rabeprazole (Rx)

1-10%

Headache (2-10%)

Constipation (2%)

Diarrhea (2-5%)

Flatulence (3%)

Pain (3%)

Pharyngitis (3%)

Abdominal pain (4%)

<1%

Agitation

Agranulocytosis

Alopecia

Anemia

Angioedema

Chest pain

Delirium

Erythema multiforme

Hypokalemia

Hypomagnesemia

Hyponatremia

Jaundice

Leukocytosis

Leukopenia

Migraine

Osteoporosis related fracture

Rhabdomyolysis

Stevens-Johnson syndrome

Sudden death

Toxic epidermal necrolysis

Abnormal taste

Postmarketing Reports

Cutaneous and systemic lupus erythematosus

Cyanocobalamin (vitamin B-12) deficiency

Blood and lymphatic system disorders: Hemolytic anemia, pancytopenia, thrombocytopenia

Ear and labyrinth disorders: Vertigo

Eye disorders: Blurred vision

Immune system disorders: Anaphylaxis, toxic epidermal necrolysis (some fatal)

Infections and ifestations: Clostridium difficile-associated diarrhea

Investigations: Increases in prothrombin time/INR (in patients treated with concomitant warfarin), TSH elevations

Metabolism and nutrition disorders: Hyperammonemia

Musculoskeletal system disorders: Bone fracture

Nervous system disorders: Coma

Psychiatric disorders: Disorientation

Renal and urinary disorders: Interstitial nephritis

Respiratory, thoracic and mediastinal disorders: Interstitial pneumonia

Skin and subcutaneous tissue disorders: Severe dermatologic reactions including bullous and other drug eruptions of the skin

Gastrointestinal: Fundic gland polyps

Acute tubulointerstitial nephritis

Contraindications

Hypersensitivity to rabeprazole or other proton pump inhibitors (PPIs)

Rilpivirine-containing products

Cautions

PPIs are possibly associated with increased incidence of Clostridium difficile-associated diarrhea (CDAD); consider diagnosis of CDAD for patients taking PPIs with diarrhea that does not improve

In liver disease may require dosage reduction

Cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE) reported with PPIs; avoid using for longer than medically indicated; discontinue if signs or symptoms consistent with CLE or SLE are observed and refer patient to specialist; most patients improve with discontinuation of PPI alone in 4-12 weeks; serological testing (e.g. ANA) may be positive and elevated serological test results may take longer to resolve than clinical manifestations

Use of proton pump inhibitors may increase risk of salmonella and campylobacter infection

Reduce of symptoms does not eliminate presence of gastric malignancy; consider additional follow-up and diagnostic testing in adult patients who have suboptimal response or early symptomatic relapse after completing treatment with a PPI

Published observational studies suggest that PPI therapy may be associated with an increased risk of osteoporosis-related fractures of the hip, wrist, or spine; particularly with prolonged (>1 yr), high-dose therapy

Decreased gastric acidity increases serum chromogranin A (CgA) levels and may cause false positive diagnostic results for neuroendocrine tumors; temporarily discontinue PPIs before assessing CgA levels

Hypomagnesemia may occur with prolonged use (ie, >1 yr); adverse effects, such as tetany, arrhythmias, or seizures, may result; in 25% of cases reviewed, magnesium supplementation alone did not improve low serum magnesium levels, and the PPI had to be discontinued; consider monitoring magnesium levels prior to initiation of PPI treatment and periodically

Monitor for increases in INR and prothombin time when coadministered with warfarin

Daily long-term use (e.g., longer than 3 years) may lead to malabsorption or a deficiency of cyanocobalamin

Acute interstitial nephritis reported in patients taking proton pump inhibitors

Concomitant use of proton pump inhibitors with methotrexate, primarily at high dose, may elevate and prolong serum concentrations of methotrexate and/or its metabolite, possibly leading to methotrexate toxicities; in high-dose methotrexate administration, a temporary withdrawal of the PPI may be considered in some patients

PPI therapy is associated with increased risk of fundic gland polyp; risk increases with long-term use >1 year; patient may be asymptomatic; problem usually identified incidentally on endoscopy; use shortest duration of therapy appropriate to condition being treated

Acute tubulointerstitial nephritis (TIN) reported in patients taking PPIs; may occur at any point during PPI therapy; patients may present with varying signs and symptoms from symptomatic hypersensitivity reactions to non-specific symptoms of decreased renal function (e.g., malaise, nausea, anorexia); in reported case series, some patients were diagnosed on biopsy and in absence of extra-renal manifestations (eg, fever, rash or arthralgia); discontinue therapy and evaluate patients with suspected acute TIN

Pregnancy

There are no available human data in pregnant women to inform drug associated risk; background risk of major birth defects and miscarriage for indicated populations are unknown; however, background risk in U.S. general population of major birth defects is 2-4% and of miscarriage is 15- 20% of clinically recognized pregnancies; no evidence of adverse developmental effects were seen in animal reproduction studies with rabeprazole administered during organogenesis at 13 and 8 times human area under plasma concentration-time curve (AUC) at recommended dose for GERD, in rats and rabbits, respectively; changes in bone morphology were observed in offspring of rats treated with oral doses of different PPI through most of pregnancy and lactation; when maternal administration was confined to gestation only, there were no effects on bone physeal morphology in offspring at any age

Lactation

Lactation studies have not been conducted to assess presence in human milk, effects on breastfed infant, or effects on milk production; drug is present in rat milk; development and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy and any potential adverse effects on breastfed infant from drug or from underlying maternal condition

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Proton pump inhibitor (PPI); binds to H+/K+-exchanging ATPase (proton pump) in gastric parietal cells, blocking acid secretion

Absorption

Bioavailability: 52%

Onset: Within 1 hr

Duration: 24 hr

Peak plasma time: 2-5 hr (tablet); 1-6.5 hr (capsule)

Distribution

Protein bound: 95-98%

Metabolism

Metabolism: Liver; extensively by hepatic P450 enzyme CYP2C19; second pathway through CYP3A4; also by non-enzymatic reduction

Metabolites (presumed inactive): Rabeprazole thioether, sulfone metabolite, desmethyl metabolite, desmethyl thioether, thioether carboxylic acid

CYP2C19 substrate (minor)

Elimination

Half-life elimination: 1-2 hr, depending on dose

Dialyzable: No

Total body clearance: 4-8 mL/min/kg

Excretion: Urine (90%); feces (10%)

Oral Administration

Delayed-release tablet

• Administer with or without meals
• Swallow tablet whole; do not chew or crush

Delayed-release capsule

• Take 30 minutes before a meal
• Contains enteric coated granules (acid labile); do not chew or crush
• Do not swallow capsule whole
• Open capsule and sprinkle entire contents on small amount of soft food (eg, applesauce, fruit- or vegetable-based baby food, or yogurt) or empty contents into a small amount of liquid (eg, infant formula, apple juice, or pediatric electrolyte solution)
• Take entire dose within 15 minutes of preparation
• Food or liquid should be at or below room temperature; do not store mixture for future use

Missed dose

• Administer a missed dose as soon as possible
• If administration time is close to the following dose, skip missed dose and take current dose
• Do not take 2 doses at the same time

Storage

Delayed release tablet and capsule: Store at room temperature at 77°F (25°C); excursions permitted to 59-86°F (15-30°C)