Rabeprazole Sodium

Trade Names:Aciphex- Tablets, delayed-release 20 mg

Pharmacology

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

Pharmacokinetics

Absorption

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

Distribution

Protein binding is 96.3%.

Metabolism

Extensively metabolized in liver by CYP3A to sulfone metabolite and CYP2C19 to desmethyl rabeprazole. Thioether metabolite is 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 t _½ 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

No pharmacokinetic differences were observed in 10 patients with end-stage renal disease compared with 10 healthy volunteers.

For chronic mild to moderate hepatic function impairment, AUC approximately doubled and elimination t _½ was 2 to 3 fold higher, total Cl decreased to less than half. For mild to moderate hepatic function impairment, C _max increased about 20% (not significant).

AUC values doubled, C _max increased 60%.

Pharmacokinetics in patients 12 to 16 yr of age with GERD were within range observed in healthy adults.

Pharmacokinetics did not differ between men and women.

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 gastroesophageal reflux disease (GERD); maintaining healing and reducing relapse rates of heartburn symptoms in adults and children 12 yr of age and older with 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 .

Contraindications

Known hypersensitivity to rabeprazole or substituted benzimidazoles.

Dosage and Administration

PO 20 mg/day after the morning meal for 4 wk; additional therapy may be required for some patients.

PO 20 mg once daily for up to 8 wk.

PO 20 mg/day for 4 to 8 wk; an additional 8 wk may be considered for patients who do not heal.

PO 20 mg/day.

PO 60 mg/day. Doses up to 100 mg daily or 60 mg twice daily have been administered.

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

• Swallow tablets whole; do not chew, crush, or split.
• May take with or with out food.

Storage/Stability

Store tablets at controlled room temperature (59° to 86°F). Protect from moisture.

Drug Interactions

Atazanavir plasma concentrations may be reduced, decreasing the efficacy. Coadministration is not recommended.

Plasma levels of digoxin may be increased, while ketoconazole concentrations may be decreased.

Increased INR and PT have been reported with concurrent rabeprazole.

Laboratory Test Interactions

None well documented.

Adverse Reactions

CNS

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

Dermatologic

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

EENT

Pharyngitis (3%).

GI

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

Genitourinary

Interstitial nephritis (postmarketing).

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; rhabdomyolysis (postmarketing).

Respiratory

Interstitial pneumonia (postmarketing).

Miscellaneous

Pain (3%); infection (2%); peripheral edema; anaphylaxis, angioedema, coma, 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 yr of age. For other indications, safety and efficacy not established.

Hepatic Function

Use with caution in patients with severe hepatic function impairment.

Gastric malignancy

Symptomatic response to rabeprazole does not preclude gastric malignancy.

Overdosage

Symptoms

No experience with large doses.

Patient Information

• Instruct patient to take each dose without regard to meals but to take with food if stomach upset occurs.
• Instruct patient to swallow tablets whole and not to split, crush, or chew the tablets.
• Remind patient that rabeprazole is to be taken every day and not as needed or only when symptoms are present.
• Remind patient that antacids may be taken concurrently with rabeprazole.
• Instruct patient to report any of the following to health care provider: bloody or coffee ground vomit; black, tarry stools; recurrent heartburn; recurrent indigestion or abdominal pain; increasing need for antacid use; or bothersome adverse reactions (eg, headache, constipation, gas).

Copyright © 2009 Wolters Kluwer Health.