What are the considerations for using voquezna (vonoprazan) in adult patients with a history of gastrointestinal disorders, such as Gastroesophageal Reflux Disease (GERD) or peptic ulcer disease, and Helicobacter pylori infection?

Voquezna (Vonoprazan) for Gastrointestinal Disorders

Vonoprazan is FDA-approved for healing erosive esophagitis (20 mg daily for up to 8 weeks), maintenance of healed erosive esophagitis (10 mg daily), relief of heartburn in non-erosive GERD (10 mg daily), and H. pylori eradication (20 mg twice daily with antibiotics for 14 days), but should not be used as first-line therapy for most patients due to higher cost and limited long-term safety data compared to standard PPIs. 1

When to Use Vonoprazan vs Standard PPIs

First-Line Therapy (Use Standard PPIs)

• Standard PPIs (omeprazole, lansoprazole, pantoprazole) remain first-line for most GERD and peptic ulcer disease due to extensive safety data, lower cost, and proven efficacy comparable to vonoprazan in mild-to-moderate disease 2, 3
• PPIs are efficacious for functional dyspepsia and should be used at the lowest dose that controls symptoms 2
• For uncomplicated GERD and nonerosive reflux disease, most patients should be considered for PPI de-prescribing after symptom resolution 2

Second-Line Therapy (Consider Vonoprazan)

Vonoprazan should be reserved for:

• Severe erosive esophagitis (LA grade C/D) where vonoprazan demonstrates superior healing rates of 75-77% versus 62% for lansoprazole, with significantly better maintenance (5-13% recurrence vs 39%) 3, 4
• PPI-refractory GERD after failure of twice-daily PPI therapy in patients with confirmed disease (LA grade B or greater, Barrett's esophagus, peptic stricture, or acid exposure time >6% on pH monitoring) 3, 5
• H. pylori eradication, particularly with clarithromycin-resistant strains (66-70% eradication vs 32% with PPIs) or after PPI-based regimen failure 3, 6, 7

H. pylori Eradication Regimens

Vonoprazan-Based Triple Therapy (Preferred)

• Vonoprazan 20 mg + amoxicillin 1000 mg + clarithromycin 500 mg, all twice daily for 14 days 1
• Achieves 92% eradication rate versus 80% with PPI-based triple therapy 3
• Particularly superior for clarithromycin-resistant strains 3, 7

Vonoprazan-Based Dual Therapy (Alternative)

• Vonoprazan 20 mg + amoxicillin 1000 mg, both twice daily for 14 days 1
• Appropriate when clarithromycin resistance is suspected or patient has penicillin allergy concerns requiring alternative antibiotics 6, 7

Key Advantages Over PPI-Based Regimens

• Not metabolized by CYP2C19, providing consistent efficacy regardless of genetic polymorphisms 3, 8
• More potent and prolonged acid suppression through potassium-competitive acid blockade 8, 5
• No food effect, can be taken with or without meals 1

Peptic Ulcer Disease Treatment

Gastric Ulcers

• Vonoprazan 20 mg once daily for 8 weeks achieves 94% healing rates (noninferior to lansoprazole 30 mg) 9
• H. pylori eradication is strongly recommended in all infected patients with gastric ulcer history 2

Duodenal Ulcers

• Vonoprazan 20 mg once daily for 6 weeks achieves 96-98% healing rates 9
• Shorter duration than gastric ulcers due to higher baseline healing rates 9

Dosing Adjustments

Renal Impairment

• eGFR ≥30 mL/min: Standard dosing (20 mg twice daily for H. pylori) 1
• eGFR <30 mL/min: Use not recommended for H. pylori treatment 1
• No adjustment needed for erosive esophagitis or GERD indications 1

Hepatic Impairment

• Child-Pugh Class A: Standard dosing 1
• Child-Pugh Class B: 10 mg once daily for erosive esophagitis; not recommended for H. pylori treatment 1
• Child-Pugh Class C: 10 mg once daily for erosive esophagitis; not recommended for H. pylori treatment 1

Safety Considerations and Monitoring

Contraindications

• Known hypersensitivity to vonoprazan (including anaphylactic shock) 1
• Concomitant use with rilpivirine-containing products 1

Warnings Requiring Clinical Vigilance

• Gastric malignancy: Consider endoscopy in older patients or those with suboptimal response, as symptomatic improvement does not exclude malignancy 1
• Acute tubulointerstitial nephritis: Discontinue if suspected 1
• Clostridioides difficile-associated diarrhea: Use shortest duration appropriate; consider CDAD in patients with persistent diarrhea 1
• Bone fracture risk: Increased with high-dose, long-term therapy; manage at-risk patients per osteoporosis guidelines 1
• Vitamin B12 deficiency: Monitor in patients on long-term therapy with clinical symptoms of deficiency 1
• Hypomagnesemia: Consider monitoring magnesium levels before initiation and periodically in patients on prolonged treatment or taking drugs with increased toxicity in hypomagnesemia (digoxin) or drugs causing hypomagnesemia (diuretics) 1

Common Adverse Effects

• Gastritis (3-6%), diarrhea (2-3%), abdominal pain (2-4%), nausea (2%), constipation (2%), dyspepsia (4%) 1
• Generally well tolerated with discontinuation rates of 2.3% in triple therapy and 0.9% in dual therapy 1

Conditions Requiring Long-Term PPI/Vonoprazan Therapy

Patients who should NOT be considered for de-prescribing:

• Barrett's esophagus 2
• Clinically significant erosive esophagitis (LA grade C/D) 2
• History of severe erosive esophagitis, esophageal ulcer, or peptic stricture 2
• Gastroprotection in high-risk NSAID/aspirin users at high risk for GI bleeding 2
• Secondary prevention of gastric and duodenal peptic ulcers without concomitant antiplatelet drugs 2

Critical Pitfalls to Avoid

• Do not use vonoprazan as first-line therapy when cost-effective PPIs would suffice 3
• Do not prescribe vonoprazan for mild GERD without first attempting standard PPI therapy 3
• Do not exceed maximum daily acetaminophen doses (4 g/24 hours) when using fixed-dose opioid combinations for pain in patients on vonoprazan 2
• Do not assume all dyspepsia requires long-term acid suppression—most patients with nonerosive disease should be considered for trial of de-prescribing 2
• Do not forget to confirm H. pylori eradication in patients at increased risk for gastric cancer after test-and-treat strategy 2
• Do not use vonoprazan in Child-Pugh Class B or C hepatic impairment for H. pylori treatment 1