What is Aciphex (Rabeprazole)?
Aciphex (rabeprazole) is a proton pump inhibitor (PPI) that works by inhibiting gastric acid secretion through blocking the gastric H+, K+ATPase enzyme (proton pump) at the secretory surface of gastric parietal cells. 1
Mechanism of Action
Rabeprazole belongs to the class of proton pump inhibitors with these key characteristics:
- It inhibits the final step of gastric acid secretion by blocking the gastric H+, K+ATPase enzyme
- In the acidic environment of the stomach, rabeprazole is protonated and transformed into an active sulfenamide
- The antisecretory effect begins within one hour of oral administration
- A 20 mg dose inhibits basal and meal-stimulated acid secretion by 86% and 95% respectively 1
- It increases the percentage of time gastric pH remains above 3 from 10% to 65% 1
Clinical Uses
Rabeprazole is indicated for:
- Gastroesophageal reflux disease (GERD), both erosive and non-erosive forms 2
- Healing and maintenance of duodenal and gastric ulcers 3
- Part of combination therapy for Helicobacter pylori eradication 4
- Pathological hypersecretory conditions including Zollinger-Ellison syndrome 3
Pharmacological Properties
Rabeprazole has several unique properties compared to other PPIs:
- Faster onset of action due to its high pKa of approximately 5.0, allowing activation at higher pH levels 5
- Predominantly non-enzymatic metabolism, making it less susceptible to genetic variations in CYP2C19 enzymes 6
- Half-life of 1-2 hours, but with prolonged pharmacodynamic action due to sustained inactivation of the proton pump 1
- Acid-stable formulation that doesn't require conversion to an active form (not a prodrug) 2
Dosing Information
Standard dosing recommendations:
- 20 mg daily for 4 weeks for duodenal ulcers
- 20 mg daily for 6 weeks for gastric ulcers
- 20 mg daily for 8 weeks for GERD 7
- 10 or 20 mg daily for long-term maintenance of GERD healing 7
- For hypersecretory conditions, individualized dosing starting at 60 mg daily 7
Advantages Over Other Acid Suppressants
Rabeprazole offers several advantages:
- More potent acid suppression than histamine-2 receptor antagonists (H2RAs) 4
- Longer duration of action (24+ hours) compared to H2RAs (6 hours) 4
- Unlike H2RAs, rabeprazole doesn't develop tachyphylaxis (decreased effectiveness over time) 2
- Can be taken without regard to meal timing, unlike some other PPIs 2
Safety and Tolerability
Rabeprazole is generally well-tolerated:
- Most common adverse events include headache, rash, infection, diarrhea, and flu-like symptoms 7
- No dosage adjustment necessary in patients with renal impairment or mild to moderate hepatic impairment 8
- Low potential for drug interactions due to its predominantly non-enzymatic metabolism 3
Special Considerations
When prescribing rabeprazole, consider:
- In patients taking clopidogrel, rabeprazole (like other PPIs) may interfere with clopidogrel metabolism 2
- For pediatric patients 12-17 years old, the recommended dose is 20 mg daily 2
- The American Gastroenterological Association recommends regular review of ongoing indications for PPI use and considering dose reduction when possible 4
Rabeprazole represents an effective option for acid suppression with a rapid onset of action, consistent efficacy profile, and low drug interaction potential compared to other PPIs.