Introduction
Rabeprazole is a proton pump inhibitor (PPI) that suppresses gastric acid secretion by inhibiting the H+/K+ ATPase enzyme system at the secretory surface of gastric parietal cells. It is commonly prescribed for acid-related gastrointestinal disorders and belongs to the benzimidazole class of PPIs alongside omeprazole, lansoprazole, and pantoprazole.
Mechanism of Action
Rabeprazole is a prodrug that undergoes activation in the acidic environment of parietal cells. It is converted to its active form (sulfenamide) which forms covalent disulfide bonds with cysteine residues on the H+/K+ ATPase proton pump. This irreversible inhibition effectively blocks the final step of gastric acid production, leading to prolonged suppression of both basal and stimulated acid secretion. The antisecretory effect begins within one hour and reaches its maximum after 2-4 hours of oral administration.
Indications
- Healing and maintenance of erosive or ulcerative gastroesophageal reflux disease (GERD)
- Symptomatic GERD
- Healing of duodenal ulcers
- Healing of gastric ulcers
- Treatment of pathological hypersecretory conditions including Zollinger-Ellison syndrome
- Helicobacter pylori eradication in combination with antibiotics (typically amoxicillin and clarithromycin)
Dosage and Administration
Standard adult dosing:- GERD: 20 mg once daily for 4-8 weeks
- Maintenance therapy for GERD: 20 mg once daily
- Duodenal ulcers: 20 mg once daily after morning meal for 4 weeks
- Gastric ulcers: 20 mg once daily for up to 8 weeks
- Hypersecretory conditions: Initial 60 mg once daily, may increase to 100 mg daily in divided doses
- H. pylori eradication: 20 mg twice daily with amoxicillin 1000 mg twice daily and clarithromycin 500 mg twice daily for 7-14 days
- Hepatic impairment: Consider dose reduction in severe cirrhosis
- Renal impairment: No dose adjustment required
- Geriatric patients: No dose adjustment required
- Pediatric patients: Safety and efficacy not established for children under 12
- Should be taken before meals, typically before breakfast
- Swallow tablets whole; do not crush, chew, or split
- Delayed-release formulation protects the drug from gastric acid degradation
Pharmacokinetics
Absorption: Rapidly absorbed from the gastrointestinal tract with mean bioavailability of approximately 52%. Food may delay absorption but does not significantly affect overall bioavailability. Distribution: Approximately 96% plasma protein bound. Volume of distribution is 0.34 L/kg. Metabolism: Extensively metabolized in the liver primarily via non-enzymatic reduction to thioether rabeprazole and via cytochrome P450 system (CYP3A4 and CYP2C19 isoenzymes) to desmethyl rabeprazole and rabeprazole sulfone. Elimination: Primarily renal excretion (90%) as metabolites. Elimination half-life is approximately 1 hour. Total body clearance is 4.4 L/h.Contraindications
- Known hypersensitivity to rabeprazole, substituted benzimidazoles, or any component of the formulation
- Concomitant use with rilpivirine-containing products due to potential for reduced antiviral efficacy
- Patients taking atazanavir or nelfinavir (significant reduction in antiretroviral concentrations)
Warnings and Precautions
- Clostridium difficile-associated diarrhea: PPIs may increase risk
- Bone fracture: Long-term and high-dose therapy may increase risk of osteoporosis-related fractures of hip, wrist, or spine
- Hypomagnesemia: Reported with prolonged PPI use; monitor magnesium levels
- Vitamin B12 deficiency: Long-term use may be associated with decreased vitamin B12 absorption
- Acute interstitial nephritis: Has been observed with PPIs; discontinue if suspected
- Cutaneous and systemic lupus erythematosus: New onset or exacerbation reported
- Fundic gland polyps: Long-term use associated with increased risk
Drug Interactions
- Atazanavir: Rabeprazole significantly reduces atazanavir concentrations
- Warfarin: Monitor INR due to potential increased anticoagulant effect
- Methotrexate: May decrease methotrexate clearance
- Digoxin: Possible increased digoxin absorption
- Ketoconazole, itraconazole: Decreased absorption of these drugs due to increased gastric pH
- Clopidogrel: Theoretical interaction due to CYP2C19 inhibition (clinical significance uncertain)
- CYP2C19 substrates: Potential increased concentrations of drugs metabolized by this enzyme
Adverse Effects
Common (≥1%):- Headache
- Diarrhea
- Nausea
- Abdominal pain
- Flatulence
- Constipation
- Dry mouth
- Dizziness
- Anaphylaxis
- Stevens-Johnson syndrome
- Toxic epidermal necrolysis
- Acute interstitial nephritis
- Hepatitis
- Pancreatitis
- Hypomagnesemia
- Clostridium difficile-associated diarrhea
- Bone fracture
Monitoring Parameters
- Symptom improvement and resolution
- Magnesium levels with prolonged therapy (≥3 months) or concomitant diuretic use
- Vitamin B12 levels with long-term therapy (>2-3 years)
- Bone density assessment in patients with risk factors for osteoporosis on long-term therapy
- Renal function in patients with suspected interstitial nephritis
- Complete blood count if clinical signs of bleeding
- Monitoring for signs of C. difficile infection with persistent diarrhea
Patient Education
- Take medication 30 minutes before breakfast for optimal effect
- Swallow tablets whole; do not crush or chew
- Report any signs of bleeding (black stools, coffee-ground emesis)
- Report persistent diarrhea, abdominal pain, or fever
- Long-term use may require monitoring for bone health and nutrient deficiencies
- Do not discontinue abruptly without medical supervision
- Inform all healthcare providers about rabeprazole use, especially before new prescriptions
- Be aware of potential interactions with other medications
- Report any new skin rashes or joint pain
References
1. Shirai N, Furuta T, Moriyama Y, et al. Effects of CYP2C19 genotypic differences in the metabolism of omeprazole and rabeprazole on intragastric pH. Aliment Pharmacol Ther. 2001;15(12):1929-1937. 2. Prakash A, Faulds D. Rabeprazole. Drugs. 1998;55(2):261-267. 3. FDA Prescribing Information: AcipHex (rabeprazole sodium). Revised 2022. 4. Katz PO, Dunbar KB, Schnoll-Sussman FH, et al. ACG Clinical Guideline for the Diagnosis and Management of Gastroesophageal Reflux Disease. Am J Gastroenterol. 2022;117(1):27-56. 5. Chey WD, Leontiadis GI, Howden CW, Moss SF. ACG Clinical Guideline: Treatment of Helicobacter pylori Infection. Am J Gastroenterol. 2017;112(2):212-239. 6. Moayyedi P, Eikelboom JW, Bosch J, et al. Safety of Proton Pump Inhibitors Based on a Large, Multi-Year, Randomized Trial of Patients Receiving Rivaroxaban or Aspirin. Gastroenterology. 2019;157(3):682-691. 7. Strand DS, Kim D, Peura DA. 25 Years of Proton Pump Inhibitors: A Comprehensive Review. Gut Liver. 2017;11(1):27-37.