RABEPRAZOLE SODIUM
  • RABEPRAZOLE SODIUM

  • (Generic for ACIPHEX)
  • QTY 30 • 20 MG • TABLET DR • Near 77381

RABEPRAZOLE (ra BE pray zole) prevents the production of acid in the stomach. It is used to treat gastroesophageal reflux disease (GERD), certain ulcers, inflammation of the esophagus, and Zollinger-Ellison Syndrome.

RABEPRAZOLE SODIUM Pediatric Monographs
  • General Administration Information
    For storage information, see the specific product information within the How Supplied section.

    Route-Specific Administration

    Oral Administration
    Oral Solid Formulations
    Delayed-release tablets
    -Swallow whole; do not chew, crush, or split.
    -According to the package labeling, may be administered without regard to meals; however, guidelines recommend administration on an empty stomach, 30 to 60 minutes before meals.
    Delayed-release capsules (e.g., Aciphex Sprinkle)
    -Do not swallow whole, crush, or chew.
    -Open capsules (an arrow imprint on the capsule indicates direction for opening the capsule) and sprinkle contents on a spoonful of soft food (e.g. applesauce, fruit or vegetable based baby food, or yogurt) or liquid (e.g., infant formula, apple juice, or pediatric electrolyte solution). Maintain the food or liquid at or below room temperature.
    -Take the whole dose within 15 minutes of being sprinkled; do not store mixture for future use.
    -Administer with this small amount of food or liquid, 30 minutes before a meal.

    Significant elevations in serum gastrin have been reported with rabeprazole similar to other proton pump inhibitors (PPIs); this effect may be dose-related. Elevations in serum gastrin were reported in 5-10.7% of pediatric patients receiving rabeprazole for 5 days-5 weeks (n = 28-268, age 1 month to 11 years). The clinical significance of these elevations in this population is unknown. Carcinoid tumors are a potential sequelae of prolonged hypergastrinemia secondary to the use of PPIs due to inhibited gastric acid secretion. In over 400 adult patients treated with rabeprazole (10-20 mg/day) for up to one year, the incidence of ECL cell hyperplasia increased with time and dose, which is consistent with the pharmacological action of the drug. No patient developed adenomatoid, dysplastic or neoplastic changes or ECL cells in the gastric mucosa. No patient developed the carcinoid tumors observed in rats. The risk of carcinoid tumors during therapy with PPIs is low based on cumulative safety experience; monitoring of serum gastrin levels during PPI therapy is generally not necessary.

    Diarrhea (1.2-11%) was reported in short-term pharmacokinetic, open-label, and controlled clinical trials of rabeprazole in pediatric patients (n = 24-344, age 1 month-16 years). Although transient diarrhea associated with PPI therapy is typically mild and not troublesome, persistent watery diarrhea may require medical attention. In a prospective multi-center study of 186 pediatric patients (aged 4-36 months) that compared infants and children receiving gastric acidity (GA) inhibitors ranitidine or omeprazole to a healthy control, the use of GA-inhibitors was associated with an increased risk of developing acute gastroenteritis. The patients in the study were otherwise healthy infants and children that were receiving omeprazole for gastroesophageal reflux treatment. In a case-controlled study of 136 pediatric patients (68 patients with Clostridium difficile-associated diarrhea and 68 controls negative for Clostridium difficile-associated diarrhea), the use of proton pump inhibitors was significantly higher in the Clostridium difficile positive group compared with the Clostridium difficile negative group (odds ratio (OR) = 4.5; 95% confidence interval (CI) = 1.4-14.4). In February 2012, the FDA notified the public of a possible association between gastric acid suppression drugs, such as proton pump inhibitors (PPIs), and the development of Clostridium difficile-associated diarrhea (CDAD); suppression from histamine H2 receptor blocker administration is also under review. Gastric acid suppression has been proposed as an independent risk factor for the development of CDAD, particularly with PPIs; however, studies have shown conflicting results. The PPIs, including rabeprazole, are recommended for use in combination with certain antibiotics to eradicate Helicobacter pylori. Consider the diagnosis of CDAD and pseudomembranous colitis in patients presenting with watery diarrhea, stomach pain, and elevated temperature that does not improve following gastric acid suppression therapy and/or antibacterial administration. If diarrhea develops during therapy, the drug should be discontinued. Following diagnosis of pseudomembranous colitis, therapeutic measures should be instituted. Products inhibiting peristalsis are contraindicated in this clinical situation. Practitioners should be aware that antibiotic-associated colitis has been observed to occur over two months or more following discontinuation of systemic antibiotic therapy; a careful medical history should be taken. Healthcare professionals and patients are encouraged to report adverse events or side effects related to the use of these products to the FDA's MedWatch Safety Information and Adverse Event Reporting Program. In general, patients should use the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated.

    As with other proton pump inhibitors, adverse reactions reported during rabeprazole studies are typically gastrointestinal (GI) in nature. The most common GI adverse reactions reported in short-term (less than 12 weeks) pharmacokinetic, open-label, and controlled clinical trials of rabeprazole in pediatric patients (n = 24 to 344, ages 1 month to 16 years) include vomiting (3% to 14%), abdominal pain (3.6% to 12%), diarrhea (1.2% to 11%, and nausea (1.8% to 8.3%). Treatment-related GI reactions reported in an open-label study of infants receiving rabeprazole (n = 344, age 1 to 11 months) include constipation (0.6%) and flatulence (0.6%). Pancreatitis, toothache, and volvulus were each reported in 1 patient (3.6%) in a pharmacokinetic study of pediatric patients receiving rabeprazole (n = 28, age 1 to 11 years); with the exception of volvulus, these reactions were mild and not thought to be related to treatment. Xerostomia was reported in less than 2% of adult patients receiving rabeprazole, and dysgeusia was reported in 6% to 10% of adult patients receiving rabeprazole plus amoxicillin and clarithromycin. Gastric polyps/fundic gland polyps have been reported during postmarketing surveillance.

    General adverse reactions reported in short-term (< 12 weeks) pharmacokinetic, open-label, and controlled clinical trials of rabeprazole in pediatric patients (n = 24-344, age 1 month to 16 years) include headache (5-16.7%), fever (7%), fatigue (4.2%), periorbital edema (4.2%), pharyngolaryngeal pain (4.2%), and chills (3.6%). Dizziness (< 2%) was also reported in adult patients receiving rabeprazole in clinical trials. Other adverse reactions identified during the post-approval use of rabeprazole include: sudden death, coma, disorientation, delirium, and TSH elevations. The relationship between these events and rabeprazole is unclear.

    Rash (unspecified) was reported in 0.6% of infants receiving rabeprazole in an open-label study (n = 344, age 1-11 months). During controlled clinical trials in adults, peripheral edema was reported in < 2% of patients receiving rabeprazole. In addition, anaphylactoid reactions, anaphylaxis, and angioedema have been reported during post-marketing experience. Other adverse reactions identified during the post-approval use of rabeprazole include: bullous rash and other drug eruptions, toxic epidermal necrolysis (some fatal), Stevens-Johnson syndrome, and erythema multiforme. The relationship between these events and rabeprazole is unclear.

    During post marketing surveillance of rabeprazole, the following hematological reactions have been reported: agranulocytosis, hemolytic anemia, hyperammonemia, leukopenia, pancytopenia, and thrombocytopenia. Long-term (e.g., generally > 2-3 years) treatment with acid-suppressing agents can lead to malabsorption of vitamin B12 (cyanocobalamin). In a study of healthy volunteers, omeprazole was associated with a significant reduction in cyanocobalamin absorption (vitamin B12 deficiency). In a large case-controlled study, adult patients with and without an incident diagnosis of vitamin B12 deficiency (n = 25,956 and 184,199, respectively) were compared and a correlation between vitamin B12 deficiency and gastric acid-suppression therapy was found. Patients receiving >= 2 years of a proton pump inhibitor (PPI) or a H2-receptor antagonist were associated with having an increased risk for vitamin B12 deficiency. A dose-dependant relationship was evident, as daily doses > 1.5 PPI pills/d were more strongly associated with vitamin B12 deficiency compared to daily doses < 0.75 pills/d. Consider the possibility of cyanocobalamin deficiency and pernicious anemia if clinical symptoms are observed. Neurological manifestations of pernicious anemia can occur in the absence of hematologic changes.

    Respiratory and infectious adverse reactions reported in short-term (< 12 weeks) pharmacokinetic, open-label, and controlled clinical trials of rabeprazole in pediatric patients (n = 24-344, age 1 month to 16 years) include cough (10.7-14%), asthma (3.6-4.2%), pharyngitis (7.1%), upper respiratory infection (3.6-5%), and viral gastritis (3.6%). Interstitial pneumonia has occurred during post-marketing surveillance of rabeprazole. Gastric acid suppression with proton pump inhibitors has been associated with an increased risk of infection in pediatric patients. A prospective, multi-center study in previously healthy infants and young children found an increased risk in community-acquired pneumonia (12% vs. 2%, p < .05) and acute gastroenteritis (47% vs. 20%, p < .05) in patients receiving gastric acid inhibitors (n = 91) compared to controls (n = 95). Another study in critically ill pediatric patients (n = 60) did not find an increased incidence of ventilator-associated pneumonia in patients receiving acid-suppression therapy compared to those not receiving treatment. Until more is known about the relationship between acid-suppression and pneumonia, clinicians are encouraged to carefully select patients before empirically initiating acid-suppressive therapy with H2-blockers or PPIs. A causal relationship between the use of rabeprazole and pneumonia has not been established. Increasing evidence in adults suggests a link between acid-suppression therapy and pneumonia (community- and hospital-acquired). Several mechanisms have been proposed to account for this association. One hypothesis is that gastric pH serves as a barrier against pathogenic colonization of the gastrointestinal tract. An increase in gastric pH allows for bacterial and viral invasion which, in theory, can precipitate respiratory infections. Another proposed mechanism accounts for the role that gastric acid may have on stimulating the cough reflex that allows for the clearing of infectious agents from the respiratory tract. Finally, the fact that acid-suppressive therapy may impair white blood cell function, which in turn may lead to a depressed immune response to an infection, is listed among possible mechanisms.

    Cases of hypomagnesemia have been reported in association with prolonged (3 months to > 1 year) proton pump inhibitor (PPI) use, including rabeprazole. Generally, hypomagnesemia is corrected with magnesium supplementation; however, in cases where hypomagnesemia is observed during PPI administration, discontinuation of the PPI may also be necessary. Low serum magnesium may lead to serious adverse events such as muscle spasm (tetany), seizures, and irregular heartbeat (arrhythmias). In pediatric patients, irregular heartbeat may cause fatigue, upset stomach, dizziness, and lightheadedness. For patients expected to be on PPI therapy for a prolonged period of time, it is prudent for clinicians to obtain serum magnesium concentrations prior to initiating PPI therapy as well as throughout treatment. Patients on concomitant medications such as digoxin or diuretics may also require periodic monitoring of serum magnesium.

    In controlled treatment trials in adults, pain (unspecified) was reported in 3% of patients receiving rabeprazole compared to 1% receiving placebo. Myalgia and arthralgia were reported in < 2% of patients receiving rabeprazole. In addition, rhabdomyolysis and bone fractures were listed among reported adverse reactions identified during post-marketing surveillance. Proton pump inhibitors (PPIs) have been associated with a possible increased risk of bone fractures of the hip, wrist, and spine, particularly in elderly patients. There have been six epidemiological studies that have reported an increased risk of fractures with the use of PPIs; the studies compared claims data of patients treated with PPIs versus individuals who were not using PPIs. Depending on the study, exposure to PPIs ranged between 1-12 years. The emergence of fractures varied among studies; one study reported an increase in fractures with use of PPIs in the previous year and another study found an increase after 5-7 years of PPI use. Increased risk was primarily observed in adult patients, patients taking prescription PPIs for at least one year, and patients who had been taking high doses (doses greater than those recommended with OTC use). Alternatively, in another epidemiological study with similar study design, a relationship between PPI use and fractures was not established; the study population did not have major risk factors for fracture at study entry. It should be noted that randomized clinical trials (RCTs) of PPIs have not found an increased risk of fractures of the hip, wrist, or spine; some limitations of these RCTs were study duration (generally six months) and insufficient information on effects of higher than recommended doses. The risk of fractures is not known in pediatric patients. Until more data are available, when prescribing PPIs, consider whether a lower dose or shorter duration of therapy would adequately treat the patient's condition. In patients with or at risk for osteoporosis, manage their bone status according to current clinical practice, and ensure adequate vitamin D and calcium supplementation.

    In controlled clinical trials, elevated hepatic enzymes, hepatitis, and hepatic encephalopathy were reported in < 2% of adult patients receiving rabeprazole; reported incidence was not greater than placebo. In addition, jaundice has been reported (without regard to causality) in post-marketing experience with rabeprazole.

    Genitourinary adverse reactions reported in a pharmacokinetic study of pediatric patients receiving rabeprazole (n = 24, age 12-16 years) include dysmenorrhea (4.2%), polyuria (4.2%), and proteinuria (4.2%). Acute interstitial nephritis (AIN) has been reported in patients taking proton pump inhibitors (PPIs), including rabeprazole. AIN is generally attributed to an idiopathic hypersensitivity reaction and may occur at any time during PPI therapy. Discontinue rabeprazole therapy if AIN occurs.

    Cutaneous lupus erythematosus (CLE), systemic lupus erythematosus (SLE), and lupus-like symptoms have occurred in patients taking PPIs, including rabeprazole. Both exacerbation and new onset of existing autoimmune disease have be reported, with the majority of PPI-induced lupus erythematosus cases being CLE. Subacute CLE (SCLE) is the most common form of CLE reported in patients treated with PPIs, occurring within weeks to years after continuous drug therapy in patients ranging from infants to the elderly. Histological findings were usually observed without organ involvement. SLE is less commonly reported; PI associated SLE is generally milder than non-drug induced SLE. Onset of SLE typically occurred within days to years after initiating treatment primarily in patients ranging from infants to the elderly. Most patients presented with rash; however, arthralgia and cytopenia were also reported. Do not administer PPIs for longer than medically indicated. If signs or symptoms consistent with CLE or SLE occur, discontinue the drug and refer the patient to the appropriate specialist for evaluation. Most patients improve with discontinuation of the PPI alone in 4 to 12 weeks; serological testing (ANA) may be positive and elevated serological test results may take longer to resolve than clinical manifestations.

    Blurred vision and vertigo have been reported with rabeprazole in postmarketing surveillance.

    Rabeprazole is contraindicated in patients with known hypersensitivity to rabeprazole or other substituted benzimidazoles such as omeprazole or lansoprazole (i.e., known proton pump inhibitors (PPIs) hypersensitivity). There has been evidence of PPI cross-sensitivity in some sensitive individuals in literature reports. Although rare, occasionally such reactions can be serious (i.e., result in anaphylaxis, angioedema, or acute interstitial nephritis).

    Use rabeprazole with caution in patients with severe hepatic disease or impairment; sufficient data are lacking in this subgroup. The elimination half-life of rabeprazole may be significantly prolonged in patients with hepatic disease; however, no dosage adjustment is recommended in patients with mild to moderate hepatic impairment.

    Use rabeprazole with caution in children with low bone density. Observational studies have suggested that proton pump inhibitors (PPIs) may be associated with an increased risk for osteoporosis related fractures of the hip, wrist, or spine. In studies, patients at highest risk of fracture were those who received high-dose (defined as multiple daily doses) and long-term PPI therapy (a year or longer), particularly elderly patients. The true risk in pediatric patients in not clear. Until more data are available, when prescribing PPIs, consider whether a lower dose or shorter duration of therapy would adequately treat the patient's condition. In patients with or at risk for osteoporosis, manage their bone status according to current clinical practice, and ensure adequate vitamin D and calcium supplementation.

    Daily treatment with a gastric acid-suppressing medication over a long period of time (e.g., 3 months to > 1 year) may lead to hypomagnesemia; cases have been reported in patients taking rabeprazole. Generally, hypomagnesemia is corrected with magnesium supplementation; however, in cases where hypomagnesemia is observed during PPI administration, discontinuation of the PPI may also be necessary. Low serum magnesium may lead to serious adverse events such as muscle spasm (tetany), seizures, and irregular heartbeat (arrhythmias). Use PPIs with caution and, if possible, avoid long-term (> 14 days) use in patients with congenital long QT syndrome, as they may be at higher risk for arrhythmias. In pediatric patients, irregular heartbeat may cause fatigue, upset stomach, dizziness, and lightheadedness. For patients expected to be on PPI therapy for a prolonged period of time, it is prudent for clinicians to obtain serum magnesium concentrations prior to initiating PPI therapy as well as throughout treatment. Patients on concomitant medications such as digoxin or diuretics may also require periodic monitoring of serum magnesium.


    Chronic use of gastric acid-suppressing agents should be used cautiously and with monitoring in patients who are prone to vitamin B12 deficiency. Daily treatment with a gastric acid-suppressing medication, such as rabeprazole, over a long period of time (e.g., generally >= 2-3 years) has been associated with malabsorption of cyanocobalamin in adults. Consider the possibility of cyanocobalamin deficiency if clinical symptoms are observed.

    The use of proton pump inhibitors (PPIs), such as rabeprazole, has been associated with increased risk of Clostridium difficile-associated diarrhea (CDAD). Consider a diagnosis of CDAD for patients taking PPIs who develop diarrhea that does not improve. Advise patients to seek immediate care from a healthcare professional if they experience watery stool that does not go away, abdominal pain, and fever while taking PPIs. Patients should use the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated. The use of gastric acid suppressive therapy, such as PPIs, may increase the risk of enteric infection by encouraging the growth of gut microflora and increasing susceptibility to organisms including Salmonella, Campylobacter jejuni, Escherichia coli, Clostridium difficile, Vibrio cholerae, and Listeria. A systematic review examined the relationship between PPI use and susceptibility to enteric infections and found enhanced susceptibility for Salmonella infections (adjusted RR range: 4.2-8.3 in 2 studies), Campylobacter (RR 3.5-11.7 in 4 studies) and C. difficile infections (RR 1.2-5.0 in 17 out of 27 studies). The PPIs, including rabeprazole, are recommended for use in combination with certain antibiotics to eradicate Helicobacter pylori. Pseudomembranous colitis has been reported with nearly all antibacterial agents and may range in severity from mild to life-threatening. Therefore, it is important to consider this diagnosis in patients who present with diarrhea subsequent to the administration of antibacterial agents in combination with PPIs.

    Gastric polyps/fundic gland polyps have been reported during postmarketing surveillance. Patients are usually asymptomatic and fundic gland polyps are identified incidentally on endoscopy. The risk of fundic gland polyps increases with long term proton pump inhibitor (PPI) use, especially beyond one year. Use the shortest duration of PPI therapy appropriate to treat specific condition. Although gastric cancer is rare in pediatric patients, clinicians should be aware that symptomatic response to therapy with rabeprazole does not preclude the presence of malignancy.

    Use with caution in patients with a history of systemic lupus erythematosus (SLE) as rabeprazole has been reported to activate or exacerbate SLE.

    Administration of rabeprazole may result in laboratory test interference, specifically serum chromogranin A (CgA) tests for neuroendocrine tumors, urine tests for tetrahydrocannabinol (THC), secretin stimulation tests, and diagnostic tests for Helicobacter pylori. Gastric acid suppression may increase serum CgA. Increased CgA concentrations may cause false positive results in diagnostic investigations for neuroendocrine tumors. To prevent this interference, temporarily stop rabeprazole at least 14 days before assessing CgA concentrations and consider repeating the test if initial concentrations are high. If serial tests are performed, ensure the same commercial laboratory is used as reference ranges may vary. Reports have suggested use of proton pump inhibitors (PPIs) may cause false positive urine screening tests for THC. If a PPI-induced false positive urine screen is suspected, confirm the positive results using an alternative testing method. Rabeprazole may cause a hyper-response in gastrin secretion to the secretin stimulation test, falsely suggesting gastrinoma. Health care providers are advised to temporarily stop rabeprazole at least 14 days prior to performing a secretin stimulation test to allow gastrin concentrations to return to baseline. Preparations that combine PPIs with antimicrobials and bismuth are known to suppress H. pylori; thus, ingestion of these preparations within 4 weeks of performing diagnostic tests for H. pylori may lead to false negative results. At a minimum, instruct the patient to avoid the use of rabeprazole in the 1 to 2 weeks prior to the test and the use of antimicrobials and bismuth preparations in the 4 weeks prior to the test.

    Description: Rabeprazole is a gastric proton-pump inhibitor (PPI) indicated for the treatment of gastroesophageal reflux disease (GERD). Although many studies have demonstrated some level of benefit to the use of PPIs in the treatment of GERD or erosive esophagitis when compared to placebo, conflicting evidence on the safety and efficacy of PPIs warrants cautious use of these drugs in pediatric patients, particularly infants. PPIs are not recommended as first-line therapy for symptomatic GERD in otherwise healthy infants (1 to 11 months); nonpharmacologic measures such as diet modification and positioning strategies are recommended first-line and treatment with PPIs should be reserved for use in infants with acid reflux disease diagnosed by endoscopy (e.g., erosive esophagitis). Rabeprazole is more effective than ranitidine in the treatment of GERD. On the basis of available research, no clear advantage has been demonstrated for the use of one PPI over another in the treatment of GERD. Instead, a key to optimizing effectiveness is tailoring dosage timing; administer traditional delayed release PPIs 30 to 60 minutes before a meal for maximal pH control. A one-time switch to a different PPI in a refractory patient may be useful. Rabeprazole is also used off-label in pediatric patients in combination with antibiotics in the eradication of Helicobacter pylori (H. pylori) infection to reduce the risk of duodenal ulcer recurrence. PPIs have been associated with an increased risk of Clostridium difficile-associated diarrhea. In a retrospective, case-controlled trial in 136 pediatric patients, the use of a PPI was significantly higher in the Clostridium difficile positive group compared with the Clostridium difficile negative group (OR = 4.5; 95% CI = 1.4 to 14.4). Rabeprazole delayed-release sprinkle-capsules are FDA-approved in pediatric patients as young as 1 year; delayed-release tablets are FDA-approved in pediatric patients as young as 12 years.

    For the short-term treatment of gastroesophageal reflux disease (GERD):
    Oral dosage (delayed-release sprinkle capsules):
    Children 1 to 11 years weighing less than 15 kg: 5 mg PO once daily given 30 minutes before a meal for 12 weeks, with the option to increase to 10 mg/day if inadequate response.
    Children 1 to 11 years weighing 15 kg or more: 10 mg PO once daily given 30 minutes before a meal for 12 weeks. A maximum dose of 20 mg PO once daily was used in patients weighing 15 kg or more in a randomized, double-blind study (n = 127, age 1 to 11 years); however the rate of endoscopic/histologic healing was similar in patients receiving the 20 mg dose compared to those receiving the 10 mg dose (78% vs. 76%) and the rate of adverse reactions (vomiting and abdominal pain) thought to be related to rabeprazole was higher in those receiving 20 mg.
    Oral dosage (delayed-release tablets):
    Children and Adolescents 12 to 17 years: 20 mg PO once daily given 30 to 60 minutes before the morning meal for 8 weeks.

    For Helicobacter pylori (H. pylori) eradication*:
    -in combination with amoxicillin and clarithromycin:
    Oral dosage:
    Children and Adolescents: 1.5 to 2.5 mg/kg/day PO divided twice daily (Max: 20 mg/dose) in combination with amoxicillin and clarithromycin for 14 days. Triple therapy with standard-dose amoxicillin, clarithromycin, and a proton pump inhibitor is a first-line treatment option for patients infected with fully susceptible H. pylori strains or strains susceptible to clarithromycin but resistant to metronidazole. In cases of penicillin allergy, use metronidazole in place of amoxicillin for patients infected with fully susceptible strains.
    -in combination with amoxicillin and metronidazole:
    Oral dosage:
    Children and Adolescents: 1.5 to 2.5 mg/kg/day PO divided twice daily (Max: 20 mg/dose) in combination with amoxicillin and metronidazole for 14 days. Triple therapy with standard-dose amoxicillin, metronidazole, and a proton pump inhibitor (PPI) is a first-line treatment option for patients infected with H. pylori strains with known susceptibility to metronidazole and resistance to clarithromycin. Triple therapy with high-dose amoxicillin, metronidazole, and a PPI is a first-line treatment option for patients infected with H. pylori strains with dual resistance to clarithromycin and metronidazole or strains with unknown susceptibility.
    -as part of a sequential therapy regimen:
    Oral dosage:
    Children and Adolescents: 1.5 to 2.5 mg/kg/day PO divided twice daily (Max: 20 mg/dose) for 10 days. Use in combination with amoxicillin for days 1 through 5, and then clarithromycin and metronidazole for days 6 through 10. Sequential therapy is a first-line treatment option for patients infected with fully susceptible H. pylori strains. Sequential therapy is not recommended if susceptibility testing is unavailable.
    -as part of a quadruple therapy regimen:
    Oral dosage:
    Children and Adolescents: 1.5 to 2.5 mg/kg/day PO divided twice daily (Max: 20 mg/dose) in combination with amoxicillin, metronidazole, and clarithromycin for 14 days. Concomitant quadruple therapy with amoxicillin, metronidazole, clarithromycin, and a proton pump inhibitor is a first-line treatment option for patients infected with H. pylori strains with dual resistance to clarithromycin and metronidazole or strains with unknown susceptibility.

    Maximum Dosage Limits:
    -Neonates
    Safety and efficacy have not been established.
    -Infants
    Safety and efficacy have not been established.
    -Children
    1 to 11 years: 10 mg/day PO (delayed-release capsules) is the FDA-approved maximum; however, up to 2.5 mg/kg/day PO (Max: 40 mg/day) has been used off-label for H. pylori eradication.
    12 years: 20 mg/day PO is the FDA-approved maximum; however, up to 40 mg/day PO has been used off-label for H. pylori eradication.
    -Adolescents
    20 mg/day PO is the FDA-approved maximum; however, up to 40 mg/day PO has been used off-label for H. pylori eradication.

    Patients with Hepatic Impairment Dosing
    Use rabeprazole with caution in patients with severe hepatic impairment; specific dosage recommendations are not available. No dosage adjustment is recommended in patients with mild to moderate hepatic impairment.

    Patients with Renal Impairment Dosing
    Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

    *non-FDA-approved indication

    Monograph content under development

    Mechanism of Action: Rabeprazole is a substituted benzimidazole proton-pump inhibitor (PPI) that suppresses gastric acid secretion. It inhibits the gastric (H+, K+)-ATPase enzyme pump at the secretory surface of the gastric parietal cell. This action is partially reversible; rabeprazole dissociates from the enzyme more readily than omeprazole. Rabeprazole is 2 to 10-fold more potent in vitro than omeprazole. In gastric parietal cells, rabeprazole is protonated, accumulates, and is transformed to an active sulfonamide. A significant increase in gastric pH and decrease in basal acid output follow oral administration of rabeprazole. The median inhibitory effect of rabeprazole on 24 hour gastric acidity is 88% of maximal after the first dose. Rabeprazole 20 mg inhibits basal and peptone meal-stimulated acid secretion versus placebo by 86% and 95%, respectively, and increases the percent of a 24 hour period that the gastric pH exceeds 3.0 from 10% to 65%. Rabeprazole does not antagonize H2 or cholinergic receptors.

    Significant in vitro activity against Helicobacter pylori (H. Pylori) has been demonstrated. The minimum inhibitory concentrations (MICs) for rabeprazole are lower than those of omeprazole and lansoprazole. The clinical significance of this finding has not been established. Rabeprazole monotherapy increases the clearance rate of H. pylori; however, eradication does not occur without antimicrobial therapy.

    Pharmacokinetics: Rabeprazole is administered orally. Rabeprazole is 96.3% bound to human plasma proteins. A significant proportion of rabeprazole is metabolized by systemic nonenzymatic reduction to a thioether compound. Metabolism of rabeprazole also occurs in the liver via hepatic CYP3A4 (sulphone metabolite) and CYP2C19 (desmethyl rabeprazole). The thioether and sulphone are the primary metabolites measured in human plasma. These metabolites were not observed to have significant antisecretory activity. The plasma elimination half-life of rabeprazole ranges from 1 to 2 hours. After a single oral dose of 14C-labeled rabeprazole, about 90% of the drug was eliminated in the urine, primarily as thioether carboxylic acid, its glucuronide, and mercapturic acid metabolites. The remainder of the dose was recovered in the feces as metabolites. No unchanged rabeprazole was recovered in the urine or feces.

    Affected cytochrome P450 isoenzymes: CYP2C19
    Rabeprazole is extensively metabolized. A significant portion of rabeprazole is metabolized via systemic nonenzymatic reduction to a thioether compound. Rabeprazole is also metabolized to sulphone and desmethyl compounds via cytochrome P450 in the liver. In vitro studies have demonstrated that primarily metabolism by CYP3A4 results in the sulphone metabolite, and further metabolism by CYP2C19 results in desmethyl rabeprazole. The thioether metabolite is formed by reduction of rabeprazole. Rabeprazole was studied in a clinical trial in Japanese adult patients categorized as either poor or extensive metabolizers of the CYP2C19 genotype; gastric acid suppression was higher in poor metabolizers as compared to extensive metabolizers. In theory, this could be due to higher rabeprazole plasma concentrations in CYP2C19 poor metabolizers. It is unknown whether interactions of rabeprazole with other drugs metabolized by CYP2C19 would be different between extensive metabolizers and poor metabolizers. Although rabeprazole is metabolized to some extent by CYP3A4, significant CYP3A-mediated drug interactions are generally not likely because rabeprazole has a low affinity for a range of CYP isoenzymes.


    -Route-Specific Pharmacokinetics
    Oral Route
    Delayed-release tablets
    Rabeprazole delayed-release tablets are enteric-coated to allow rabeprazole sodium, which is acid labile, to pass through the stomach relatively intact. The absolute bioavailability of rabeprazole is about 52%. Peak plasma concentrations occur over a range of 2 to 5 hours. Food delays the absorption, but does not affect the peak concentrations or bioavailability.

    Delayed-release capsules
    After oral administration (the delayed-release capsules opened and granules sprinkled on 15 mL of applesauce under fasting conditions), peak plasma concentrations of rabeprazole occur over 1 to 6.5 hours, with a median of 2.5 hours. The Cmax and AUC were decreased by 55% and 33%, respectively, after oral administration (the delayed-release capsules opened and granules sprinkled on 15 mL of applesauce) and given with a high-fat meal in healthy adults.


    -Special Populations
    Pediatrics
    Neonates and Infants
    After the administration of rabeprazole granules from delayed-release capsules, the median clearance of rabeprazole was 1.05 L/hour (0.0543 to 3.44 L/hour) in neonates and 4.46 L/hour (0.822 to 12.4 L/hour) in infants 1 to 11 months.

    Children 1 to 11 years
    In a pharmacokinetic study (n = 28, ages 1 to 11 years), exposure to rabeprazole after doses of 0.5 mg/kg and 1 mg/kg was consistent with that seen in adults after doses of 10 and 20 mg. Although the mean clearance was similar in children (30.8 to 42.8 L/hour) to that reported in adolescents (38.3 to 51.5 L/hour) and adults (33 to 49 L/hour), the mean clearance when corrected for body weight was higher in children (25.8 to 30.8 mL/minute/kg) compared to adolescents (10.1 to 12.6 mL/minute/kg) and adults (4.37 to 10.1 mL/minute/kg), indicating that approximately 2 to 3 times the mg/kg dose is needed in children to achieve comparable rabeprazole concentrations to those seen in adults. The mean Tmax and half-life after doses of 0.14 to 1 mg/kg were 1.52 to 2.43 hours and 1.1 to 1.9 hours, respectively.

    Children and Adolescents 12 to 16 years
    The pharmacokinetics of rabeprazole in older children and adolescents are similar to those seen in adults. The mean Tmax, half-life, and clearance was 3.4 to 4.1 hours, 0.58 to 0.97 hours, and 10.1 to 12.6 mL/minute/kg, respectively, in patients receiving doses of 10 to 20 mg (n = 24, age 12 to 16 years). In contrast to adults, in whom accumulation after multiple doses of rabeprazole has not been reported, an increase in exposure of approximately 40% was noted after multiple daily doses of 20 mg compared to exposure after a single dose in adolescents.

    Hepatic Impairment
    Rabeprazole serum concentrations are increased in patients with liver disease. In a single dose study of 10 adult patients with chronic mild to moderate cirrhosis, the AUC was approximately doubled, the elimination half-life was 2- to 3- fold higher, and total body clearance of rabeprazole was decreased to less than half compared to values in healthy men. In another study of mild to moderate hepatic impairment (multiple-dose study; 12 patients), the AUC and Cmax values increased approximately 20% compared to values in healthy age- and gender-matched subjects; however, these increases were not statistically significant. No information exists on rabeprazole disposition in patients with severe hepatic impairment.

    Renal Impairment
    Rabeprazole serum concentrations are not affected by renal dysfunction or hemodialysis. In patients with stable end-stage renal disease requiring maintenance hemodialysis, no clinically significant differences in rabeprazole pharmacokinetics were observed compared to healthy volunteers.

    Ethnic Differences
    CYP2C19 displays a known genetic polymorphism due to its deficiency in some sub-populations (e.g., 3% to 5% of Caucasians and African-Americans and 17% to 20% of Asians are poor metabolizers); these patients experience slower metabolism of rabeprazole. The AUC of rabeprazole was found to be approximately 50% to 60% higher in healthy Japanese men compared to pooled data from healthy men in the United States.

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