For an adult with gastro‑oesophageal reflux disease, should I prescribe dexlansoprazole (Dexilant) or pantoprazole (Protonix)?

Dexlansoprazole vs Pantoprazole for GERD

For an adult with gastroesophageal reflux disease, prescribe pantoprazole 40 mg once daily as first-line therapy rather than dexlansoprazole, because all PPIs demonstrate equivalent efficacy for symptom control and mucosal healing, and pantoprazole offers superior cost-effectiveness, wider formulary availability, and fewer prior-authorization barriers. 1, 2

Evidence-Based Rationale

Equivalent Clinical Efficacy

• All commercially available PPIs function as a class effect with similar efficacy for acid-related disorders, including healing of erosive esophagitis and symptom relief in GERD. 1, 2
• The 2022 AGA Clinical Practice Update explicitly states that any commercially available PPI can be used for initial GERD therapy, with selection guided by payor coverage, out-of-pocket costs, and prior experiences. 3
• Both pantoprazole and dexlansoprazole are FDA-approved for healing erosive esophagitis (up to 8 weeks), maintenance of healed erosive esophagitis, and treatment of symptomatic GERD. 4, 5

Cost and Accessibility Considerations

• Generic pantoprazole is the most cost-effective option for standard acid-related indications, whereas dexlansoprazole is substantially more expensive and is not considered cost-effective as first-line therapy. 1
• Pantoprazole is widely available in multiple formulations (oral capsule, oral suspension, and intravenous), while dexlansoprazole often requires prior-authorization from insurers, limiting immediate accessibility. 1
• Vonoprazan (a potassium-competitive acid blocker) costs approximately 10–20 times more than generic PPIs and should be reserved for documented PPI failures. 1

Practical Prescribing Algorithm

Step 1: Initial 4–8 Week Trial

• Prescribe pantoprazole 40 mg once daily, taken 30–60 minutes before breakfast. 2, 6
• Counsel the patient that initial symptom relief typically occurs within 5–7 days, with maximal therapeutic effect achieved after 4 weeks. 2
• Do not assess treatment failure before completing at least 4 weeks of properly timed PPI therapy. 2

Step 2: Inadequate Response After 4–8 Weeks

• Escalate to pantoprazole 40 mg twice daily (before breakfast and dinner) rather than switching to dexlansoprazole or another PPI. 3, 2
• Twice-daily PPI dosing shows a non-significant trend toward increased efficacy compared to once-daily dosing. 1

Step 3: Persistent Symptoms After 8 Weeks of Twice-Daily Therapy

• Perform upper endoscopy to evaluate for erosive esophagitis (Los Angeles grade B or higher), Barrett's esophagus, or alternative diagnoses. 3, 6
• If endoscopy is normal, conduct a 96-hour wireless pH study off PPI to differentiate true GERD from functional heartburn. 3, 6

Step 4: Long-Term Management

• After symptom control, taper to the lowest effective dose (e.g., pantoprazole 20 mg daily or on-demand therapy) when no erosive disease is present. 2, 6
• Reevaluate the need for continued PPI therapy within 12 months if GERD has never been objectively confirmed. 3, 2

When Dexlansoprazole May Be Considered

• If the patient has documented failure of twice-daily pantoprazole (or another first-line PPI) and endoscopy confirms Los Angeles Grade C or D erosive esophagitis, dexlansoprazole 60 mg once daily may be considered as a more potent alternative. 3, 4
• Dexlansoprazole's dual delayed-release formulation releases drug at two time points (1–2 hours and 4–5 hours post-administration), which may provide extended acid suppression. 7
• A 2024 meta-analysis demonstrated that dexlansoprazole outperformed placebo and other PPIs in resolution of heartburn and reflux symptoms, particularly in patients with moderate-to-severe symptoms. 8

Critical Pitfalls to Avoid

• Never prescribe PPIs to be taken at bedtime or randomly throughout the day, as proton pumps are not maximally activated during fasting or sleep states. 2
• Do not switch PPIs before escalating to twice-daily dosing of the initial agent, as this strategy is more evidence-based than agent-switching. 2
• Do not label treatment as failure at 4 weeks; some patients require the full 8-week course to achieve response. 6
• Avoid combining a PPI with an H₂-receptor antagonist as initial therapy; evidence does not support routine use of this combination for GERD. 6

Special Populations

Patients Taking Clopidogrel

• Pantoprazole is the preferred PPI for patients receiving clopidogrel because it exhibits minimal CYP2C19 inhibition and does not diminish clopidogrel's antiplatelet effect. 1, 6
• The American Heart Association and American College of Cardiology recommend avoiding omeprazole and esomeprazole in patients taking clopidogrel due to significant CYP2C19 inhibition. 1

Pediatric Patients (12–17 Years)

• Both dexlansoprazole and pantoprazole are FDA-approved for patients ≥12 years of age for healing erosive esophagitis and maintenance therapy. 4, 5
• Pantoprazole is also approved for children ≥5 years of age for short-term treatment of erosive esophagitis. 5

Hepatic Impairment

• For patients with moderate hepatic impairment (Child-Pugh Class B), dexlansoprazole dosing should be reduced to 30 mg once daily for healing erosive esophagitis. 4
• Dexlansoprazole is not recommended in severe hepatic impairment (Child-Pugh Class C). 4
• Pantoprazole can be used without dosage adjustment in patients with mild-to-moderate hepatic impairment. 9, 10

Safety Profile

• Both pantoprazole and dexlansoprazole share class-wide safety concerns, including possible increased risk of community-acquired pneumonia, Clostridioides difficile infection, and nutrient malabsorption with chronic use; however, these associations are likely attributable to residual confounding rather than direct causal effects. 1
• Common adverse effects include diarrhea, abdominal pain, nausea, upper respiratory infection, vomiting, and flatulence, occurring in ≤6% of patients. 7, 10
• Rebound acid hypersecretion (RAHS) may occur in patients discontinuing long-term PPI therapy, resulting from hypergastrinemia-induced parietal cell proliferation. 1