Rabeprazole

Pharmacologic Category

Proton Pump Inhibitor; Substituted Benzimidazole

Dosing: Adult

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

Dyspepsia (off-label use): Oral: 20 mg once daily for up to 8 weeks (Dewan 2011, Iwakiri 2013; Pinto-Sanchez 2017)

Gastric ulcer (treatment) (off-label use): Oral: 20 mg once daily (Cloud 1998; Dekkers 1998) for generally 8 weeks based on healing and/or ulcer complications (Boparai 2008; Wolfe 2000).

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 (nonerosive): 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

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.

NSAID-induced ulcer prophylaxis (off-label use): Oral: 5 to 20 mg once daily for 12 to 24 weeks (Iwakiri 2014; Sanuki 2012)

Prevention of recurrent gastric or duodenal ulcer bleeding postendoscopy (off-label use): Oral: 20 mg twice daily for 72 hours (Kim 2012)

Discontinuation of therapy: Oral: Some experts recommend a step-down approach in order to avoid worsening or rebound symptoms. One recommendation is to decrease the dose by 50% over 2 weeks to 4 weeks. If the patient is already on the lowest possible dose, alternate day therapy may be considered. If symptoms worsen during treatment or after discontinuation, patient should be re-evaluated (Kim 2018).

* See Dosage and Administration in AHFS Essentials for additional information.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Renal Impairment: Adult

No dosage adjustment necessary.

Dosing: Hepatic Impairment: Adult

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.

Dosing: Pediatric

GERD, symptomatic: Note: Guidelines recommend a 4- to 8-week treatment course; if improvement seen after 4 to 8 weeks, consider possible wean; if no response after 4 to 8 weeks, reevaluate diagnosis and consider referral to pediatric GI specialist (NASPGHAN/ESPGHAN [Rosen 2018]).

Infants: Limited data available: Oral: Sprinkle capsules: 5 to 10 mg once daily; dosing based on a double-blind, placebo-controlled trial which randomized patients aged 1 to 11 months (n=268) with symptomatic GERD to 10 mg, 5 mg, or placebo (n=88, n=90, n=90, respectively); the study found no difference in the degree of improvement with rabeprazole (at any dose) compared to those receiving placebo (Hussain 2014).

Children ≤11 years: Oral: Sprinkle capsules:

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

≥15 kg: 10 mg once daily; higher doses of 20 mg/day have also been described (Haddad 2014).

Children ≥12 years and Adolescents: Oral: Tablets: 20 mg once daily.

Helicobacter pylori eradication: Limited data available: Note: Usual duration of therapy is 14 days as part of triple therapy; use in combination with 2 antimicrobials (eg, clarithromycin, metronidazole, amoxicillin); preferred agents determined by susceptibility. Bismuth may be added to regimens as an alternative if resistance is present or susceptibility is unknown (NASPGHAN/ESPGHAN [Jones 2017]).

Children and Adolescents <16 years: Note: Dosing based on a pharmacokinetic modeling study to determine a dose that achieved AUC comparable to adults receiving 20 mg twice daily (Kimko 2015).

6 to <10 kg: Oral: 10 mg twice daily.

10 to <30 kg: Oral: 15 mg twice daily.

≥30 kg: Oral: 20 mg twice daily.

Discontinuation of therapy: Oral: Based on experience in adults, some experts recommend a step-down approach in order to avoid worsening or rebound symptoms. One recommendation is to decrease the dose by 50% over 2 to 4 weeks. If the patient is already on the lowest possible dose, alternate day therapy may be considered. If symptoms worsen during treatment or after discontinuation, patient should be reevaluated (Kim 2018).

Dosing: Renal Impairment: Pediatric

Children and Adolescents: There are no dosage adjustments provided in the manufacturer's labeling; however, pharmacokinetic studies in adults with end-stage renal disease (CrCl ≤5 mL/minute) on hemodialysis showed no clinically significant pharmacokinetic differences.

Dosing: Hepatic Impairment: Pediatric

Children and Adolescents:

Mild to moderate: No dosage adjustments are recommended

Severe impairment: Avoid use; if treatment is necessary, monitor for adverse reactions.

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 (nonerosive): 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.

* See Uses in AHFS Essentials for additional information.

Use: Off-Label: Adult

DyspepsiaLevel of Evidence [B, G]

Data from a phase 2, multicenter, double-blinded, placebo-controlled trial as well as from a prospective multicenter study supports the use of rabeprazole for the treatment of dyspepsia ^Ref. In addition, data from a systematic review support the use of rabeprazole for treatment of patients with ulcer and reflux-like functional dyspepsia ^Ref.

Based on the American College of Gastroenterology (ACG) and Canadian Association of Gastroenterology (CAG) guidelines for the management of dyspepsia, the use of rabeprazole is effective and recommended treatment for dyspepsia and functional dyspepsia in patients <60 years of age who are H. pylori negative or remain symptomatic after H. pylori eradication therapy ^Ref.

Gastric ulcer (treatment)Level of Evidence [B]

Data from a randomized, placebo-controlled, double-blind study and a randomized, double-blind, active-comparator study support the use of rabeprazole in the treatment of active gastric ulcers ^Ref.

NSAID-induced ulcer prophylaxisLevel of Evidence [B, G]

According to the American College of Gastroenterology 2009 Guidelines for Prevention of NSAID-Related Ulcer Complications, proton pump inhibitors are effective and recommended in the prophylaxis of gastric and duodenal ulcers in patients receiving NSAID therapy ^Ref.

Data from randomized, double-blind, active-controlled trials support the use of rabeprazole in the prevention of NSAID-induced peptic ulcers ^Ref.

Prevention of recurrent gastric or duodenal ulcer bleeding postendoscopyLevel of Evidence [B]

Data from a small prospective, randomized, controlled trial support the use of high-dose rabeprazole to decrease the risk of rebleeding postendoscopy for acute bleeding peptic ulcers ^Ref. Additional trials may be necessary to further define the role of rabeprazole in this setting.

Stress ulcer prophylaxis in critically-ill patientsLevel of Evidence [G]

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 H_2-receptor antagonist is recommended in sepsis or septic shock patients who have GI bleeding risk factors.

Level of Evidence Definitions

Level of Evidence Scale

Class and Related Monographs

Proton Pump Inhibitors

Clinical Practice Guidelines

Barrett Esophagus:

ACG, “Diagnosis and Management of Barrett's Esophagus,” January 2016

Critical Care:

“Surviving Sepsis Campaign: International Guidelines for the Management of Severe Sepsis and Septic Shock: 2016,” March 2017

Drug-Induced Liver Injury:

American College of Gastroenterology (ACG), “2014 ACG Guideline for Idiosyncratic Drug-induced Liver Injury,” July 2014

Dyspepsia:

ACG/CAG “Guidelines for the Management of Dyspepsia,” June 2017

Gastroesophageal Reflux Disease:

ACG, "Guidelines for the Diagnosis and Management of Gastroesophageal Reflux Disease,” March 2013

AGA, "Medical Position Statement on the Management of Gastroesophageal Reflux Disease,” October 2008

Helicobacter pylori Infection:

“ACG Guideline on the Management of Helicobacter Pylori Infection,” August 2007

“ACG Guideline on the Treatment of Helicobacter pylori Infection,” February 2017

NSAID-Related Ulcers:

“ACG Guidelines for Prevention of NSAID-Related Ulcer Complications,” February 2009

Proton Pump Inhibitors & Thienopyridines:

"2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention,” November 2011

“ACCF/ACG/AHA 2010 Expert Consensus Document on the Concomitant Use of Proton Pump Inhibitors and Thienopyridines,” December 2010

“The Use of Antiplatelet Therapy in the Outpatient Setting: Canadian Cardiovascular Society Guidelines,” 2011

Sepsis:

“Surviving Sepsis Campaign: International Guidelines for the Management of Severe Sepsis and Septic Shock: 2012,” February 2013

Administration: Oral

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.

Administration: Pediatric

Oral: May administer with an antacid.

Sprinkle capsules: Administer 30 minutes before a meal. Open capsule and sprinkle 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: May be administered without regard to food; best if taken 30 minutes before a meal when treating GERD (Lightdale 2013). Tablets should be swallowed whole, do not chew, crush, or split.

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/Stability

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

Medication Patient Education with HCAHPS Considerations

What is this drug used for?

• It is used to treat gastroesophageal reflux disease (GERD; acid reflux).

• It is used to treat heartburn.

• It is used to treat or prevent GI (gastrointestinal) ulcers caused by infection.

• It is used to treat or prevent ulcers of the swallowing tube (esophagus).

• It is used to treat syndromes caused by lots of stomach acid.

• It may be given to you for other reasons. Talk with the doctor.

Frequently reported side effects of this drug

• Headache

• Abdominal pain

• Nausea

• Vomiting

• Diarrhea

• Constipation

• Passing gas

• Sore throat

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Low magnesium like mood changes; muscle pain or weakness; muscle cramps or spasms; seizures; tremors; lack of appetite; severe nausea or vomiting; or an abnormal heartbeat

• Kidney problems like not able to pass urine, blood in the urine, change in amount of urine passed, or weight gain

• Lupus like rash on the cheeks or other body parts, sunburn easy, muscle or joint pain, chest pain or shortness of breath, or swelling in the arms or legs

• Severe dizziness

• Passing out

• Bone pain

• Chills

• Excessive weight loss

• Severe loss of strength and energy

• Clostridioides (formerly Clostridium) difficile (C. diff)-associated diarrhea like abdominal pain or cramps, severe diarrhea or watery stools, or bloody stools

• Stevens-Johnson syndrome/toxic epidermal necrolysis like red, swollen, blistered, or peeling skin (with or without fever); red or irritated eyes; or sores in mouth, throat, nose, or eyes

• Signs of a significant reaction like 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. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Medication Safety Issues

Sound-alike/look-alike issues:

Geriatric Patients: High-Risk Medication:

Medication Guide and/or Vaccine Information Statement (VIS)

An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:

Aciphex DR: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020973s039lbl.pdf#page=34

Aciphex Sprinkle: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/204736s010lbl.pdf#page=21

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

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.

• Clostridioides (formerly 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.

• Fundic gland polyps: Use of PPIs increases risk of fundic gland polyps, especially with long term use (>1 year). May occur without symptoms but nausea, vomiting, or abdominal pain may occur; gastrointestinal bleeding and/or anemia may occur with ulcerated polyps. Diagnosis of polyps may also increase risk for small intestinal blockage. Use the lowest dose and shortest duration of PPI therapy appropriate for the condition being treated.

• 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 of age); 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: 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 2017).

* See Cautions in AHFS Essentials for additional information.

Geriatric Considerations

No difference in efficacy or safety was noted in elderly subjects as compared to younger subjects. No dosage adjustment is necessary in the elderly.

Use has been associated with C. difficile infection, bone loss and fractures, and hypomagnesemia.

Warnings: Additional Pediatric Considerations

Use of gastric acid inhibitors, including proton pump inhibitors and H₂ blockers, has been associated with an increased risk for development of acute gastroenteritis and community-acquired pneumonia in pediatric patients 4 to 36 months of age (Canani 2006).

Pregnancy Considerations

Recommendations for the treatment of GERD in pregnancy are available. As in nonpregnant patients, lifestyle modifications followed by other medications are the initial treatments (Body 2016; Huerta-Iga 2016; Katz 2013; van der Woude 2014). Based on available data, PPIs may be used when clinically indicated (use of agents with more data in pregnancy may be preferred) (Body 2016; Matok 2012; Pasternak 2010; van der Woude 2014).

Breast-Feeding Considerations

It is not known if rabeprazole is present in breast milk.

According to the manufacturer, the decision to continue or discontinue breastfeeding during therapy should take into account the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother.

Briggs' Drugs in Pregnancy & Lactation

• Rabeprazole

Adverse Reactions

>10%: Gastrointestinal: Diarrhea (children and adolescents: 5% to 21%; adults: <2%), abdominal pain (children: 16%; adolescents and adults: ≤4%), vomiting (children: 10% to 14%; adolescents: 4%)

1% to 10%:

Cardiovascular: Peripheral edema (adults: <2%)

Central nervous system: Headache (children and adolescents: 5% to 10% adults: <2%), pain (adults: 3%), dizziness (adults: <2%)

Gastrointestinal: Nausea (children and adolescents: 2% to 9%), flatulence (adults: 3%), constipation (adults: 2%), xerostomia (<2%)

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

Infection: Infection (adults: 2%)

Neuromuscular & skeletal: Arthralgia (adults: <2%), myalgia (adults: <2%)

Respiratory: Pharyngitis (adults: 3%)

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

* See Cautions in AHFS Essentials for additional information.

Allergy and Idiosyncratic Reactions

• Proton Pump Inhibitor, Benzimidazole Allergy

Metabolism/Transport Effects

Substrate of CYP2C19 (major), CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits OAT1/3

Drug Interactions Open Interactions

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

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

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

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

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

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

Capecitabine: Proton Pump Inhibitors may diminish the therapeutic effect of Capecitabine. Risk C: 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. Risk D: Consider therapy modification

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

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

CYP2C19 Inducers (Moderate): May decrease the serum concentration of CYP2C19 Substrates (High risk with Inducers). Risk C: Monitor therapy

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. Risk D: Consider therapy modification

CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: 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. Risk D: Consider therapy modification

Cysteamine (Systemic): Proton Pump Inhibitors may diminish the therapeutic effect of Cysteamine (Systemic). Risk C: 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). Risk D: 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). Risk D: Consider therapy modification

Dacomitinib: Proton Pump Inhibitors may decrease the serum concentration of Dacomitinib. Management: Avoid concurrent use of dacomitinib with proton pump inhibitors. Antacids may be used. Histamine H2-receptor antagonists (HR2A) may be used if dacomitinib is given at least 6 hours before or 10 hours after the H2RA. Risk X: Avoid combination

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. Risk X: Avoid combination

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

Dichlorphenamide: OAT1/3 Inhibitors may increase the serum concentration of Dichlorphenamide. Risk C: Monitor therapy

Doxycycline: Proton Pump Inhibitors may decrease the bioavailability of Doxycycline. Risk C: 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. Risk D: 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. Risk D: Consider therapy modification

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

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

Fluconazole: May increase the serum concentration of Proton Pump Inhibitors. Risk C: 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. Risk D: Consider therapy modification

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

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

Itraconazole: Proton Pump Inhibitors may increase the serum concentration of Itraconazole. Proton Pump Inhibitors may decrease the serum concentration of Itraconazole. Management: Exposure to Tolsura brand itraconazole may be increased by PPIs; consider itraconazole dose reduction. Exposure to Sporanox brand itraconazole capsules may be decreased by PPIs. Give Sporanox brand itraconazole at least 2 hrs before or 2 hrs after PPIs Risk D: Consider therapy modification

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

Ketoconazole (Systemic): Proton Pump Inhibitors may decrease the absorption of Ketoconazole (Systemic). Ketoconazole (Systemic) may increase the serum concentration of Proton Pump Inhibitors. Management: Administer ketoconazole with an acidic beverage, such as non-diet cola, to increase gastric acidity and improve absorption if concomitant use with proton pump inhibitors is necessary. Risk D: 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. Risk D: 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. Risk D: Consider therapy modification

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

Mycophenolate: Proton Pump Inhibitors may decrease the serum concentration of Mycophenolate. Specifically, concentrations of the active mycophenolic acid may be reduced. Risk C: 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. Risk X: Avoid combination

Neratinib: Proton Pump Inhibitors may decrease the serum concentration of Neratinib. Specifically, proton pump inhibitors may reduce neratinib absorption. Risk X: 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. Risk D: Consider therapy modification

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

Pexidartinib: Proton Pump Inhibitors may decrease the serum concentration of Pexidartinib. Management: If acid-reduction is needed, consider administering an antacid 2 hours before or after pexidartinib, or administer pexidartinib 2 hours before or 10 hours after an H2 receptor antagonist. Risk X: Avoid combination

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

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

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

Riociguat: Proton Pump Inhibitors may decrease the serum concentration of Riociguat. Risk C: 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. Risk D: Consider therapy modification

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

Sarilumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: 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. Risk D: Consider therapy modification

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

SORAfenib: Proton Pump Inhibitors may decrease the absorption of SORAfenib. Risk C: Monitor therapy

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. Risk D: Consider therapy modification

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

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

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

Voriconazole: May increase the serum concentration of Proton Pump Inhibitors. Proton Pump Inhibitors may increase the serum concentration of Voriconazole. Risk C: Monitor therapy

Food Interactions

Prolonged treatment (≥2 years) may lead to malabsorption of dietary vitamin B₁₂ and subsequent vitamin B₁₂ deficiency (Lam, 2013).

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.

Genes of Interest

• CYP2C19 - Rabeprazole
• Cytochrome P450 3A4

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.

Advanced Practitioners Physical Assessment/Monitoring

Assess those medications requiring acid environment for absorption. Monitor reduction in symptoms.

Nursing Physical Assessment/Monitoring

Assess those medications requiring acid environment for absorption. Monitor reduction in symptoms.

Dosage Forms: US

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)]

Generic: 10 mg

Tablet Delayed Release, Oral, as sodium:

Aciphex: 20 mg

Generic: 20 mg

Dosage Forms: Canada

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

Tablet Delayed Release, Oral:

Pariet: 10 mg

Generic: 10 mg

Tablet Delayed Release, Oral, as sodium:

Pariet: 20 mg

Generic: 20 mg

Anatomic Therapeutic Chemical (ATC) Classification

• A02BC04

Generic Available (US)

Yes

Pricing: US

Capsule, sprinkles (AcipHex Sprinkle Oral)

5 mg (per each): $22.62

10 mg (per each): $24.13

Capsule, sprinkles (RABEprazole Sodium Oral)

10 mg (per each): $49.67

Tablet, EC (Aciphex Oral)

20 mg (per each): $20.99

Tablet, EC (RABEprazole Sodium Oral)

20 mg (per each): $10.19 - $11.46

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Mechanism of Action

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

Pharmacodynamics/Kinetics

Onset of action: Within 1 hour

Duration: 24 hours

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

Protein binding: 96.3%

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

Bioavailability: Tablet: ~52%

Half-life elimination (dose dependent):

Children ≤11 years: 2.5 hours

Children ≥12 years and Adolescents: 20 mg tablet: 0.97 ± 0.19 hours (James 2007)

Adults: 1 to 2 hours

Time to peak, plasma:

Children ≤11 years: Sprinkle capsule: 2 to 4 hours

Children ≥12 years and Adolescents: 20 mg tablet: 4.1 ± 0.45 hours (James 2007)

Adults: Tablet: 2 to 5 hours; Sprinkle capsule: 1 to 6.5 hours

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

Pharmacodynamics/Kinetics: Additional Considerations

Hepatic function impairment: In mild to moderate hepatic impairment, AUC approximately doubled, total clearance decreased to less than half, and C_max increased ~20% (not statistically significant) and elimination half-life was 2- to 3-fold higher.

Geriatric: AUC values approximately doubled; C_max increased 60%.

Race: AUCs for Japanese men were 50% to 60% higher.

Local Anesthetic/Vasoconstrictor Precautions

No information available to require special precautions

Effects on Dental Treatment

No significant effects or complications reported

Effects on Bleeding

No information available to require special precautions

Related Information

• Beers Criteria 2019: Potentially Inappropriate Medication Use in Older Adults ≥65 Years of Age
• Oral Medications That Should Not Be Crushed or Altered

Index Terms

Pariprazole; Rabeprazole Sodium

FDA Approval Date

August 19, 1999

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Brand Names: International

Acifix (BD); Acilesol (SG); Aciprazol (AE, CY, IQ, IR, JO, KW, LY, OM, SA, SY, YE); Ares (HR); Barole (PH); Bepra (EG); Gastrodine (CL); Gelbra (ES); Happi (LK); Hygigastin (EG); Noflux (CZ); Pacredo (EG); Paliell (KR); Paramet (KR); Parbezol (AU); Paricel (BD); Pariet (AE, AR, AT, AU, BB, BE, BG, BH, BM, BO, BR, BS, CH, CN, CO, CR, CY, DE, DK, DO, EG, ES, FI, FR, GB, GR, GT, GY, HK, HN, ID, IE, IQ, IR, IS, IT, JM, JO, JP, KR, KW, LB, LT, LU, LY, MT, MX, MY, NI, NL, NZ, OM, PA, PE, PH, PL, PR, PT, PY, RU, SA, SE, SG, SR, SV, SY, TH, TR, TT, TW, UY, VE, VN, YE, ZA, ZW); Parzol (AU); Promto (VN); Rabe (BD, LK); Rabeact (LK); Rabeact-20 (HK); Rabec (AR, LB); Rabecid (PK); Rabegen (KR); Rabekind (TZ); Rabeloc (IN, VN); Rabeol (KR); Raberin (KR); Rabesta (KR, PH); Rabestad (HK); Rabet (KR); Rabetra (HK); Rabezole (BH, LB, QA, SA); Rabiet (KR); Rabister (KR); Rabium (BD); Rabtas (ZW); Rapeed (PH); Rapoxol (CZ); Rapzol (PH); Rasonix (BD); Raxium (VN); Razit (AU); Razole (IE); Relitaz (RO); Renom (LK); Risol (LK); Veloz (BH); Zabep (AU); Zulbex (CZ, HR, LV, RO)

Last Updated 2/20/20