Rabeprazole

• GERD
• Peptic Ulcer Disease
• H. pylori Infection
• Zollinger-Ellison Syndrome

Rabeprazole is a proton pump inhibitor (PPI) that reduces gastric acid secretion. It is used to treat gastroesophageal reflux disease (GERD), peptic ulcer disease, and hypersecretory conditions.

Mechanism of Action

Rabeprazole suppresses gastric acid through irreversible enzyme inhibition:

• Prodrug activation: Converted to active sulfenamide form in acidic environment of parietal cells
• Irreversible H+/K+-ATPase inhibition: Covalently binds to cysteine residues on the proton pump
• Suppresses basal and stimulated acid: Blocks final common pathway of acid production
• Duration of effect: Acid suppression persists until new pumps are synthesized (24-48 hours)

Rabeprazole has the fastest onset among PPIs due to higher pKa and faster activation.

Available Formulations

• Delayed-release tablets: 20 mg
• Delayed-release sprinkle capsules: 5 mg, 10 mg (can be opened and sprinkled on soft food)

Tablets should be swallowed whole; do not crush or chew.

Medical Uses

FDA-Approved Indications:

• Healing of erosive or ulcerative GERD
• Maintenance of healing of erosive GERD
• Symptomatic GERD
• Healing of duodenal ulcers
• Helicobacter pylori eradication (combination therapy)
• Pathological hypersecretory conditions including Zollinger-Ellison syndrome

Dosing Guidelines

Erosive GERD:

• Adults: 20 mg once daily for 4-8 weeks
• Maintenance: 20 mg once daily
• Adolescents ≥12 years: 20 mg once daily for up to 8 weeks

Symptomatic GERD:

• 20 mg once daily for 4 weeks

Duodenal Ulcer:

• 20 mg once daily after morning meal for up to 4 weeks

H. pylori Eradication:

• 20 mg twice daily with amoxicillin and clarithromycin for 7 days

Zollinger-Ellison Syndrome:

• Start 60 mg once daily; adjust based on response
• Doses up to 100 mg daily or 60 mg twice daily have been used

Important Safety Information

Warnings and Precautions:

• Clostridium difficile-associated diarrhea: Increased risk with PPI use
• Bone fractures: Long-term use associated with increased hip, wrist, and spine fractures
• Hypomagnesemia: May occur with prolonged use; monitor magnesium levels
• Vitamin B12 deficiency: Long-term acid suppression may reduce absorption
• Fundic gland polyps: Risk increases with long-term use
• Acute interstitial nephritis: May occur at any time during therapy
• Cutaneous and systemic lupus erythematosus: Has been reported

Contraindications:

• Known hypersensitivity to rabeprazole, substituted benzimidazoles, or any component
• Concomitant use with rilpivirine-containing products

Drug Interactions

• Rilpivirine: Contraindicated (reduced rilpivirine absorption)
• Methotrexate: May increase methotrexate levels (especially high doses)
• Clopidogrel: Less interaction than with some other PPIs (rabeprazole minimally affects CYP2C19)
• Drugs requiring acidic pH for absorption: May reduce absorption (ketoconazole, iron, digoxin)
• Warfarin: Monitor INR
• Tacrolimus: May increase tacrolimus levels

Special Populations

• Hepatic Impairment:
  • Mild to moderate: No adjustment
  • Severe: Use with caution (limited data)
• Renal Impairment: No adjustment needed
• Elderly: No adjustment needed
• Pregnancy: Limited data; use only if benefit outweighs risk
• Pediatric: Approved for GERD in patients ≥12 years (tablets), ≥1 year (sprinkle capsules)