Is it safe to give ranitidine (histamine-2 (H2) receptor antagonist) to a pediatric patient with suspected gastroesophageal reflux disease (GERD) or peptic ulcer disease (PUD)?

Ranitidine Should NOT Be Given to Pediatric Patients

Ranitidine has been withdrawn from the market worldwide and is no longer available for use in pediatric or adult patients due to carcinogenicity concerns. In April 2020, both the FDA and European Medicines Agency requested all manufacturers to remove ranitidine products from the market due to the risk of N-nitrosodimethylamine (NDMA) contamination, a probable human carcinogen 1.

Current Status and Availability

• Ranitidine is not available for prescription or over-the-counter use - all formulations were removed from the US market in 2020 1
• The FDA drug label information provided is historical only and does not reflect current availability 2
• No ranitidine products should be in circulation, and any remaining stock should not be used 1

Alternative H2-Receptor Antagonist Options

If an H2-receptor antagonist is clinically indicated for pediatric GERD, famotidine is the preferred alternative:

• Famotidine is FDA-approved for children aged 1-16 years at a dose of 1 mg/kg/day divided in 2 doses 3
• Available as a cherry-banana-mint flavored oral suspension for ease of administration 3
• Generally considered safe with little clinical concern regarding safety in children 3

Important Limitations of H2-Receptor Antagonists

• Tachyphylaxis develops within 6 weeks of treatment initiation, limiting long-term effectiveness 4, 3
• H2-receptor antagonists are less effective than proton pump inhibitors for symptom relief and healing of erosive esophagitis 3
• May increase risk of community-acquired pneumonia, gastroenteritis, and candidemia 4, 3

Recommended Treatment Algorithm for Pediatric GERD

Step 1: Initial Management with Lifestyle Modifications

• Start with non-pharmacologic interventions first 4, 3:
  • Smaller, more frequent feedings to reduce gastric distension 4
  • Thickening formula (if formula-fed), though use caution in preterm infants due to necrotizing enterocolitis risk 4
  • Maternal elimination diet excluding milk and egg for 2-4 weeks if breastfeeding 4
  • Trial of extensively hydrolyzed or amino acid-based formula if formula-fed 4
  • Upright positioning when awake and supervised 4

Step 2: Pharmacologic Treatment (Only if Lifestyle Modifications Fail)

For mild, intermittent symptoms:

• Consider famotidine 1 mg/kg/day divided in 2 doses 3
• Reassess after 2-4 weeks 4

For moderate to severe symptoms or erosive esophagitis:

• Proton pump inhibitors are superior to H2-receptor antagonists 3
• Omeprazole 0.7-1 mg/kg/day is the preferred initial PPI dose for children aged 2-16 years 3
• Administer approximately 30 minutes before meals for optimal effect 3

For refractory cases:

• Switch from famotidine to omeprazole if no response after 2-4 weeks 3
• Increase omeprazole dose up to 3.3 mg/kg/day if partial response 3

Step 3: Duration and Monitoring

• Limit acid suppression therapy to 4-8 weeks maximum without further evaluation 4
• Re-evaluate response and discontinue if no clear benefit 4
• Do NOT use acid suppressive therapy solely for chronic cough without clear GER symptoms 4

Critical Precautions

• Treatment for GERD should NOT be used when there are no clinical features of GERD such as recurrent regurgitation, dystonic neck posturing in infants, or heartburn/epigastric pain in older children 4
• Acid suppression may increase risk of lower respiratory tract infections, particularly in infants 3
• Long-term PPI use (>2.5 years) is associated with enterochromaffin cell hyperplasia in up to 50% of children 3
• Consider referral to pediatric gastroenterology for refractory cases or diagnostic uncertainty 3