Pronunciation: ra-BEP-ra-zole SOE-dee-um
Class: Proton pump inhibitor

Trade Names

Aciphex
- Tablets, delayed-release, oral 20 mg

Pariet (Canada)

Pharmacology

Suppresses gastric acid secretion by blocking acid (proton) pump within gastric parietal cells.

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Pharmacokinetics

Absorption

T _max is 2 to 5 h. Oral bioavailability is approximately 52%.

Distribution

Protein binding is 96.3%.

Metabolism

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%).

Elimination

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 Populations

Renal 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.

Unlabeled Uses

Prevention of GI bleeding in patients receiving antiplatelets.

Contraindications

Known hypersensitivity to rabeprazole or substituted benzimidazoles, or to any component of the formulation.

Dosage and Administration

Duodenal Ulcers
Adults

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
Adults

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
Adults

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
Adults

PO Rabeprazole 20 mg plus amoxicillin 1,000 mg plus clarithromycin 500 mg twice daily for 7 days with morning and evening meals.

General Advice

• Tablets should be swallowed whole; do not chew, crush, or split.
• May take with or without food.

Storage/Stability

Store between 59° and 86°F. Protect from moisture.

Drug Interactions

Atazanavir

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.

Adverse Reactions

CNS

Headache (10%); dizziness; coma, disorientation/delirium (postmarketing).

Dermatologic

Bullous eruptions, severe dermatologic eruptions including erythema multiforme, Stevens-Johnson syndrome, TEN (postmarketing).

GI

Diarrhea, nausea (5%); abdominal pain, vomiting (4%); flatulence (3%); constipation (2%); dry mouth.

Hepatic

Hepatic encephalopathy; hepatitis; increased hepatic enzymes; jaundice (postmarketing).

Hematologic-Lymphatic

Agranulocytosis, hemolytic anemia, leukopenia, pancytopenia, thrombocytopenia (postmarketing).

Metabolic-Nutritional

Hyperammonemia, TSH elevations (postmarketing).

Musculoskeletal

Arthralgia; myalgia; bone fractures, rhabdomyolysis (postmarketing).

Miscellaneous

Pain, pharyngitis (3%); infection (2%); peripheral edema; anaphylaxis, angioedema, interstitial nephritis, interstitial pneumonia, sudden death (postmarketing).

Precautions

Pregnancy

Category B .

Lactation

Undetermined.

Children

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.

Hepatic Function

Use with caution in patients with severe hepatic impairment.

Bone fracture

Use may be associated with an increased risk of osteoporosis-related fractures of the hip, wrist, or spine.

Gastric malignancy

Symptomatic response to rabeprazole does not preclude gastric malignancy.

Overdosage

Symptoms

No experience with large doses.

Patient Information

• 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.