Vonoprazan + Amoxicillin + Clarithromycin

• Eradication of Helicobacter pylori infection, associated with:
• Peptic ulcer disease (gastric and duodenal ulcers)
• Chronic gastritis
• Prevention of ulcer recurrence in H. pylori-positive patients
• Gastric mucosa-associated lymphoid tissue (MALT) lymphoma in H. pylori-positive patients
• Off-label uses (clinically accepted):
• Management of refractory H. pylori infection
• Functional dyspepsia associated with H. pylori infection

Adults:

• Vonoprazan 20 mg orally twice daily
• Amoxicillin 750 mg orally twice daily
• Clarithromycin 200 mg orally twice daily
• Duration: 7 to 14 days (commonly 7 days)

Special Populations:

• Elderly: Same dosing unless renal impairment present
• Renal impairment: Adjust amoxicillin dose based on creatinine clearance; vonoprazan and clarithromycin generally no adjustment unless severe impairment
• Hepatic impairment: Use with caution; clarithromycin dose adjustment may be required
• Pediatrics: Safety and efficacy not established; use not generally recommended

Administration:

• Oral route
• Can be taken with or without food, preferably consistently
• Complete full course even if symptoms improve

Vonoprazan is a potassium-competitive acid blocker (P-CAB) that inhibits the gastric H+/K+-ATPase enzyme in parietal cells, leading to rapid and potent suppression of gastric acid secretion. This elevated gastric pH enhances the effectiveness of antibiotics against H. pylori. Amoxicillin is a beta-lactam antibiotic that inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins, causing bacterial cell death. Clarithromycin, a macrolide antibiotic, inhibits bacterial protein synthesis by binding to the 50S ribosomal subunit, preventing bacterial growth. Together, these actions effectively eradicate H. pylori infection.

• Vonoprazan:
• Absorption: Rapid oral absorption, peak plasma concentration in ~2 hours
• Bioavailability: High, not significantly affected by food
• Half-life: Approximately 7.7 hours
• Metabolism: Mainly hepatic via CYP3A4
• Excretion: Primarily fecal and renal
• Amoxicillin:
• Absorption: Well absorbed orally, peak in 1-2 hours
• Bioavailability: 75–90%
• Half-life: About 1 hour (normal renal function)
• Metabolism: Minimal hepatic
• Excretion: Renal, mainly unchanged
• Clarithromycin:
• Absorption: Well absorbed, peak plasma concentration in 2-3 hours
• Bioavailability: About 50% due to first-pass metabolism
• Half-life: Parent drug 3-4 hours; active metabolite 14-19 hours
• Metabolism: Extensive hepatic metabolism by CYP3A4
• Excretion: Renal and fecal

• Pregnancy:
• Vonoprazan: Limited human data; animal studies show no clear teratogenic risk but caution advised
• Amoxicillin: Generally considered safe (FDA Category B)
• Clarithromycin: Use avoided unless clearly necessary (FDA Category C) due to limited human data
• Lactation:
• Vonoprazan: Unknown if excreted in human milk; caution advised
• Amoxicillin: Excreted in breast milk in low amounts; generally safe
• Clarithromycin: Excreted in breast milk; potential for infant adverse effects; weigh risks and benefits

• Vonoprazan: Potassium-competitive acid blocker (P-CAB)
• Amoxicillin: Beta-lactam antibiotic (Penicillin class)
• Clarithromycin: Macrolide antibiotic

• Hypersensitivity to vonoprazan, amoxicillin, clarithromycin, or related antibiotics
• History of cholestatic jaundice or hepatic dysfunction with clarithromycin
• Severe hepatic impairment (due to clarithromycin)
• Use with drugs that are contraindicated due to CYP3A4 interactions with clarithromycin
• Known QT prolongation or cardiac arrhythmias (due to clarithromycin)

• Use caution in severe renal or hepatic impairment
• Monitor for Clostridioides difficile-associated diarrhea
• Clarithromycin may prolong QT interval; monitor cardiac patients closely
• Risk of hypersensitivity and severe skin reactions
• Complete full antibiotic course to reduce resistance risk
• Monitor for early signs of hepatotoxicity and allergic reactions

• Common: Diarrhea, nausea, abdominal pain, altered taste, headache, dizziness, rash
• Serious but rare: Clostridioides difficile-associated diarrhea, hepatotoxicity, QT prolongation, severe allergic reactions including anaphylaxis and Stevens-Johnson syndrome

• Clarithromycin is a strong CYP3A4 inhibitor; may increase levels and toxicity of many drugs (e.g., statins, benzodiazepines, calcium channel blockers)
• Vonoprazan is metabolized by CYP3A4; interactions possible with CYP3A4 inhibitors or inducers
• Amoxicillin may slightly reduce efficacy of oral contraceptives
• Avoid combining clarithromycin with other QT-prolonging drugs
• Alcohol may exacerbate gastrointestinal irritation and reduce therapy efficacy

• Vonoprazan-based triple therapy increasingly preferred for H. pylori eradication due to superior acid suppression and higher eradication rates compared to PPI-based therapy
• Recommended treatment duration remains 7 to 14 days based on regional resistance patterns
• Updated cardiac risk warnings for clarithromycin usage
• Recognized by WHO and major gastroenterology societies as effective first-line therapy in many countries

• Store at 20°C to 25°C (68°F to 77°F)
• Protect from moisture and light
• Keep in original packaging until use
• Do not freeze
• Keep out of reach of children