Rabeprazole + Amoxicillin + Clarithromycin

Approved Indications

• Eradication of Helicobacter pylori infection in patients with:
• Active duodenal ulcer
• Active gastric ulcer
• History of peptic ulcer disease
• Chronic gastritis associated with H. pylori
  This triple therapy is approved to reduce the risk of ulcer recurrence associated with H. pylori infection.

Clinically Accepted Off-Label Uses

• Non-ulcer dyspepsia (biopsy-confirmed H. pylori)
• MALT lymphoma (gastric marginal zone lymphoma linked to H. pylori)
• Prevention of recurrent peptic ulcer bleeding in H. pylori-positive patients
• Initial therapy in geographical regions with low clarithromycin resistance (<15%)

Adults (Standard Regimen)

• Rabeprazole sodium 20 mg, Amoxicillin 1000 mg, Clarithromycin 500 mg:
  Orally twice daily for 14 days

Pediatric Use

• Not routinely recommended due to limited data on safety and efficacy in children under 12 years

Elderly

• Use adult dosage; assess renal and hepatic function
• Monitor for antibiotic-associated diarrhea and cardiac conduction abnormalities

Renal Impairment

• Amoxicillin: Dose adjustment required if CrCl <30 mL/min
• Clarithromycin: Dose adjustment needed if CrCl <30 mL/min; avoid if severe renal and hepatic impairment coexist
• Rabeprazole: No adjustment necessary

Hepatic Impairment

• Rabeprazole: No adjustment for mild to moderate dysfunction
• Clarithromycin: Use with caution in moderate to severe hepatic impairment
• Amoxicillin: No specific adjustment required

Administration Tips

• Take doses after meals for better tolerance and efficacy
• Swallow tablets/capsules whole with water
• Do not crush or chew

• Rabeprazole inhibits the H⁺/K⁺-ATPase enzyme system (proton pump) in gastric parietal cells, blocking acid secretion and increasing gastric pH, which enhances antibiotic stability and efficacy.
• Amoxicillin binds to penicillin-binding proteins in H. pylori, disrupting bacterial cell wall synthesis and causing cell lysis.
• Clarithromycin inhibits bacterial protein synthesis by binding to the 50S ribosomal subunit, thus exerting a bacteriostatic effect against H. pylori.

Combined, these agents eradicate H. pylori by acid suppression (Rabeprazole) and dual antibacterial action (Amoxicillin and Clarithromycin), leading to ulcer healing and reduced recurrence.

Rabeprazole

• Absorption: Rapid; peak concentration ~3.5 hours
• Bioavailability: ~52%, not affected by food
• Metabolism: Liver (non-CYP and CYP3A4/CYP2C19 pathways)
• Half-life: ~1–2 hours
• Excretion: Urine and feces (mostly as metabolites)

Amoxicillin

• Absorption: High (~90%)
• Metabolism: Minimal hepatic metabolism
• Half-life: ~1.5 hours
• Excretion: Primarily via urine (60–70% unchanged)

Clarithromycin

• Absorption: Moderate (~50%)
• Metabolism: Hepatic via CYP3A4; active metabolite (14-hydroxy-clarithromycin)
• Half-life: ~3–7 hours (longer with renal impairment)
• Excretion: Urine (~40%) and feces (~40%)

Pregnancy

• Rabeprazole: Category B – Safe in animals, no well-controlled human studies
• Amoxicillin: Category B – Safe in pregnancy, widely used
• Clarithromycin: Category C – Teratogenic effects in animals; use only if benefits outweigh risks

Lactation

• Rabeprazole: Unknown excretion in human milk; caution advised
• Amoxicillin: Excreted in breast milk; usually safe, monitor infant for diarrhea or rash
• Clarithromycin: Excreted in milk; may cause GI effects or sensitization in infant – use with caution

• Rabeprazole: Proton Pump Inhibitor (PPI)
• Amoxicillin: Penicillin-class Beta-lactam Antibiotic
• Clarithromycin: Macrolide Antibiotic
• Combination Use: Anti-H. pylori triple therapy regimen

• Hypersensitivity to rabeprazole, penicillins (amoxicillin), or macrolides (clarithromycin)
• History of anaphylaxis or severe allergy to any component
• Concomitant use of clarithromycin with:
• Cisapride
• Pimozide
• Ergot derivatives
• Severe renal impairment (CrCl <30 mL/min) without dose adjustment
• History of cholestatic jaundice or hepatic dysfunction due to clarithromycin

• Cardiac Risk (Clarithromycin):
• May cause QT prolongation, ventricular arrhythmias, including torsades de pointes
• Avoid in patients with existing QT prolongation or those taking other QT-prolonging agents
• Hepatotoxicity:
• Clarithromycin may cause elevated liver enzymes, hepatitis, or cholestatic jaundice
• C. difficile-Associated Diarrhea (CDAD):
• Risk with broad-spectrum antibiotics (amoxicillin, clarithromycin)
• Allergic Reactions (Amoxicillin):
• Risk of severe hypersensitivity, including anaphylaxis and Stevens-Johnson syndrome
• PPI Long-Term Use (Rabeprazole):
• Risk of hypomagnesemia, osteoporotic fractures, B12 deficiency
• Monitor renal and hepatic function in elderly or compromised patients

Common Side Effects

• Gastrointestinal: Nausea, vomiting, abdominal pain, diarrhea, dysgeusia (altered taste)
• Neurologic: Headache, dizziness
• Skin: Rash, pruritus
• General: Flatulence, fatigue

Serious Side Effects

• Cardiac: QT prolongation, arrhythmias (Clarithromycin)
• Hepatic: Cholestatic hepatitis, elevated transaminases (Clarithromycin)
• Hematologic: Thrombocytopenia, leukopenia (rare)
• Hypersensitivity: Anaphylaxis, angioedema (Amoxicillin)
• CNS (high-dose clarithromycin): Confusion, hallucinations (rare)
• Renal: Interstitial nephritis (Amoxicillin – rare)

• Clarithromycin:
• Inhibits CYP3A4 – increases serum levels of statins, benzodiazepines, carbamazepine, theophylline, and warfarin
• ↑ Risk of arrhythmias with QT-prolonging drugs (e.g., amiodarone, sotalol)
• Rabeprazole:
• May ↓ absorption of drugs needing acidic environment (e.g., ketoconazole, itraconazole)
• Caution with clopidogrel – may reduce antiplatelet effect
• Amoxicillin:
• ↓ Efficacy of oral contraceptives
• ↑ Risk of rash with allopurinol
• May antagonize effects of bacteriostatic antibiotics (e.g., tetracyclines)
• Alcohol:
• No direct interaction but may worsen GI side effects or liver stress

• ACG Guidelines (2022):
• Clarithromycin-based triple therapy only recommended if local clarithromycin resistance <15%
• Maastricht VI/Florence Consensus (2022):
• 14-day duration preferred for higher eradication rates
• Alternative regimens (bismuth quadruple or sequential therapy) favored in high-resistance regions
• FDA Update:
• Strengthened clarithromycin warnings regarding cardiovascular mortality in patients with heart disease
• Emphasis on QT risk and hepatic monitoring

Individual Drug Storage

• Rabeprazole:
• Store at 20°C to 25°C (68°F to 77°F)
• Protect from light and moisture
• Amoxicillin:
• Store at 15°C to 30°C (59°F to 86°F)
• Protect from excessive heat and humidity
• Clarithromycin:
• Store at 20°C to 25°C
• Protect from light and moisture

General Handling Notes

• Keep in original packaging
• Do not freeze
• Keep out of reach of children
• Follow specific manufacturer instructions for co-packaged kits