Can Acid Reflux Patients Take PPIs and H2RAs Concomitantly?

Historically, experts have expected histamine-2 receptor antagonists to inhibit proton pump inhibitor activation from a mechanistic perspective.

Historically, experts have expected histamine-2 receptor antagonists (H2RAs) to inhibit proton pump inhibitor (PPI) activation from a mechanistic perspective. Because of this expectation, health care providers usually recommend against concomitant therapy for acid reflux.

However, a 2007 study first provided evidence that concurrent intravenous dosing of a PPI and H2RA improved gastric pH control. More recently, researchers from the Medical University of South Carolina indicated that oral omeprazole and ranitidine potentiate one another’s effect on prolonged acid reflux control.

The study authors, whose work was published in Pharmacotherapy, enrolled PPI- and H2RA-naïve volunteers in their prospective, randomized, double-blind, 3-way crossover study.

They randomized patients to 3 treatment arms:

· Ranitidine 300 mg plus placebo

· Omeprazole 40 mg plus placebo

· Ranitidine 300 mg plus omeprazole 40 mg

The researchers administered medication daily at 8 AM (30 minutes before a standardized breakfast) for 1 week with washout periods between regimens. They measured gastric pH on day 7 of each regimen for 8 hours (9 AM to 5 PM) after a standard breakfast.

The study results showed that H2RAs did not adversely affect PPIs’ efficacy. In addition, this concurrent therapy produced superior acid reflux control than either agent alone.

H2RAs do not completely inactivate PPIs because of the direct action of acetylcholine and gastrin on the parietal cells, as well as the drugs’ relatively shorter half-life compared with PPIs.

Previous opinion blamed breakthrough symptoms in patients taking both types of acid suppressions on concomitant therapy. On the contrary, these findings support the use of both agents to control breakthrough symptoms.

H2RAs may increase PPI bioavailability by reducing stomach content acidity. A high pH protects the PPI from degradation and expedites the dissolution of its granules. PPIs also provide better control over mealtime acid release than H2RAs.

The researchers recommended further study in patients with gastroesophageal reflux disease and erosive esophagitis.

Once-daily concomitant PPI and H2RA could improve adherence and safety in Barrett’s esophagus patients on twice-daily PPI therapy. The addition of a PPI may also overcome H2RA tolerance in patients with upregulated gastrin and acetylcholine action on the parietal cells.