What's the next step for a patient with persistent gastroesophageal reflux (GER) despite taking famotidine (H2 receptor antagonist) 40mg every night at bedtime (QHS)?

Switch to a Proton Pump Inhibitor

For a patient with persistent gastroesophageal reflux despite famotidine 40mg at bedtime, you should discontinue the H2-receptor antagonist and initiate a proton pump inhibitor (PPI) as first-line therapy, as PPIs are significantly more effective than H2RAs for GERD symptom control and healing. 1

Why PPIs Over Continued H2RA Therapy

• PPIs are superior to H2-receptor antagonists for both symptom relief and healing of erosive esophagitis in GERD patients, with H2RAs being only marginally better than placebo 1
• The American Gastroenterological Association explicitly recommends against adding a nocturnal H2RA to PPI therapy, as there is no evidence of improved efficacy with this combination approach 1
• Famotidine trials show that even at 20mg twice daily (higher total daily dose than your patient's current regimen), only 82% of symptomatic GERD patients improved by 6 weeks, compared to 62% with placebo 2

Initial PPI Dosing Strategy

• Start with a standard once-daily PPI dose taken 30 minutes before the first meal of the day for a 4-8 week therapeutic trial 1, 3
• Verify proper timing of administration, as taking PPIs 30 minutes before meals is critical for optimal acid suppression 3
• If symptoms persist after 4-8 weeks on once-daily dosing, escalate to twice-daily PPI therapy (before breakfast and dinner) rather than continuing ineffective H2RA therapy 1

When Standard PPI Therapy Fails

If symptoms persist despite twice-daily PPI therapy, the diagnostic approach changes:

• Perform upper endoscopy first to assess for erosive esophagitis (Los Angeles grade B or higher), Barrett's esophagus, or other structural causes 1, 3
• If endoscopy shows normal findings or only LA grade A esophagitis, proceed with 96-hour wireless pH monitoring off PPI therapy to confirm pathologic acid exposure and phenotype the reflux 1, 3
• Consider pH/impedance monitoring rather than pH monitoring alone in PPI non-responders, as this detects both acid and non-acid reflux episodes that may be driving persistent symptoms 1

Common Pitfalls to Avoid

• Do not empirically escalate H2RA doses or add PPIs to H2RAs without first switching to PPI monotherapy, as combination therapy lacks evidence 1
• Do not continue long-term acid suppression without objective confirmation of GERD through endoscopy or pH monitoring, especially if symptoms persist 1, 3
• Recognize that up to 60% of PPI-refractory patients may have functional heartburn or reflux hypersensitivity rather than true acid-mediated GERD, requiring neuromodulators or behavioral therapy instead of further acid suppression 1, 3
• Avoid assuming all persistent symptoms are due to inadequate acid control—persistent symptoms on twice-daily PPIs warrant diagnostic evaluation rather than further empiric dose escalation 3