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RABEprazole

Pronunciation

(ra BEP ra zole)

Index Terms

  • Pariprazole
  • Rabeprazole Sodium

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule Sprinkle, Oral, as sodium:

AcipHex Sprinkle: 5 mg [contains fd&c blue #2 aluminum lake]

AcipHex Sprinkle: 10 mg [contains fd&c yellow #6 (sunset yellow)]

Tablet Delayed Release, Oral, as sodium:

Aciphex: 20 mg

Generic: 20 mg

Brand Names: U.S.

  • Aciphex
  • AcipHex Sprinkle

Pharmacologic Category

  • Proton Pump Inhibitor
  • Substituted Benzimidazole

Pharmacology

Potent proton pump inhibitor; suppresses gastric acid secretion by inhibiting the parietal cell H+/K+ ATP pump

Absorption

Oral: Well absorbed within 1 hour; food delayed absorption up to 4 hours or longer

Metabolism

Hepatic via CYP3A and 2C19 to inactive metabolites; CYP2C19 exhibits a known genetic polymorphism due to its deficiency in some subpopulations (3% to 5% of Caucasians and 17% to 20% of Asians) which results in slower metabolism

Excretion

Urine (90% primarily as thioether carboxylic acid metabolites); remainder in feces

Onset of Action

Within 1 hour

Time to Peak

Plasma:

Adolescents: Tablet: 3.3 to 4.1 hours (James 2007)

Adults: Tablet: 2 to 5 hours; Capsule: 1 to 6.5 hours

Duration of Action

24 hours

Half-Life Elimination

Dose dependent:

Adolescents: ~0.55 to 1 hour (James 2007)

Adults: 1 to 2 hours; two- to threefold higher in patients with mild-to-moderate hepatic impairment

Protein Binding

96.3%

Special Populations: Hepatic Function Impairment

In mild-to-moderate hepatic impairment, AUC approximately doubled, total clearance decreased to less than half, and Cmax increased ~20% (not significant).

Special Populations: Elderly

AUC values approximately doubled; Cmax increased 60%

Special Populations: Race

AUCs for Japanese men were 50% to 60% higher

Use: Labeled Indications

Duodenal ulcers (tablets only): Short-term (4 weeks or fewer) treatment in the healing and symptomatic relief of duodenal ulcers in adults.

Gastroesophageal reflux disease:

Erosive or ulcerative (tablets only): Short-term (4 to 8 weeks) treatment in the healing and symptomatic relief of erosive or ulcerative gastroesophageal reflux disease (GERD) in adults; for maintaining healing and reduction in relapse rates of heartburn symptoms in adults with erosive or ulcerative GERD.

Symptomatic: Treatment of symptomatic GERD for up to 4 weeks in adults (tablets only), up to 8 weeks in children ≥12 years and adolescents (tablets only), and up to 12 weeks in children 1 to 11 years of age (capsules only).

Helicobacter pylori eradication (tablets only): In combination with amoxicillin and clarithromycin as a 3-drug regimen for the treatment of adults with H. pylori infection and duodenal ulcer disease (active or history of within the past 5 years) to eradicate H. pylori.

Pathological hypersecretory conditions (tablets only): Long-term treatment of pathological hypersecretory conditions, including Zollinger-Ellison syndrome in adults.

Canadian labeling: Additional uses (not in US labeling): Treatment of nonerosive reflux disease (NERD); treatment of gastric ulcers

Off Label Uses

Stress ulcer prophylaxis in critically-ill patients

Based on the Surviving Sepsis Campaign International Guidelines for the Management of Severe Sepsis and Septic Shock, stress ulcer prophylaxis using a proton pump inhibitor or a histamine H2-receptor antagonist is recommended in sepsis or septic shock patients who have GI bleeding risk factors.

Additional Off-Label Uses

Duodenal ulcer (maintenance of healing/prevention of relapse); NSAID-induced ulcer (treatment/prevention)

Contraindications

Hypersensitivity (eg, anaphylaxis, anaphylactic shock, angioedema, bronchospasm, acute interstitial nephritis, urticaria) to rabeprazole, other substituted benzimidazoles, or any component of the formulation; concomitant use with rilpivirine-containing products

Dosing: Adult

Duodenal ulcer: Tablets: Oral: 20 mg once daily for ≤4 weeks; additional therapy to achieve healing may be required for some patients.

Gastric ulcers: Canadian labeling: Tablets: Oral: 20 mg once daily up to 6 weeks; additional therapy to achieve healing may be required for some patients.

Gastroesophageal reflux disease (GERD): Tablets: Oral:

Erosive or ulcerative GERD: Treatment: 20 mg once daily for 4 to 8 weeks; if inadequate response, may repeat up to an additional 8 weeks; maintenance: 20 mg once daily

Symptomatic GERD: Treatment: 20 mg once daily for ≤4 weeks; if inadequate response, may repeat for an additional 4 weeks.

Helicobacter pylori eradication: Tablets: Oral:

Manufacturer labeling: 20 mg twice daily administered with amoxicillin 1,000 mg and clarithromycin 500 mg twice daily for 7 days

American College of Gastroenterology guidelines (ACG [Chey 2007; Chey 2017]):

Clarithromycin triple regimen: 20 to 40 mg twice daily in combination with clarithromycin 500 mg twice daily and either amoxicillin 1 g twice daily or metronidazole 500 mg 3 times per day; continue regimen for 14 days. Note: Avoid use of clarithromycin triple therapy in patients with risk factors for macrolide resistance (eg, prior macrolide exposure, local clarithromycin resistance rates ≥15%, eradication rates with clarithromycin-based regimens ≤85%) (ACG [Chey 2017]; Fallone 2016).

Bismuth quadruple regimen: 20 mg twice daily in combination with tetracycline 500 mg 4 times per day, metronidazole 250 mg 4 times per day or 500 mg 3 or 4 times per day, and either bismuth subcitrate 120 to 300 mg 4 times per day or bismuth subsalicylate 300 mg 4 times per day; continue regimen for 10 to 14 days.

Concomitant regimen: 20 mg twice daily in combination with amoxicillin 1 g twice daily, clarithromycin 500 mg twice daily, and either metronidazole or tinidazole 500 mg twice daily; continue regimen for 10 to 14 days.

Sequential regimen: 20 mg twice daily plus amoxicillin 1 g twice daily for 5 to 7 days; then continue rabeprazole along with clarithromycin 500 mg twice daily, and either metronidazole or tinidazole 500 mg twice daily for 5 to 7 days.

Hybrid regimen: 20 mg twice daily plus amoxicillin 1 g twice daily for 7 days; then continue rabeprazole and amoxicillin along with clarithromycin 500 mg twice daily, and either metronidazole or tinidazole 500 mg twice daily for 7 days.

Levofloxacin triple regimen: 20 mg twice daily in combination with amoxicillin 1 g twice daily and levofloxacin 500 mg once daily; continue regimen for 10 to 14 days.

Levofloxacin sequential regimen: 20 to 40 mg twice daily plus amoxicillin 1 g twice daily for 5 to 7 days; then continue rabeprazole along with levofloxacin 500 mg once daily, and either metronidazole or tinidazole 500 mg twice daily for 5 to 7 days.

LOAD regimen: 40 mg once daily in combination with levofloxacin 250 mg once daily, doxycycline 100 mg once daily, and nitazoxanide 500 mg twice daily; continue regimen for 7 to 10 days.

Hypersecretory conditions (including Zollinger-Ellison Syndrome): Tablets: Oral: Initial: 60 mg once daily; adjust dose to patient needs (some may require divided doses). Doses as high as 100 mg once daily and 60 mg twice daily have been used; continue as long as clinically indicated.

Nonerosive reflux disease (NERD): Canadian labeling: Tablets: Oral: Treatment: 10 mg (maximum: 20 mg once daily) for 4 weeks; lack of symptom control after 4 weeks warrants further evaluation

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Gastroesophageal reflux disease (GERD), symptomatic:

Children 1 to 11 years: Capsules: Oral:

<15 kg: 5 mg once daily for ≤12 weeks; if inadequate response may increase to 10 mg once daily.

≥15 kg: 10 mg once daily for ≤12 weeks.

Children ≥12 years and Adolescents: Oral: Tablets: 20 mg once daily for ≤8 weeks.

Dosing: Renal Impairment

No dosage adjustment necessary.

Dosing: Hepatic Impairment

Mild-to-moderate impairment (Child-Pugh class A or B): No dosage adjustment necessary.

Severe impairment (Child-Pugh class C): Avoid use; if treatment is necessary, monitor for adverse reactions.

Administration

May be administered with an antacid.

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

Tablets: Swallow whole; do not crush, split, or chew; may administer with or without food. However, when used for the treatment of duodenal ulcers, administer after a meal; when used for the eradication of H. pylori, administer with the morning and evening meals.

Dietary Considerations

Capsules: Take 30 minutes before a meal.

Tablets: When used for the treatment of duodenal ulcers, administer after a meal; when used for the eradication of Helicobacter pylori, administer with the morning and evening meals.

Storage

Store at 25°C (77°F); excursions are permitted between 15°C and 30°C (59°F and 86°F). Protect from moisture.

Drug Interactions

Acalabrutinib: Proton Pump Inhibitors may decrease the serum concentration of Acalabrutinib. Avoid combination

Amodiaquine: CYP2C8 Inhibitors may increase the serum concentration of Amodiaquine. Avoid combination

Amphetamine: Proton Pump Inhibitors may increase the absorption of Amphetamine. Monitor therapy

Atazanavir: Proton Pump Inhibitors may decrease the serum concentration of Atazanavir. Management: See full drug interaction monograph for details. Consider therapy modification

Bisphosphonate Derivatives: Proton Pump Inhibitors may diminish the therapeutic effect of Bisphosphonate Derivatives. Monitor therapy

Bosentan: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Bosutinib: Proton Pump Inhibitors may decrease the serum concentration of Bosutinib. Management: Consider alternatives to proton pump inhibitors, such as antacids or H2 receptor antagonists. Administer alternative agents more than 2 hours before or after bosutinib. Consider therapy modification

Capecitabine: Proton Pump Inhibitors may diminish the therapeutic effect of Capecitabine. Monitor therapy

Cefditoren: Proton Pump Inhibitors may decrease the serum concentration of Cefditoren. Management: If possible, avoid use of cefditoren with proton pump inhibitors (PPIs). Consider alternative methods to minimize/control acid reflux (eg, diet modification) or alternative antimicrobial therapy if use of PPIs can not be avoided. Consider therapy modification

Cefpodoxime: Proton Pump Inhibitors may decrease the serum concentration of Cefpodoxime. Monitor therapy

Cefuroxime: Proton Pump Inhibitors may decrease the absorption of Cefuroxime. Avoid combination

Clopidogrel: RABEprazole may decrease serum concentrations of the active metabolite(s) of Clopidogrel. Management: Due to the possible risk for impaired clopidogrel effectiveness, clinicians should carefully consider the need for proton pump inhibitor therapy in patients receiving clopidogrel. Other acid-lowering therapies do not appear to share this interaction. Consider therapy modification

CYP2C19 Inducers (Strong): May increase the metabolism of CYP2C19 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification

CYP2C8 Substrates (High risk with Inhibitors): CYP2C8 Inhibitors (Moderate) may decrease the metabolism of CYP2C8 Substrates (High risk with Inhibitors). Monitor therapy

CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification

Cysteamine (Systemic): Proton Pump Inhibitors may diminish the therapeutic effect of Cysteamine (Systemic). Monitor therapy

Dabigatran Etexilate: Proton Pump Inhibitors may decrease serum concentrations of the active metabolite(s) of Dabigatran Etexilate. Monitor therapy

Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification

Dabrafenib: May decrease the serum concentration of CYP2C19 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP2C19 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification

Dabrafenib: Proton Pump Inhibitors may decrease the serum concentration of Dabrafenib. Dabrafenib may decrease the serum concentration of Proton Pump Inhibitors. Management: Seek alternatives to the proton pump inhibitor when possible. If concomitant therapy cannot be avoided, monitor for diminished effects of both drugs. Consider therapy modification

Dasatinib: Proton Pump Inhibitors may decrease the serum concentration of Dasatinib. Management: Antacids (taken 2 hours before or after dasatinib administration) can be used in place of the proton pump inhibitor if some acid-reducing therapy is needed. Avoid combination

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Delavirdine: Proton Pump Inhibitors may decrease the serum concentration of Delavirdine. Management: Chronic therapy with proton pump inhibitors (PPIs) should be avoided in patients treated with delavirdine. The clinical significance of short-term PPI therapy with delavirdine is uncertain, but such therapy should be undertaken with caution. Avoid combination

Dexmethylphenidate: Proton Pump Inhibitors may increase the absorption of Dexmethylphenidate. Specifically, proton pump inhibitors may interfere with the normal release of drug from the extended-release capsules (Focalin XR brand), which could result in both increased absorption (early) and decreased delayed absorption. Monitor therapy

Dextroamphetamine: Proton Pump Inhibitors may increase the absorption of Dextroamphetamine. Specifically, the dextroamphetamine absorption rate from mixed amphetamine salt extended release (XR) capsules may be increased in the first hours after dosing. Monitor therapy

Enzalutamide: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring. Consider therapy modification

Enzalutamide: May decrease the serum concentration of CYP2C19 Substrates (High risk with Inducers). Conversely, concentrations of active metabolites may be increased for those drugs activated by CYP2C19. Management: Concurrent use of enzalutamide with CYP2C19 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP2C19 substrate should be performed with caution and close monitoring. Consider therapy modification

Erlotinib: Proton Pump Inhibitors may decrease the serum concentration of Erlotinib. Avoid combination

Fluconazole: May increase the serum concentration of Proton Pump Inhibitors. Monitor therapy

Gefitinib: Proton Pump Inhibitors may decrease the serum concentration of Gefitinib. Management: Avoid use of proton pump inhibitors (PPIs) with gefitinib when possible. If required, administer gefitinib 12 hours after administration of the PPI or 12 hours before the next dose of the PPI. Consider therapy modification

Indinavir: Proton Pump Inhibitors may decrease the serum concentration of Indinavir. Monitor therapy

Iron Salts: Proton Pump Inhibitors may decrease the absorption of Iron Salts. Exceptions: Ferric Carboxymaltose; Ferric Citrate; Ferric Gluconate; Ferric Hydroxide Polymaltose Complex; Ferric Pyrophosphate Citrate; Ferumoxytol; Iron Dextran Complex; Iron Isomaltoside; Iron Sucrose. Monitor therapy

Itraconazole: Proton Pump Inhibitors may decrease the serum concentration of Itraconazole. Consider therapy modification

Ketoconazole (Systemic): Proton Pump Inhibitors may decrease the serum concentration of Ketoconazole (Systemic). Ketoconazole (Systemic) may increase the serum concentration of Proton Pump Inhibitors. Consider therapy modification

Ledipasvir: Proton Pump Inhibitors may decrease the serum concentration of Ledipasvir. Management: PPI doses equivalent to omeprazole 20 mg or lower may be given with ledipasvir under fasted conditions. Administration with higher doses of PPIs, 2 hours after a PPI, or in combination with food and PPIs may reduce ledipasvir bioavailability. Consider therapy modification

Mesalamine: Proton Pump Inhibitors may diminish the therapeutic effect of Mesalamine. Proton pump inhibitor-mediated increases in gastrointestinal pH may cause the premature release of mesalamine from specific sustained-release mesalamine products. Management: Consider avoiding concurrent administration of high-dose proton pump inhibitors (PPIs) with sustained-release mesalamine products. Consider therapy modification

Methotrexate: Proton Pump Inhibitors may increase the serum concentration of Methotrexate. Monitor therapy

Methylphenidate: Proton Pump Inhibitors may increase the absorption of Methylphenidate. Specifically, proton pump inhibitors may interfere with the normal release of drug from the extended-release capsules (Ritalin LA brand), which could result in both increased absorption (early) and decreased delayed absorption. Monitor therapy

Mitotane: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane. Consider therapy modification

Multivitamins/Minerals (with ADEK, Folate, Iron): Proton Pump Inhibitors may decrease the serum concentration of Multivitamins/Minerals (with ADEK, Folate, Iron). Specifically, the absorption of iron may be decreased. Monitor therapy

Mycophenolate: Proton Pump Inhibitors may decrease the serum concentration of Mycophenolate. Specifically, concentrations of the active mycophenolic acid may be reduced. Monitor therapy

Nelfinavir: Proton Pump Inhibitors may decrease serum concentrations of the active metabolite(s) of Nelfinavir. Proton Pump Inhibitors may decrease the serum concentration of Nelfinavir. Avoid combination

Neratinib: Proton Pump Inhibitors may decrease the serum concentration of Neratinib. Specifically, proton pump inhibitors may reduce neratinib absorption. Avoid combination

Nilotinib: Proton Pump Inhibitors may decrease the serum concentration of Nilotinib. Management: Avoid this combination when possible since separation of doses is not likely to be an adequate method of minimizing the interaction. Consider therapy modification

PAZOPanib: Proton Pump Inhibitors may decrease the serum concentration of PAZOPanib. Avoid combination

Pitolisant: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Combined use of pitolisant with a CYP3A4 substrate that has a narrow therapeutic index should be avoided. Other CYP3A4 substrates should be monitored more closely when used with pitolisant. Consider therapy modification

Posaconazole: Proton Pump Inhibitors may decrease the serum concentration of Posaconazole. Consider therapy modification

Raltegravir: Proton Pump Inhibitors may increase the serum concentration of Raltegravir. Monitor therapy

Rilpivirine: Proton Pump Inhibitors may decrease the serum concentration of Rilpivirine. Avoid combination

Riociguat: Proton Pump Inhibitors may decrease the serum concentration of Riociguat. Monitor therapy

Risedronate: Proton Pump Inhibitors may diminish the therapeutic effect of Risedronate. Proton Pump Inhibitors may increase the serum concentration of Risedronate. This applies specifically to use of delayed-release risedronate. Avoid combination

Saquinavir: Proton Pump Inhibitors may increase the serum concentration of Saquinavir. Monitor therapy

Sarilumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Secretin: Proton Pump Inhibitors may diminish the diagnostic effect of Secretin. Specifically, use of PPIs may cause a hyperresponse in gastrin secretion in response to secretin stimulation testing, falsely suggesting gastrinoma. Management: Avoid concomitant use of proton pump inhibitors (PPIs) and secretin, and discontinue PPIs several weeks prior to secretin administration, with the duration of separation determined by the specific PPI. See full monograph for details. Consider therapy modification

Selexipag: CYP2C8 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Selexipag. CYP2C8 Inhibitors (Moderate) may increase the serum concentration of Selexipag. Management: If initiating selexipag in a patient on a moderate CYP2C8 inhibitor, consider a less frequent dosing regimen (ie, once daily). If initiating a moderate CYP2C8 inhibitor in a patient on selexipag, consider a selexipag dose reduction. Consider therapy modification

Siltuximab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

St John's Wort: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification

Tacrolimus (Systemic): Proton Pump Inhibitors may increase the serum concentration of Tacrolimus (Systemic). Management: Tacrolimus dose adjustment may be required. Rabeprazole, pantoprazole, or selected H2-receptor antagonists (i.e., ranitidine or famotidine) may be less likely to interact. Genetic testing may predict patients at highest risk. Consider therapy modification

Tipranavir: May decrease the serum concentration of Proton Pump Inhibitors. These data are derived from studies with Ritonavir-boosted Tipranavir. Monitor therapy

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Velpatasvir: Proton Pump Inhibitors may decrease the serum concentration of Velpatasvir. Avoid combination

Voriconazole: May increase the serum concentration of Proton Pump Inhibitors. Proton Pump Inhibitors may increase the serum concentration of Voriconazole. Management: In patients receiving omeprazole 40 mg/day or greater, reduce omeprazole dose by half when initiating voriconazole. Monitor therapy

Test Interactions

Chromogranin A: PPIs may falsely elevate serum chromogranin A (CgA) levels. The increased CgA level may cause false-positive results in the diagnosis of a neuroendocrine tumor. Temporarily stop rabeprazole ≥14 days prior to assessing CgA level; repeat level if initially elevated; use the same laboratory for all testing of CgA levels.

Secretin stimulation test: Hyper-response in gastrin secretion in adults in response to secretin stimulation test has been reported, falsely suggesting gastrinoma. Temporarily stop treatment at least 14 days before assessing to allow gastrin levels to return to baseline.

Tetrahydrocannabinol urine screening tests: False positive urine screening tests for tetrahydrocannabinol (THC) have been reported. Alternative confirmatory methods should be considered to verify positive results.

Adverse Reactions

As reported in adults unless otherwise noted.

1% to 10%:

Cardiovascular: Peripheral edema (≥2%)

Central nervous system: Headache (≥2%; children & adolescents: 5% to 10%), pain (3%), dizziness (≥2%)

Gastrointestinal: Diarrhea (2%; children and adolescents: 5% to 21%), nausea (children & adolescents: 2% to 9%), abdominal pain (children: 16%; adolescents: 4%; adults: <2%), vomiting (children: 10% to 14%; adolescents: 4%), flatulence (3%), xerostomia (≥2%), constipation (2%)

Hepatic: Hepatic encephalopathy (≥2%), hepatitis (≥2%), increased liver enzymes (≥2%)

Infection: Increased susceptibility to infection (2%)

Neuromuscular & skeletal: Arthralgia (≥2%), myalgia (≥2%)

Respiratory: Pharyngitis (3%)

<1%, postmarketing, and/or case reports: Agranulocytosis, angioedema, bone fracture, bullous rash, Clostridium difficile associated diarrhea (CDAD), coma, cutaneous lupus erythematous, delirium, disorientation, dysgeusia, erythema multiforme, hemolytic anemia, hepatotoxicity (idiosyncratic) (Chalasani 2014), hyperammonemia, hypomagnesemia, increased thyroid stimulating hormone level, interstitial nephritis, jaundice, leukopenia, pancytopenia, pneumonia, pruritus, renal disease (chronic; Lazarus 2016), rhabdomyolysis, Stevens-Johnson syndrome, systemic lupus erythematosus, thrombocytopenia, toxic epidermal necrolysis

Warnings/Precautions

Concerns related to adverse effects:

• Atrophic gastritis: Long-term omeprazole therapy has caused atrophic gastritis (by biopsy); this may also occur with rabeprazole.

• Carcinoma: No reports of adenomatoid, dysplastic or neoplastic changes of enterochromaffin-like (ECL) cells in the gastric mucosa have occurred.

Clostridium difficile-associated diarrhea (CDAD): Use of proton pump inhibitors (PPIs) may increase risk of CDAD, especially in hospitalized patients; consider CDAD diagnosis in patients with persistent diarrhea that does not improve. Use the lowest dose and shortest duration of PPI therapy appropriate for the condition being treated.

• Cutaneous and systemic lupus erythematosus: Has been reported as new onset or exacerbation of existing autoimmune disease; most cases were cutaneous lupus erythematosus (CLE), most commonly, subacute CLE (occurring within weeks to years after continuous therapy). Systemic lupus erythematosus (SLE) is less common (typically occurs within days to years after initiating treatment) and occurred primarily in young adults up to the elderly. Discontinue therapy if signs or symptoms of CLE or SLE occur and refer to specialist for evaluation; most patients improve 4 to 12 weeks after discontinuation of rabeprazole.

• Fractures: Increased incidence of osteoporosis-related bone fractures of the hip, spine, or wrist may occur with proton pump inhibitor (PPI) therapy. Patients on high-dose (multiple daily doses) or long-term therapy (≥1 year) should be monitored. Use the lowest effective dose for the shortest duration of time, use vitamin D and calcium supplementation, and follow appropriate guidelines to reduce risk of fractures in patients at risk.

• Gastrointestinal infection (eg, Salmonella, Campylobacter): Use of proton pump inhibitors may increase risk of these infections.

• Hypomagnesemia: Reported rarely, usually with prolonged PPI use of ≥3 months (most cases >1 year of therapy). May be symptomatic or asymptomatic; severe cases may cause tetany, seizures, and cardiac arrhythmias. Consider obtaining serum magnesium concentrations prior to beginning long-term therapy, especially if taking concomitant digoxin, diuretics, or other drugs known to cause hypomagnesemia; and periodically thereafter. Hypomagnesemia may be corrected by magnesium supplementation, although discontinuation of rabeprazole may be necessary; magnesium levels typically return to normal within 1 week of stopping.

• Interstitial nephritis: Acute interstitial nephritis has been observed in patients taking PPIs; may occur at any time during therapy and is generally due to an idiopathic hypersensitivity reaction. Discontinue if acute interstitial nephritis develops.

• Vitamin B12 deficiency: Prolonged treatment (>3 years) may lead to vitamin B12 malabsorption and subsequent vitamin B12 deficiency. The magnitude of the deficiency is dose-related and the association is stronger in females and those younger in age (<30 years); prevalence is decreased after discontinuation of therapy (Lam 2013).

Disease-related concerns:

• Gastric malignancy: Relief of symptoms does not preclude the presence of a gastric malignancy.

• Hepatic impairment: Avoid use in patients with severe hepatic impairment; if treatment is necessary monitor for adverse reactions.

Concurrent drug therapy issues:

• Clopidogrel: Proton pump inhibitors (PPIs) may diminish the therapeutic effect of clopidogrel, thought to be due to reduced formation of the active metabolite of clopidogrel. The manufacturer of clopidogrel recommends either avoidance of both omeprazole (even when scheduled 12 hours apart) and esomeprazole or use of a PPI with comparatively less effect on the active metabolite of clopidogrel. Avoidance of rabeprazole appears prudent due to potent in vitro CYP2C19 inhibition (Li 2004) and lack of sufficient comparative in vivo studies with other PPIs. In contrast to these warnings, others have recommended the continued use of PPIs, regardless of the degree of inhibition, in patients with a history of GI bleeding or multiple risk factors for GI bleeding who are also receiving clopidogrel since no evidence has established clinically meaningful differences in outcome; however, a clinically-significant interaction cannot be excluded in those who are poor metabolizers of clopidogrel (Abraham 2010; Levine 2011).

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Other warnings/precautions:

• Appropriate use: Helicobacter pylori eradication: Short-term combination therapy (≤7 days) has been associated with a higher incidence of treatment failure. The American College of Gastroenterology recommends 10 to 14 days of therapy (triple or quadruple) for eradication of H. pylori (Chey 2007).

Monitoring Parameters

Magnesium levels (prior to initiation of therapy and periodically thereafter) in patients on long-term treatment or those taking digoxin, diuretics, or other drugs that cause hypomagnesemia; susceptibility testing recommended in patients who fail H. pylori eradication regimen.

Pregnancy Considerations

Available studies have not shown an increased risk of major birth defects following maternal use of proton pump inhibitors during pregnancy; however, information specific to rabeprazole is limited (Pasternak 2010); most information available for omeprazole. When treating GERD in pregnancy, PPIs may be used when clinically indicated (Katz 2013).

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience headache, nausea, vomiting, diarrhea, constipation, flatulence, or pharyngitis. Have patient report immediately to prescriber signs of low magnesium (mood changes; muscle pain or weakness; muscle cramps or spasms; seizures; tremors; lack of appetite; severe nausea or vomiting; or an abnormal heartbeat), signs of kidney problems (urinary retention, hematuria, change in amount of urine passed, or weight gain), signs of lupus (rash on the cheeks or other body parts, sunburn easy, muscle or joint pain, angina or shortness of breath, or swelling in the arms or legs), severe dizziness, passing out, severe abdominal pain, bone pain, chills, excessive weight loss, severe loss of strength and energy, signs of Clostridium difficile (C. diff)-associated diarrhea (abdominal pain or cramps, severe diarrhea or watery stools, or bloody stools), or signs of Stevens-Johnson syndrome/toxic epidermal necrolysis (red, swollen, blistered, or peeling skin [with or without fever]; red or irritated eyes; or sores in mouth, throat, nose, or eyes) (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

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