Aciphex - General Information
Aciphex is an antiulcer drug in the class of proton pump inhibitors. It is a prodrug - in the acid environment of the parietal cells it turns into active sulphenamide form. Aciphex inhibits the H+, K+ATPase of the coating gastric cells and dose-dependent oppresses basal and stimulated gastric acid secretion.
Pharmacology of Aciphex
Aciphex 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. Aciphex is also useful in conditions that produce too much stomach acid such as Zollinger-Ellison syndrome. Aciphex may also be used with antibiotics to get rid of bacteria that are associated with some ulcers. Aciphex is a selective and irreversible proton pump inhibitor, suppresses gastric acid secretion by specific inhibition of the H+, K+ -ATPase enzyme system which is found at the secretory surface of parietal cells. It inhibits the final transport of hydrogen ions (via exchange with potassium ions) into the gastric lumen.
Aciphex for patients
Patients should be cautioned that ACIPHEX® delayed-release tablets should be swallowed whole. The tablets should not be chewed, crushed, or split. ACIPHEX® can be taken with or without food.
Rabeprazole is metabolized by the cytochrome P450 (CYP450) drug metabolizing enzyme system. Studies in healthy subjects have shown that rabeprazole does not have clinically significant interactions with other drugs metabolized by the CYP450 system, such as warfarin and theophylline given as single oral doses, diazepam as a single intravenous dose, and phenytoin given as a single intravenous dose (with supplemental oral dosing). Steady state interactions of rabeprazole and other drugs metabolized by this enzyme system have not been studied in patients. There have been reports of increased INR and prothrombin time in patients receiving proton pump inhibitors, including rabeprazole, and warfarin concomitantly. Increases in INR and prothrombin time may lead to abnormal bleeding and even death.
In vitro incubations employing human liver microsomes indicated that rabeprazole inhibited cyclosporine metabolism with an IC50 of 62 micromolar, a concentration that is over 50 times higher than the Cmax in healthy volunteers following 14 days of dosing with 20 mg of rabeprazole. This degree of inhibition is similar to that by omeprazole at equivalent concentrations.
Rabeprazole produces sustained inhibition of gastric acid secretion. An interaction with compounds which are dependent on gastric pH for absorption may occur due to the magnitude of acid suppression observed with rabeprazole. For example, in normal subjects, co-administration of rabeprazole 20 mg QD resulted in an approximately 30% decrease in the bioavailability of ketoconazole and increases in the AUC and Cmax for digoxin of 19% and 29%, respectively. Therefore, patients may need to be monitored when such drugs are taken concomitantly with rabeprazole. Co-administration of rabeprazole and antacids produced no clinically relevant changes in plasma rabeprazole concentrations.
In a clinical study in Japan evaluating rabeprazole in patients categorized by CYP2C19 genotype (n=6 per genotype category), gastric acid suppression was higher in poor metabolizers as compared to extensive metabolizers. This could be due to higher rabeprazole plasma levels in poor metabolizers. Whether or not interactions of rabeprazole sodium with other drugs metabolized by CYP2C19 would be different between extensive metabolizers and poor metabolizers has not been studied.
Combined Administration with Clarithromycin
Combined administration consisting of rabeprazole, amoxicillin, and clarithromycin resulted in increases in plasma concentrations of rabeprazole and 14-hydroxyclarithromycin.
Concomitant administration of clarithromycin with pimozide and cisapride is contraindicated.
Rabeprazole is contraindicated in patients with known hypersensitivity to rabeprazole, substituted benzimidazoles or to any component of the formulation.
Clarithromycin is contraindicated in patients with known hypersensitivity to any macrolide antibiotic.
Concomitant administration of clarithromycin with pimozide and cisapride is contraindicated. There have been post-marketing reports of drug interactions when clarithromycin and/or erythromycin are co-administered with pimozide resulting in cardiac arrhythmias (QT prolongation, ventricular tachycardia, ventricular fibrillation, and torsade de pointes) most likely due to inhibition of hepatic metabolism of pimozide by erythromycin and clarithromycin. Fatalities have been reported. (Please refer to full prescribing information for clarithromycin.) Amoxicillin is contraindicated in patients with a known hypersensitivity to any penicillin. (Please refer to full prescribing information for amoxicillin.)
Additional information about Aciphex
Aciphex Indication: For short-term treatment in the healing and symptomatic relief of erosive or ulcerative gastroesophageal reflux disease (GERD).
Mechanism Of Action: Aciphex 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. Aciphex 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.
Drug Interactions: Atazanavir This gastric pH modifier decreases the levels/effects of atazanavir
Dasatinib Possible decreased levels of dasatinib
Digoxin Aciphex increases the effect of digoxin
Enoxacin The agent decreases the absorption of enoxacin
Indinavir Omeprazole decreases the absorption of indinavir
Itraconazole The proton pump inhibitor decreases the absorption of imidazole
Ketoconazole The proton pump inhibitor decreases the absorption of imidazole
Food Interactions: Not Available
Generic Name: Rabeprazole
Synonyms: Irsogladine Maleate; Rebeprazole sodium
Drug Category: Anti-Ulcer Agents; Enzyme Inhibitors
Drug Type: Small Molecule; Approved; Investigational
Other Brand Names containing Rabeprazole: AcipHex; Pariet;
Absorption: Absolute bioavailability is approximately 52%.
Toxicity (Overdose): Not Available
Protein Binding: 96.3% (bound to human plasma proteins)
Half Life: 1-2 hours (in plasma)
Dosage Forms of Aciphex: Tablet, coated Oral
Chemical IUPAC Name: 2-[[4-(3-methoxypropoxy)-3-methylpyridin-2-yl]methylsulfinyl]-1H-benzimidazole
Chemical Formula: C18H21N3O3S
Rabeprazole on Wikipedia: http://en.wikipedia.org/wiki/Rabeprazole
Organisms Affected: Humans and other mammals