Is it clinically appropriate to combine voquezna with a Proton Pump Inhibitor (PPI)?

Combining Vonoprazan (Voquezna) with a PPI is Not Clinically Appropriate

It does not make clinical sense to combine vonoprazan (Voquezna) with a proton pump inhibitor (PPI) as they have overlapping mechanisms of acid suppression and there is no evidence supporting improved outcomes with this combination. 1, 2

Rationale Against Combination Therapy

Overlapping Mechanisms and Pharmacology

• Vonoprazan is a potassium-competitive acid blocker (P-CAB) that works by competing with potassium on the proton pump to inhibit gastric acid secretion, providing potent acid suppression on its own 3
• PPIs also inhibit gastric acid secretion through a different but overlapping mechanism, and combining these agents has not been studied or recommended in any clinical guidelines 1
• Vonoprazan provides more rapid onset of action, more potent acid suppression, and more consistent effects than PPIs, making additional acid suppression unnecessary 4, 5

Lack of Evidence for Combined Use

• Current clinical practice guidelines from the American Gastroenterological Association (AGA) do not recommend combining P-CABs with PPIs for any indication 1
• The FDA-approved labeling for Voquezna does not mention or support concomitant use with PPIs 2
• Clinical trials evaluating vonoprazan have compared it to PPIs as alternatives, not as combination therapy 4, 5

Potential Risks of Combination

• Combining two acid-suppressing medications could potentially increase the risk of adverse effects associated with profound acid suppression, including:
  • Increased risk of enteric infections and Clostridioides difficile-associated diarrhea 1, 2
  • Greater risk of vitamin B12 deficiency due to more profound hypochlorhydria 2
  • Increased risk of hypomagnesemia and mineral metabolism disturbances 2
  • Higher likelihood of fundic gland polyps with more profound acid suppression 2

Appropriate Clinical Applications of Vonoprazan

Indications Where Vonoprazan Should Be Used Instead of (Not With) PPIs

• Helicobacter pylori eradication: AGA guidelines recommend using P-CABs in place of PPIs in eradication regimens for most patients with H. pylori infection 1
  • Vonoprazan-based regimens demonstrate significantly higher eradication rates (92% vs 80%) compared to PPI-based regimens, particularly for clarithromycin-resistant strains 1, 5
• Severe erosive esophagitis (LA grade C/D): Vonoprazan may be considered as a therapeutic option for healing and maintenance of healing in patients with more severe erosive esophagitis 1

When to Consider Switching from PPI to Vonoprazan

• In patients with PPI treatment failures (e.g., refractory esophagitis) when confirmatory GERD evidence is present 1
• In patients with clarithromycin-resistant H. pylori infections, where vonoprazan-based regimens show superior eradication rates (66%-70% vs 32%) 1

Historical Context: PPI Combinations with Other Acid-Suppressing Agents

• While there is some evidence that combining a PPI with a histamine-2 receptor antagonist (H2RA) may enhance gastric acid suppression 6, this approach has not been widely adopted in clinical practice
• The AGA has focused on de-prescribing PPIs rather than combining acid-suppressing medications, emphasizing that patients should not use any medication when there is not a reasonable expectation of benefit 1

Conclusion

Combining vonoprazan with a PPI is not clinically appropriate or evidence-based. Instead, clinicians should use either vonoprazan or a PPI based on the specific clinical indication, patient characteristics, and prior treatment response. For conditions requiring more potent acid suppression, vonoprazan should be considered as an alternative to, not an addition to, PPI therapy.