Rabeprazole
Rabeprazole
Generic Name
Rabeprazole
Mechanism
Rabeprazole irreversibly inhibits the H⁺/K⁺‑ATPase enzyme (the proton pump) located on the luminal surface of gastric parietal cells.
• Selective binding: It forms a covalent thioether bond with the cysteine residue of the pump.
• Permanent inactivation: The pumped‑up enzyme cannot be reactivated until a new pump is synthesized, yielding a prolonged acid‑suppression effect.
• Rapid onset: Peak inhibition occurs within 1–2 hours after dosing.
Pharmacokinetics
- Absorption: Oral tablets or delayed‑release capsules are absorbed in the small intestine; peak plasma concentration tₘₐₓ ≈ 1.5–2 h.
- Distribution: Highly protein‑bound (> 90 %); volume of distribution ≈ 25 L.
- Metabolism: Primarily hepatic via CYP2C19 (major) and CYP3A4; minor glucuronidation.
- Half‑life: Apparent terminal half‑life ≈ 1.5–2 h, but the pharmacodynamic effect lasts >24 h because of irreversible pump inhibition.
- Excretion: Renal (≈ 45 %) and fecal (≈ 55 %) routes; unchanged drug in urine ~4–7 %.
Indications
- GERD (reflux esophagitis, erosive esophagitis, heartburn).
- Helicobacter pylori eradication (*rabeprazole* ± amoxicillin + clarithromycin) for 7–14 days.
- Peptic ulcer disease (gastric and duodenal ulcers).
- Zollinger–Ellison syndrome (acutely).
- Prevention of NSAID‑associated ulcers in high‑risk patients.
- Acid‑related GI bleeding (stabilization and reduction of rebleeding risk).
Contraindications
| Category | Key Points |
| Contraindications | Hypersensitivity to rabeprazole or any of its excipients. |
| Warnings |
• Long‑term use (>12 months) may increase risk of *osteoporosis‑related fractures*, *Clostridioides difficile* infection, and *hypomagnesemia*. • Chronic suppression may mask gastritis or gastric cancer; routine surveillance recommended in high‑risk patients. • Co‑administration with clopidogrel may reduce antiplatelet effect (see drug interactions). |
| Precautions |
• Renal impairment: Dose adjustment unnecessary for mild–moderate CKD; monitor in severe CKD. • Hepatic disease: Dose adjustment not required; monitor liver function tests. |
Dosing
| Indication | Dose | Schedule | Administration Notes |
| GERD, ulcers | 20 mg | Once daily, before the main meal (≥ 30 min). | Can be given with or without food. |
| H. pylori eradication | 20 mg | BID (every 12 h) or 20 mg QD | Use 7–14 days with amoxicillin ± clarithromycin/metronidazole. |
| Zollinger–Ellison | 40 mg | Once daily | For acute severe acid overload. |
| NSAID ulcer prophylaxis | 20 mg | Once daily | During NSAID therapy for ≥4 weeks. |
• Delayed‑release formulation: Place capsule on the tongue or swallow whole; do not crush or chew.
• Storage: Store at room temperature (15–25 °C); avoid extreme heat or moisture.
Adverse Effects
- Common (≥ 2 %): nausea, abdominal pain, diarrhea, headache, flatulence, insomnia, dyspepsia.
- Less common (< 2 %): dizziness, rash, pruritus, alopecia.
- Serious (rare): interstitial nephritis, hypomagnesemia, hepatic transaminosis, thrombocytopenia, *Clostridioides difficile* colitis, pulmonary thromboembolism, PJP pneumonia (in immunocompromised).
Monitoring
- Baseline: CBC, serum electrolytes (magnesium), liver enzymes, creatinine.
- During therapy:
- Magnesium: Check every 3–6 months if on >2 months of therapy, or earlier if symptoms of hypomagnesemia.
- Vitamin B12: Assess if therapy >12 months or in patients with malabsorption.
- Bone density: In patients >70 y, long‑term use >12 months, or those on steroids.
- Drug interactions: Review concomitant medications (e.g., clopidogrel, atazanavir).
Clinical Pearls
- Rapid acid suppression: Rabeprazole reaches therapeutic plasma levels faster than some other PPIs (3 months of use).
For optimal patient outcomes, tailor rabeprazole dosing to the specific indication, adjust based on renal/hepatic function, and remain vigilant for drug–drug interactions and metabolic complications.