What are the medications for Gastroesophageal Reflux Disease (GERD)?

Medications for Gastroesophageal Reflux Disease (GERD)

Proton pump inhibitors (PPIs) are the most effective medication class for treating GERD and should be considered first-line therapy for patients with documented GERD. 1

First-Line Medications

• Proton Pump Inhibitors (PPIs): Most effective medication class for GERD treatment, superior to histamine-2 receptor antagonists (H2RAs) and other agents 1, 2
  • Examples: omeprazole, lansoprazole, pantoprazole, rabeprazole, esomeprazole, dexlansoprazole 3, 4, 5
  • Dosing: Standard dose once daily, taken 30-60 minutes before breakfast 1
  • Indication: Treatment of heartburn and other symptoms associated with GERD for up to 4-8 weeks 4, 5
  • Mechanism: Irreversible binding to proton pumps, blocking H+/K+ exchange 3

Second-Line Medications

• Histamine-2 Receptor Antagonists (H2RAs): Less effective than PPIs but still superior to placebo 1, 6

  • Examples: ranitidine, cimetidine, famotidine, nizatidine 3
  • Dosing: Typically twice or three times daily 3
  • Indication: Relief of heartburn and other GERD symptoms 6
  • Limitation: Tachyphylaxis (diminishing effect) may develop with continued use 3

• Antacids: For on-demand relief of mild or breakthrough symptoms 3, 1

  • Examples: Aluminum/magnesium hydroxide formulations, calcium carbonate
  • Dosing: As needed for symptom relief
  • Best used: For intermittent, mild symptoms or breakthrough symptoms while on other therapies 1

Treatment Algorithm

Step 1: Initial Therapy

• Start with standard-dose PPI once daily for 4-8 weeks 1
• Examples: omeprazole 20 mg, lansoprazole 30 mg, pantoprazole 40 mg 4, 5
• Take 30-60 minutes before breakfast for optimal effect 1

Step 2: Inadequate Response

• If symptoms persist after 4-8 weeks, options include:
  • Increase to twice-daily PPI dosing 1
  • Consider adding H2RA at bedtime for nocturnal symptoms 1
  • Add alginate-containing antacids for breakthrough symptoms 1

Step 3: Persistent Symptoms

• If symptoms persist despite 8 weeks of twice-daily PPI therapy, endoscopic evaluation is recommended 1
• Consider pH monitoring to confirm GERD diagnosis in treatment-resistant cases 1

Special Considerations

• Erosive Esophagitis: PPIs are significantly more effective than H2RAs for healing erosive esophagitis 7, 8

  • Healing rates with PPIs exceed 90% compared to 50-60% with H2RAs 8
  • Maintenance therapy with PPIs is effective for up to 5 years 7

• Non-Erosive Reflux Disease (NERD):

  • Standard-dose PPI for 4-8 weeks followed by either step-down strategy or on-demand treatment 7
  • Response rates of 50-65% with PPIs (lower than for erosive disease but still highest among available treatments) 8

• Potassium-Competitive Acid Blockers (P-CABs):

  • Newer class of acid suppressants (e.g., vonoprazan, tegoprazan) 3
  • Should generally not be used as first-line therapy for patients with uninvestigated heartburn or NERD 3
  • May be considered in selected patients with documented acid-related reflux who fail therapy with twice-daily PPIs 3

Adjunctive Measures

• Lifestyle Modifications: Important as first-line therapy in both GER and GERD 3
  • Elevate head of bed for nighttime symptoms 1
  • Avoid meals within 3 hours of bedtime 1
  • Weight loss if overweight/obese 1
  • Avoid specific trigger foods 1

Common Pitfalls to Avoid

• Overuse of PPIs: Increasing evidence of inappropriate prescriptions for PPIs in patients without documented GERD 3
• Inadequate Dosing: PPIs should be taken 30-60 minutes before meals for optimal effect 3
• Using Prokinetics as Monotherapy: Agents like metoclopramide are ineffective as monotherapy and have significant side effects 1
• Continuing Indefinite PPI Therapy: Attempt to find the lowest effective dose for maintenance therapy 1
• Failing to Consider Differential Diagnosis: Not all heartburn symptoms are due to GERD; consider other diagnoses if treatment fails 1