What are the recommended dosing regimens, contraindications, side effects, and alternative therapies for tegoprazan in adults?

Tegoprazan: Clinical Overview and Evidence-Based Recommendations

Overview and Mechanism

Tegoprazan is a potassium-competitive acid blocker (P-CAB) that provides rapid, potent, and prolonged gastric acid suppression through reversible ionic binding to the H+/K+-ATPase pump, independent of meal timing and CYP2C19 genetic polymorphisms 1.

Tegoprazan differs fundamentally from proton pump inhibitors (PPIs):

• Acid-stable (does not require enteric coating) 1
• Not a prodrug (no conversion needed for activation) 1
• Longer half-life (6-9 hours vs 1-2 hours for PPIs) 1
• Reversible binding to the proton pump 1
• Achieves maximal acid suppression within 1 day (vs 3-5 days for PPIs) 1
• Independent of CYP2C19 metabolism, eliminating pharmacokinetic variability seen with PPIs 1, 2

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Recommended Dosing Regimens

Erosive Esophagitis (Healing Phase)

• Tegoprazan 50 mg or 100 mg once daily for 4-8 weeks 3
• Both doses achieve 98.9% healing rates at 8 weeks, non-inferior to esomeprazole 40 mg 3
• Can be taken independent of meals (unlike PPIs which require premeal dosing) 1

Non-Erosive Reflux Disease (NERD)

• Tegoprazan 50 mg or 100 mg once daily for 4 weeks 4
• Complete symptom resolution rates: 42.5% (50 mg) and 48.5% (100 mg) vs 24.2% placebo 4
• Both doses superior to placebo (P = 0.0058 and P = 0.0004, respectively) 4

Gastric Ulcer Healing

• Tegoprazan 50-100 mg once daily for 8 weeks 1
• Healing rate: 95% vs 96% with lansoprazole 30 mg (non-inferior) 1

H. pylori Eradication

• Tegoprazan-based regimens are not specifically detailed in the provided evidence, though P-CABs as a class show superior eradication rates 1

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Clinical Positioning: When to Use Tegoprazan

NOT Recommended as First-Line Therapy

Tegoprazan should generally NOT be used as first-line therapy for peptic ulcer disease or routine GERD management 1. The 2024 AGA guideline emphasizes:

• Standard-dose PPIs remain first-line for most acid-related disorders due to established efficacy, extensive safety data, and lower cost 1
• Higher cost without clear superiority in mild-moderate disease limits first-line use 1

Appropriate Second-Line Use

Consider tegoprazan after PPI failure:

• Patients with erosive esophagitis who fail standard PPI therapy 1
• PPI-refractory ulcers (excluding those from malignancy, infection, vasculitis, or ischemia) 1

Specific Clinical Scenarios Where Tegoprazan May Be Preferred

1. Rapid acid suppression needed (e.g., acute bleeding ulcers requiring immediate control) 1
2. CYP2C19 poor metabolizers who respond inadequately to PPIs 1, 2
3. Patients requiring consistent acid suppression independent of meal timing 1

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Contraindications and Precautions

Drug Interactions

Tegoprazan is primarily metabolized by CYP3A4, creating significant drug-drug interaction potential 5:

• CYP3A4 inhibitors (e.g., clarithromycin): Increase tegoprazan AUC by 4.54-fold and Cmax by 2.05-fold 5
• CYP3A4 inducers (e.g., rifampicin): Decrease tegoprazan AUC by 5.71-fold and Cmax by 3.51-fold 5
• Dose adjustment required when co-administered with strong CYP3A4 perpetrators 5

Special Populations

• Hepatic impairment (Child-Pugh A): Standard dosing appropriate 6
• Severe renal impairment (eGFR <30 mL/min): Dose reduction recommended 6

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Side Effects and Safety Profile

Common Adverse Events

Tegoprazan is generally well-tolerated with a favorable safety profile 7, 4, 3:

• Gastrointestinal disorders: 2-4.9% (nausea, diarrhea) 2
• Headache: 1-4.9% 2
• Most adverse events are mild and resolve spontaneously without intervention 2

Comparative Safety

• Incidence of treatment-emergent adverse events comparable to placebo 4
• No significant safety differences compared to esomeprazole 40 mg 3
• Short-term safety comparable to PPIs, though long-term data are more limited 6

Theoretical Long-Term Concerns

• Serum gastrin elevation (2-3-fold higher than PPIs, but normalizes after discontinuation) 6
• Risk of Clostridioides difficile infection similar to PPIs 6
• Enterochromaffin-like cell hyperplasia rates similar to lansoprazole in 5-year data 6

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Alternative Therapies

Standard PPIs (First-Line Options)

Standard-dose PPIs remain the preferred initial therapy 1:

• Lansoprazole 30 mg, omeprazole 20 mg, esomeprazole 20 mg, or rabeprazole 20 mg once daily 8
• Lower cost and extensive safety data support first-line use 1

Escalation Strategy Before P-CABs

Before switching to tegoprazan, attempt:

1. Double-dose PPI regimen (e.g., lansoprazole 30 mg twice daily) 8, 6
2. Optimize PPI timing (30-60 minutes before meals) 1
3. Consider CYP2C19-guided PPI dosing in populations with high prevalence of poor metabolizers 8

Other P-CABs

• Vonoprazan: Superior for H. pylori eradication (92% vs 80% with PPIs) and severe erosive esophagitis maintenance 8, 6, 9
• Fexuprazan: Comparable acid inhibition to standard PPIs, not recommended as first-line 6

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Clinical Algorithm for Tegoprazan Use

For Erosive Esophagitis

1. Start with standard-dose PPI (e.g., esomeprazole 40 mg once daily) 1
2. If inadequate response after 4-8 weeks: Escalate to twice-daily PPI 8
3. If twice-daily PPI fails: Consider tegoprazan 50-100 mg once daily 1
4. Confirm failure objectively with endoscopy showing persistent LA grade B or greater erosions 8

For NERD

1. Start with standard-dose PPI for 4-8 weeks 1
2. If symptoms persist: Consider tegoprazan 50-100 mg once daily 4
3. Note: Evidence for tegoprazan in NERD shows modest benefit over placebo 4

For Peptic Ulcer Disease

1. Standard-dose PPI remains first-line 1
2. Reserve tegoprazan for PPI-refractory ulcers after excluding non-acid causes 1
3. Tegoprazan 50-100 mg once daily if used 1

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Common Pitfalls and How to Avoid Them

Pitfall 1: Using Tegoprazan as First-Line Therapy

• Avoid: Prescribing tegoprazan without attempting standard PPIs first 1, 6
• Solution: Reserve tegoprazan for documented PPI failures 1

Pitfall 2: Ignoring Drug Interactions

• Avoid: Co-prescribing with strong CYP3A4 inhibitors/inducers without dose adjustment 5
• Solution: Screen for clarithromycin, rifampicin, and other CYP3A4 perpetrators; adjust dose accordingly 5

Pitfall 3: Overlooking Cost Considerations

• Avoid: Prescribing tegoprazan when equally effective PPIs are available at lower cost 1, 6
• Solution: Use tegoprazan only when clinical superiority justifies higher expense 1

Pitfall 4: Failing to Confirm PPI Failure Objectively

• Avoid: Switching to tegoprazan based solely on patient-reported symptoms 8
• Solution: Obtain endoscopy or pH monitoring to document inadequate acid suppression before escalating 8

Pitfall 5: Assuming Greater Acid Suppression Equals Better Outcomes

• Avoid: Believing that more potent acid blockade automatically improves all foregut disorders 6
• Solution: Recognize that tegoprazan's superiority is condition-specific (e.g., severe erosive esophagitis, not mild GERD) 1

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Key Takeaways

• Tegoprazan provides rapid, potent, and consistent acid suppression independent of meals and CYP2C19 genetics 1, 7, 2
• Not recommended as first-line therapy for most acid-related disorders due to higher cost and lack of clear superiority over PPIs 1, 6
• Reserve for PPI failures, particularly in erosive esophagitis and peptic ulcer disease 1
• Monitor for CYP3A4 drug interactions and adjust dosing accordingly 5
• Safety profile comparable to PPIs in short-term studies, with most adverse events being mild and self-limiting 2, 4, 3