indication

For the treatment of acid-reflux disorders (GERD), peptic ulcer disease, H. pylori eradication, and prevention of gastroinetestinal bleeds with NSAID use.

pharmacology

Rabeprazole prevents the production of acid in the stomach. It reduces symptoms and prevents injury to the esophagus or stomach in patients with gastroesophageal reflux disease (GERD) or ulcers. Rabeprazole is also useful in conditions that produce too much stomach acid such as Zollinger-Ellison syndrome. Rabeprazole may also be used with antibiotics to get rid of bacteria that are associated with some ulcers. Rabeprazole is a selective and irreversible proton pump inhibitor, suppresses gastric acid secretion by specific inhibition of the H⁺, K⁺ -ATPase, which is found at the secretory surface of parietal cells. In doing so, it inhibits the final transport of hydrogen ions (via exchange with potassium ions) into the gastric lumen.

mechanism of action

Rabeprazole belongs to a class of antisecretory compounds (substituted benzimidazole proton-pump inhibitors) that do not exhibit anticholinergic or histamine H2-receptor antagonist properties, but suppress gastric acid secretion by inhibiting the gastric H⁺/K⁺ATPase (hydrogen-potassium adenosine triphosphatase) at the secretory surface of the gastric parietal cell. Because this enzyme is regarded as the acid (proton) pump within the parietal cell, rabeprazole has been characterized as a gastric proton-pump inhibitor. Rabeprazole blocks the final step of gastric acid secretion. In gastric parietal cells, rabeprazole is protonated, accumulates, and is transformed to an active sulfenamide. When studied in vitro, rabeprazole is chemically activated at pH 1.2 with a half-life of 78 seconds.

biotransformation

Hepatic

absorption

Absolute bioavailability is approximately 52%.

half life

1-2 hours (in plasma)

route of elimination

Following a single 20 mg oral dose of 14C-labeled rabeprazole, approximately 90% of the drug was eliminated in the urine, primarily as thioether carboxylic acid; its glucuronide, and mercapturic acid metabolites.

drug interactions

Atazanavir: Rabeprazole may decrease the serum levels and therapeutic effects of atazanavir.

Cefditoren: Proton pump inhibitors such as rabeprazole may decrease the serum concentration of cefditoren. If possible, avoid use of cefditoren with proton pump inhibitors (PPIs). Consider alternative methods to minimize/control acid reflux (eg, diet modification) or alternative antimicrobial therapy if use of PPIs can not be avoided.

Clopidogrel: Rabeprazole may decrease serum concentrations of the active metabolite(s) of clopidogrel. Due to the possible risk for impaired clopidogrel effectiveness with this combination, clinicians should carefully consider the need for concurrent rabeprazole therapy in patients receiving clopidogrel. Monitor response to clopidogrel closely when using clopidogrel with rabeprazole. Whether there are differences among individual proton pump inhibitors is unclear. Other acid-lowering therapies (e.g., H2-receptor antagonists, antacids, etc.) do not appear to share this interaction with clopidogrel.

Dasatinib: Rabeprazole may decrease the serum level of dasatinib.

Digoxin: Rabeprazole increases the effect of digoxin

Enoxacin: Rabeprazole may decrease the absorption of enoxacin.

Indinavir: Omeprazole decreases the absorption of indinavir

Itraconazole: The proton pump inhibitor, rabeprazole, may decrease the absorption of itraconazole.

Ketoconazole: The proton pump inhibitor, rabeprazole, may decrease the absorption of ketoconazole.

Tretinoin: The moderate CYP2C8 inhibitor, Rabaprazole, may decrease the metabolism and clearance of oral Tretinoin. Monitor for changes in Tretinoin effectiveness and adverse/toxic effects if Rabaprazole is initiated, discontinued to dose changed.