What is the adverse effects profile of vonaprazan (Potassium-competitive acid blocker)?

Adverse Effects Profile of Vonaprazan

Overall Safety Profile

Vonaprazan is generally well-tolerated with short-term and medium-term safety profiles comparable to proton pump inhibitors (PPIs), with the most common adverse effects being mild to moderate gastrointestinal symptoms including constipation, diarrhea, abdominal pain, nausea, and dyspepsia. 1, 2, 3

Common Adverse Effects (Occurring in 8-17% of Patients)

Gastrointestinal Effects

• Constipation - one of the most frequently reported adverse effects 4, 3, 5
• Diarrhea or loose stools - notably, vonaprazan may actually cause less diarrhea compared to PPIs (statistically significant reduction) 5
• Abdominal pain 3, 6
• Nausea 4, 3
• Dyspepsia 3, 6
• Flatulence 6

Other Common Effects

• Nasopharyngitis 4, 6
• Headache 6

Metabolic and Laboratory Effects

Gastrin Elevation

• Vonaprazan elevates serum gastrin levels higher than PPIs due to more potent acid suppression 7, 2, 4
• Gastrin levels remain elevated during treatment but return toward baseline within weeks after discontinuation 7, 2
• This elevation is 2-3 times greater than that seen with lansoprazole 4

Chromogranin A (CgA) Interference

• Vonaprazan increases CgA levels, which may cause false-positive results in diagnostic investigations for neuroendocrine tumors 8
• CgA levels should be assessed at least 4 weeks after stopping vonaprazan treatment 8

Hepatic Effects

• No severe liver toxicity has been reported in pre-approval clinical studies 4
• Transaminase elevations have not been a significant concern with vonaprazan (unlike atopaxar, a different drug class) 4

Infectious Risk

• Vonaprazan may be associated with increased risk of enteric infections, including Clostridium difficile, similar to PPIs due to acid suppression 7, 2

Long-Term Safety Considerations

Neuroendocrine Concerns

• No neuroendocrine tumors have been reported in patients receiving vonaprazan in clinical studies 4
• However, long-term safety data remain more limited compared to the extensive experience with PPIs 1, 2

Comparative Safety to PPIs

• Meta-analysis of 18 randomized controlled trials (7,932 participants) showed no significant increase in overall adverse effects compared to PPIs (95% CI = 0.987-1.095, p = 0.141) 5
• No significant differences were found between vonaprazan and PPIs for: constipation, rash/eruption, nausea/vomiting, bloating, dysgeusia, neurological disorders, upper respiratory tract infection, or abnormal laboratory investigations 5

Drug Interactions and Special Populations

Hepatic Impairment

• Mean AUC increased by 2.6 times in patients with severe liver dysfunction compared to healthy subjects 4
• No significant changes in plasma protein binding occur 4

Renal Impairment

• Mean AUC increased by 2.4 times in patients with severe renal dysfunction compared to healthy subjects 4

Drug-Drug Interactions

• When co-administered with clarithromycin, vonaprazan AUC increased by 1.8 times due to mutual metabolic inhibition 4
• Vonaprazan is a weak CYP3A inhibitor and CYP2C19 inhibitor, requiring monitoring when used with certain substrates 8

Serious Adverse Effects (Rare)

• Neither severe liver toxicity nor neuroendocrine tumors have been reported in clinical studies 4
• The safety profile appears favorable with no black box warnings specific to vonaprazan 8

Clinical Monitoring Recommendations

For Constipation Management

• Discontinue nonessential constipating medications 2
• Encourage increased fluid intake and physical activity 2
• Consider added dietary fiber 2
• Use standard treatments (bisacodyl or polyethylene glycol) if constipation persists 2

For Laboratory Monitoring

• Stop vonaprazan at least 4 weeks before secretin stimulation testing to allow gastrin levels to normalize 8
• Repeat CgA testing if initial levels are high, using the same commercial laboratory 8

Key Clinical Pitfalls to Avoid

• Do not assume cross-reactivity with PPIs in patients with PPI allergies—vonaprazan has a distinct chemical structure and mechanism 7
• Do not overlook the higher gastrin elevation compared to PPIs, though clinical significance remains unclear 7, 4
• Consider other causes of gastrointestinal symptoms beyond vonaprazan, as these are common in patients with acid-related disorders 2