Pronunciation: ra-BEP-ra-zole SOE-dee-um
Class: Proton pump inhibitor
- Tablets, delayed-release, oral 20 mg
Suppresses gastric acid secretion by blocking acid (proton) pump within gastric parietal cells.
T max is 2 to 5 h. Oral bioavailability is approximately 52%.
Protein binding is 96.3%.
Extensively metabolized in liver by CYP3A to sulphone metabolite and CYP2C19 to desmethyl rabeprazole. Thioether and sulphone metabolites are formed by reduction of rabeprazole. These metabolites do not have significant antisecretory activity. CYP2C19 exhibits genetic polymorphism caused by deficiency in some subpopulations (white patients, 3% to 5%; Asian patients, 17% to 20%).
Plasma half-life is 1 to 2 h. Eliminated in urine (90% as thioether carboxylic acid, glucuronide, and mercapturic acid); remainder recovered in feces. No unchanged drug recovered.
Special PopulationsRenal Function Impairment
No pharmacokinetic differences in ESRD compared with healthy volunteers.Hepatic Function Impairment
For chronic mild to moderate hepatic impairment, AUC approximately doubled and elimination half-life was 2- to 3-fold higher, total Cl decreased to less than half. For mild to moderate hepatic impairment, C max increased approximately 20% (not significant).Elderly
AUC values doubled; C max increased 60%.Children
Pharmacokinetics in patients 12 to 16 y of age with gastroesophageal reflux disease (GERD) were within the range observed in healthy adults.Gender
Pharmacokinetics did not differ between men and women.Race
Values for AUC for healthy Japanese men were approximately 50% to 60% higher than values for healthy men in the United States.
Indications and Usage
Short-term treatment in healing and symptomatic relief of duodenal ulcers and erosive or ulcerative GERD; maintaining healing and reducing relapse rates of heartburn symptoms in patients with erosive or ulcerative GERD; treatment of daytime and nighttime heartburn and other symptoms associated with GERD; long-term treatment of pathological hypersecretory conditions, including Zollinger-Ellison syndrome; in combination with amoxicillin and clarithromycin to eradicate Helicobacter pylori in patients with H. pylori infection and duodenal ulcer disease.
Prevention of GI bleeding in patients receiving antiplatelets.
Known hypersensitivity to rabeprazole or substituted benzimidazoles, or to any component of the formulation.
Dosage and AdministrationDuodenal Ulcers
PO 20 mg/day after the morning meal for 4 wk; additional therapy may be required for some patients.Short-Term Treatment of GERD
Adults and Children 12 y and older
PO 20 mg once daily for up to 8 wk.Erosive or Ulcerative GERD
PO 20 mg/day for 4 to 8 wk; an additional 8 wk may be considered for patients who do not heal. For the maintenance healing of GERD, 20 mg/day.Pathological Hypersecretory Conditions
PO 60 mg/day. Adjust dose to individual patient needs. Dosages up to 100 mg daily or 60 mg twice daily have been administered.H. Pylori Eradication
PO Rabeprazole 20 mg plus amoxicillin 1,000 mg plus clarithromycin 500 mg twice daily for 7 days with morning and evening meals.
- Tablets should be swallowed whole; do not chew, crush, or split.
- May take with or without food.
Store between 59° and 86°F. Protect from moisture.
Atazanavir plasma concentrations may be reduced, decreasing the efficacy. Coadministration is not recommended.Azole antifungals (eg, itraconazole, ketoconazole)
The bioavailability of certain azole antifungals may be decreased because of a possible reduction in tablet dissolution in the presence of a high gastric pH. If coadministration cannot be avoided, administering the azole antifungal with a cola beverage during coadministration with rabeprazole may minimize changes in the azole antifungal's bioavailability.Calcium salts
Calcium absorption may be reduced, decreasing the therapeutic effect. Larger calcium doses may be needed, especially in patients taking long-term rabeprazole therapy.Clarithromycin
Combined administration of rabeprazole, amoxicillin, and clarithromycin resulted in increased rabeprazole and 14-hydroxyclarithromycin plasma concentrations. These increases are not expected to produce safety concerns.Clopidogrel
The antiplatelet activity of clopidogrel may be decreased. Avoid coadministration unless there is a specific indication for a proton pump inhibitor. H 2 receptor antagonists (eg, ranitidine) may be a safer alternative.Digoxin
Increased serum digoxin concentrations may occur. Because digoxin has a narrow therapeutic index, clinical and laboratory monitoring is warranted, especially if digoxin concentrations are in the upper range when rabeprazole is started.Drugs dependent on gastric pH for absorption (eg, digoxin, ketoconazole)
Rabeprazole produces sustained inhibition of gastric acid secretion. An interaction with compounds that are dependent on gastric pH for absorption may occur because of the magnitude of acid suppression observed with rabeprazole. Plasma levels of digoxin may be increased, while ketoconazole concentrations may be decreased.Erlotinib
Plasma concentration and pharmacologic effects of erlotinib may be decreased. The increase in gastric pH associated with rabeprazole therapy decreases the solubility and bioavailability of erlotinib. Administration of an antacid several hours before or after erlotinib may be considered as an alternative to rabeprazole.Fluvoxamine
Rabeprazole plasma concentrations may be elevated, increasing the pharmacologic effects and risk of adverse reactions. Monitor for rabeprazole adverse reactions.Ginkgo biloba
Rabeprazole plasma concentrations may be reduced, decreasing the therapeutic effect. Caution patients taking rabeprazole to avoid ginkgo biloba.Mycophenolate
Plasma concentration and pharmacologic effects of mycophenolate may be decreased. The mycophenolate dose may need to be increased. Enteric-coated mycophenolate is not expected to be affected by concurrent use with proton pump inhibitors.Rilpivirine
Plasma concentrations and pharmacologic effects of rilpivirine may be reduced, possibly resulting in loss of virologic response or resistance. Coadministration is contraindicated.Salicylates (eg, aspirin)
Proton pump inhibitor–mediated increase in gastric pH results in a more rapid dissolution and release of salicylate from the enteric-coated product, which increases gastric adverse reactions. Patients at risk of serious gastric disorders due to the release of salicylates in the stomach should avoid concurrent use of these agents.Tyrosine kinase receptor inhibitors (eg, dasatinib, nilotinib)
Plasma concentrations and pharmacologic effects of dasatinib and nilotinib may be reduced. The increase in gastric pH associated with rabeprazole therapy decreases the solubility and bioavailability of dasatinib and nilotinib. Coadminister with caution. Separating the administration times is not likely to circumvent the interaction. However, administration of an antacid or histamine H 2 blocker several hours before or after dasatinib or nilotinib may be considered as an alternative to rabeprazole.Voriconazole
Rabeprazole plasma concentrations may be elevated, increasing the pharmacologic effects and risk of adverse reactions. Close clinical monitoring for rabeprazole adverse reactions is warranted. Initial reduction in the rabeprazole dose may be needed when voriconazole is added.Warfarin
Increased INR and PT have been reported with concurrent rabeprazole. Monitor INR and PT.
Headache (10%); dizziness; coma, disorientation/delirium (postmarketing).
Bullous eruptions, severe dermatologic eruptions including erythema multiforme, Stevens-Johnson syndrome, TEN (postmarketing).
Diarrhea, nausea (5%); abdominal pain, vomiting (4%); flatulence (3%); constipation (2%); dry mouth.
Hepatic encephalopathy; hepatitis; increased hepatic enzymes; jaundice (postmarketing).
Agranulocytosis, hemolytic anemia, leukopenia, pancytopenia, thrombocytopenia (postmarketing).
Hyperammonemia, TSH elevations (postmarketing).
Arthralgia; myalgia; bone fractures, rhabdomyolysis (postmarketing).
Pain, pharyngitis (3%); infection (2%); peripheral edema; anaphylaxis, angioedema, interstitial nephritis, interstitial pneumonia, sudden death (postmarketing).
Category B .
Safety and efficacy not established in the short-term treatment of GERD in children younger than 12 y. For other indications, safety and efficacy not established.
Use with caution in patients with severe hepatic impairment.
Use may be associated with an increased risk of osteoporosis-related fractures of the hip, wrist, or spine.
Symptomatic response to rabeprazole does not preclude gastric malignancy.
No experience with large doses.
- Instruct patients to take each dose without regard to meals but to take with food if stomach upset occurs.
- Instruct patients to swallow tablets whole and not to split, crush, or chew the tablets.
- Instruct patients to report any of the following to health care provider: bloody or coffee ground–like vomit; black, tarry stools; recurrent heartburn; recurrent indigestion or abdominal pain; increasing need for antacid use; any bothersome adverse reactions (eg, headache, constipation, gas).
Copyright © 2009 Wolters Kluwer Health.
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