrup; longer duration of action than cimetidine 1, 5
• Famotidine: FDA-indicated for children 1-16 years; available as cherry-banana-mint flavored suspension 1
• Cimetidine: Not FDA-indicated for children under 16 years; has more endocrinologic side effects that essentially preclude long-term use in children 1, 6
• Nizatidine: FDA-indicated for children 12 years and older; available as bubble gum-flavored solution 1

Risk-Benefit Considerations

The American Academy of Pediatrics guidelines caution that while H2RAs are effective at reducing acid secretion, their use should be carefully considered:

1. H2RAs are less effective than PPIs for symptom relief and healing of erosive esophagitis 1

2. Recent evidence suggests that both H2RAs and PPIs show:

   • No clinical benefit for reducing GERD symptoms like irritability
   • No improvement in feed tolerance or weight gain
   • Potential for increased risk of allergies and anaphylactic reactions 7

3. In preterm infants, a case-control study found that ranitidine use was associated with a 1.55 times higher odds of developing NEC 4

Monitoring and Precautions

When H2 blockers are prescribed for infants:

• Monitor for signs of infections, particularly respiratory and gastrointestinal
• Watch for changes in sleep patterns or unusual irritability
• Be aware of the potential for tachyphylaxis if symptoms return after initial improvement
• Consider the shortest effective duration of therapy to minimize risks
• In preterm infants, carefully weigh the risk-benefit ratio before initiating therapy 4

Alternative Approaches

Before considering H2 blockers for infants with suspected GERD, guidelines recommend trying non-pharmacological approaches first:

• Modifying maternal diet in breastfed infants
• Changing formula in formula-fed infants
• Reducing feeding volume while increasing frequency
• Thickening formula (except in preterm infants due to NEC risk)
• Positioning changes (upright or supervised prone position when awake) 1