Pharmacology Update
Rabeprazole Delayed Release Tablets (Aciphex—Eisai Inc. and Janssen Pharmaceutica)
By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD
The fda has approved a third proton pump inhibitor (PPI) for the treatment of duodenal ulcers and gastroesophageal reflux disease (GERD). Rabeprazole (Aciphex) joins omeprazole (Prilosec) and lansoprazole (Prevacid) in this competitive, $3 billion worldwide market. Rabeprazole will be comarketed in this country by Eisai Inc and Janssen Pharmaceutica. The drug is a pyridyl methysulfinyl benzaminidazole, chemically similar to omeprazole. The PPIs inhibit gastric acid secretion by inhibiting the proton pump (H+/K+ ATPase) in the canalicular membrane of gastric parietal cells.1
Indications
Rabeprazole is approved for the healing of duodenal ulcers and erosive or ulcerative gastroesophageal reflux disease (GERD). It is also indicated for the maintenance or healing of erosive or ulcerative GERD and the treatment of pathological hypersecretory conditions (e.g., Zollinger-Ellison syndrome).
Dosage
For duodenal ulcers, rabeprazole is dosed at 20 mg once daily after the morning meal for up to four weeks (a few patients may require longer therapy). The same dose is given for erosive or ulcerative gastrointestinal reflux disease, 20 mg once daily, but for 4-8 weeks. If healing has not been achieved, an additional eight-week course may be considered. A dose of 20 mg once daily may also be given long term for maintenance or healing of erosive or ulcerative gastrointestinal reflux disease. Higher doses are required for pathological hypersecretory conditions: 60 mg once daily initially with dosage and duration adjustments as appropriate up to 100 mg daily or 60 mg twice daily.6
The tablets should be taken whole and not chewed, crushed, or split. No dosage adjustment is necessary in the elderly, patients with renal impairment, or patients with mild to moderate hepatic impairment. Rabeprazole is supplied as 20 mg delayed-release enteric coated tablets.
Potential Advantages
In two European comparative trials between rabeprazole (20 mg daily) and omeprazole (20 mg daily), one with gastric ulcer (n = 227) and one with duodenal ulcer (n = 205), the rabeprazole treated groups had a significantly higher percentage of patients showing improvement in daytime pain symptom relief at the three- or four-week end point respectively, but no difference in healing rates.4,5 In addition to daytime pain symptom relief, rabeprazole-treated patients with gastric ulcers also had a significantly higher percentage of patients reporting reduction in pain frequency and complete resolution of night pain at six weeks.4 Symptom improvements are secondary end points based on patient diaries using five-point scales.4,5
Clinically significant drug interactions involving the cytochrome P450 system have not been reported with rabeprazole even though the drug is metabolized by this enzyme system.6
Rabeprazole has been shown in animal studies to increase mucin synthesis in gastric mucosa, while omeprazole decreases synthesis and lansoprazole has no effect.2 Rabeprazole has also been reported to have greater antimicrobial activity against H. pylori than omeprazole and lansoprazole.2 Rabeprazole is apparently a noncompetitive irreversible inhibitor for bacterial urease.3
Potential Disadvantages
Rabeprazole decreases the bioavailability of ketoconazole and coadministration is not recommended.2 Headache is the most commonly reported side effect with an incidence of 2.4% vs. 1.6% for placebo.6 Rabeprazole has not been approved by the FDA for the treatment of gastric ulcers.
Comments
Rabeprazole is a potent proton pump inhibitor similar to omprazole and lansoprazole. It differs from these other agents by being a "reversible" inhibitor that results in shorter duration of action.2 The duration of action is about two days for rabeprazole compared to four days for omeprazole.2 Clinical trials indicate that rabeprazole was reported to be well tolerated and as efficacious as omeprazole and more efficacious than ranitidine in promoting the healing of erosive or ulcerative gastrointestinal reflux disease (GERD).7,9 The drugs were comparable in relief of heartburn symptoms.5 Rabeprazole and omeprazole also produced comparable healing in duodenal and gastric ulcers, although certain symptom relief end points were reported to be in favor of rabeprazole.4,5 Rabeprazole has also been reported to be effective when used in combination with antibiotics for the eradication of H. pylori.8
The cost of rabeprazole is slightly less than that of omeprazole ($3.70 vs $3.99) and similar to that of lansoprazole 15 mg ($3.66) and lansoprazole 30 mg ($3.73).
Clinical Implications
Rabeprazole provides an alternative to omeprazole and lansoprazole. Results from clinical trials suggest that rabeprazole may provide better symptom relief than omeprazole in patients with duodenal or gastric ulcers. However, these were observed for only certain secondary symptom end points, one out of six for duodenal ulcers and three out of six for gastric ulcers. In addition, no differences were reported for patients with GERD.
Which of the following has been reported to have greater antimicrobial activity against H. pylori?
a. Omeprazole
b. Lansoprazole
c. Rabeprazole
d. None of the above
References
1. Richardson P, et al. Drugs 1998;56(3):307-335.
2. Praash A, et al. Drugs 1998;55(2):261-267.
3. Park JE, et al. Biol Pharm Bull 1996;19:182-187.
4. Dekkers CP, et al. Aliment Pharmacol Ther 1998; 12(8):789-795.
5. Dekkers CP, et al. Aliment Pharmacol Ther 1999; 13(2):179-186.
6. Aciphex Product Information. Eisai Inc. and Janssen Pharmaceutica. August 1999.
7. Dekkers CP, et al. Aliment Pharmacol Ther 1999; 13(1):49-57.
8. Stack WA, et al. Am J Gastroenterol 1998;93(10): 1909-1913.
9. Humphries TJ, et al. Gastroenterology 1997; 112(4):A154 (abstract).
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