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RABEprazole (Monograph)

Brand name: AcipHex
Drug class: Proton-pump Inhibitors
- Antiulcer Agents
- Gastric Antisecretory Agents
- Acid-pump Inhibitors
VA class: GA900
Chemical name: 2-[[[4-(3-Methoxypropoxy)-3-methyl-2-pyridyl]methyl]sulfinyl]-benzimidazole sodium
Molecular formula: C18H20N3NaO3S
CAS number: 117976-90-6

Medically reviewed by Drugs.com on Feb 5, 2025. Written by ASHP.

Introduction

Acid- or proton-pump inhibitor; gastric antisecretory agent.1 2 3 4 5 6

Uses for RABEprazole

Gastroesophageal Reflux (GERD)

Short-term treatment of symptomatic GERD (e.g., heartburn) in patients without erosive esophagitis.1

Short-term treatment of erosive esophagitis in patients with GERD.1 2 3 15 18

Maintain healing and decrease recurrence of erosive esophagitis.1 2 3

Duodenal Ulcer

Short-term treatment of active duodenal ulcer.1 2 3 17

Treatment of Helicobacter pylori infection and duodenal ulcer disease.1 Used in conjunction with amoxicillin and clarithromycin (triple therapy).1

Pathologic GI Hypersecretory Conditions

Long-term treatment of pathologic GI hypersecretory conditions (e.g., Zollinger-Ellison syndrome).1 3

Crohn’s Disease-associated Ulcers

Some evidence for use of proton-pump inhibitors (e.g., omeprazole) for gastric acid suppressive therapy as an adjunct in the management of upper GI Crohn’s disease† [off-label], including esophageal† [off-label], gastroduodenal† [off-label], and jejunoileal† [off-label] disease.27 28 29 31 32 33

RABEprazole Dosage and Administration

Administration

Oral Administration

Administer orally; may give without regard to meals, but manufacturer recommends administration after morning meal in patients with duodenal ulcer.1

When used in combination with clarithromycin and amoxicillin for treatment of H. pylori infection and duodenal ulcer disease, take all 3 drugs twice daily with morning and evening meals.1

Swallow tablets intact; do not chew, crush, or split.1

Antacids may be used concomitantly as needed for pain relief.1 19

Dosage

Available as rabeprazole sodium; dosage expressed in terms of the salt.1

Pediatric Patients

GERD
Symptomatic GERD
Oral

Adolescents ≥12 years of age: 20 mg once daily for up to 8 weeks.1

Adults

GERD
GERD without Erosive Esophagitis
Oral

20 mg once daily for 4 weeks; may give additional 4 weeks if symptoms are not completely resolved.1

Treatment of Erosive Esophagitis
Oral

20 mg once daily1 2 15 18 for 4–8 weeks.1 15 If not healed after 8 weeks, consider additional 8 weeks of therapy (up to 16 weeks for a single course).1

Maintenance of Healing of Erosive Esophagitis
Oral

20 mg once daily.1 2 15 18 Chronic, lifelong therapy may be appropriate.26

Duodenal Ulcer
Treatment of Active Duodenal Ulcer
Oral

20 mg once daily for up to 4 weeks;1 2 17 18 some patients may require additional therapy.1

Helicobacter pylori Infection and Duodenal Ulcer Disease
Oral

Triple therapy: 20 mg twice daily for 7 days in conjunction with amoxicillin and clarithromycin.1

Pathologic GI Hypersecretory Conditions (e.g., Zollinger-Ellison Syndrome)
Oral

60 mg once daily.1 Dosages up to 100 mg once daily or 60 mg twice daily have been used.1 Divided doses may be required.1 Adjust dosage as needed, continue treatment as long as necessary.1 Has been used continuously for up to 1 year.1

Detailed Rabeprazole dosage information

Cautions for RABEprazole

Contraindications

Warnings/Precautions

Gastric Malignancy

Response to rabeprazole does not preclude presence of occult gastric neoplasm.1

Clostridium difficile Infection

Proton-pump inhibitors associated with possible increased (1.4–2.75 times) risk of Clostridium difficile infection, including C. difficile-associated diarrhea and colitis (CDAD; also known as antibiotic-associated diarrhea and colitis or pseudomembranous colitis).335 336 339 340 Many patients also had other risk factors for CDAD.335 May be severe; colectomy and, rarely, death reported.335

Use the lowest effective dosage and shortest duration of therapy appropriate for the patient's clinical condition.335

Consider CDAD if persistent diarrhea develops and manage accordingly; initiate supportive therapy (e.g., fluid and electrolyte management), anti-infective therapy directed against C. difficile (e.g., metronidazole, vancomycin), and surgical evaluation as clinically indicated.335 336

Respiratory Effects

Administration of proton-pump inhibitors has been associated with an increased risk for developing certain infections (e.g., community-acquired pneumonia).35 36

Bone Fracture

Several observational studies suggest that use of proton-pump inhibitors, particularly in high dosages (i.e., multiple daily doses) and/or for prolonged periods of time (i.e., ≥1 year), may be associated with increased risk of osteoporosis-related fractures of the hip, wrist, or spine.1 39 300 301 302 303 304 305 Magnitude of risk is unclear;39 300 301 302 303 304 305 310 causality not established.305 FDA is continuing to evaluate this safety concern.305

Use the lowest effective dosage and shortest duration of therapy appropriate for the patient’s clinical condition.1 39 301 303 305 307

Individuals at risk for osteoporosis-related fractures should receive an adequate intake of calcium and vitamin D; assess and manage these patients’ bone health according to current standards of care.1 39 303 305 307

Hypomagnesemia

Hypomagnesemia, symptomatic and asymptomatic, reported rarely in patients receiving long-term therapy (≥3 months or, in most cases, >1 year) with proton-pump inhibitors, including rabeprazole.1 317 318 319 320 321 322 323 324 325 326 327 328 329 330 Serious adverse effects include tetany, seizures, tremors, carpopedal spasm, arrhythmias (e.g., atrial fibrillation, supraventricular tachycardia), and abnormal QT interval.1 318 319 321 322 323 325 327 328 329 Paresthesia, muscle weakness, muscle cramps, lethargy, fatigue, and unsteadiness may occur.319 320 321 325 330 Most patients required magnesium replacement and discontinuance of the proton-pump inhibitor.1 317 319 321 322 323 324 325 326 327 330 Hypomagnesemia resolved within 1 week (median) following discontinuance and recurred within 2 weeks (median) of rechallenge.327

In patients expected to receive long-term proton-pump inhibitor therapy or in patients currently receiving digoxin or drugs that may cause hypomagnesemia (e.g., diuretics), consider measuring serum magnesium concentrations prior to initiation of prescription proton-pump inhibitor therapy and periodically thereafter.1 319 326 327 328 330

Specific Populations

Pregnancy

Category B.1

Lactation

Not known whether rabeprazole is distributed into milk; discontinue nursing or the drug.1

Pediatric Use

Safety and efficacy for short-term treatment of symptomatic GERD established in adolescents 12–16 years of age.1 Pharmacokinetic and adverse effect profiles similar to those in adults.1

Safety and efficacy not established in children <12 years of age.1

Geriatric Use

No substantial differences in safety or efficacy relative to younger adults, but increased sensitivity cannot be ruled out.1

Hepatic Impairment

Use with caution in patients with severe impairment.1 21

Common Adverse Effects

Pain,1 pharyngitis,1 flatulence,1 infection,1 constipation.1

Drug Interactions

Metabolized in the liver, principally by CYP3A and 2C19 isoenzymes.1 7 8 9

Drugs Metabolized by Cytochrome P-450 Enzymes

No clinically important interactions with some drugs that are metabolized by CYP isoenzymes under single dose conditions; effects of rabeprazole have not been studied under steady-state conditions.1

Drugs that Cause Hypomagnesemia

Potential pharmacologic interaction (possible increased risk of hypomagnesemia).327 Consider monitoring magnesium concentrations prior to initiation of prescription proton-pump inhibitor therapy and periodically thereafter.1 327 (See Hypomagnesemia under Cautions.)

Specific Drugs

Drug

Interaction

Comments

Amoxicillin

Increased rabeprazole and 14-hydroxyclarithromycin AUC and plasma concentrations when administered with amoxicillin and clarithromycin1

Not expected to result in toxicity1

Antacids

No clinically important effects on rabeprazole pharmacokinetics1

Atazanavir

Possible altered oral absorption of atazanavir, resulting in decreased plasma atazanavir concentrations; possible loss of virologic response1 42

Manufacturer of rabeprazole states that concomitant administration with atazanavir is not recommended1

Antiretroviral treatment-naive patients: If a proton-pump inhibitor is used concomitantly with atazanavir, administer ritonavir-boosted atazanavir (atazanavir 300 mg and ritonavir 100 mg once daily with food); administer the proton-pump inhibitor approximately 12 hours before ritonavir-boosted atazanavir41 42

For treatment-naive patients, dosage of proton-pump inhibitor should not exceed omeprazole 20 mg daily (or equivalent)41 42

Antiretroviral treatment-experienced patients: Concomitant use of proton-pump inhibitors with atazanavir not recommended41 42

Clarithromycin

Increased rabeprazole and 14-hydroxyclarithromycin AUC and plasma concentrations when administered with amoxicillin and clarithromycin1

Not expected to result in toxicity1

Clopidogrel

Certain CYP2C19 inhibitors (e.g., omeprazole, esomeprazole) reduce exposure to clopidogrel’s active metabolite and decrease platelet inhibitory effect;223 224 225 228 232 233 236 350 potentially may reduce clopidogrel’s clinical efficacy219 220 221 224 229 230 234 235 236 237 238 240 311

Dexlansoprazole, lansoprazole, or pantoprazole had less effect on clopidogrel's antiplatelet activity than did omeprazole or esomeprazole224 350 351

Assess risks and benefits of concomitant proton-pump inhibitor and clopidogrel use in individual patients237 240 243 248 250

American College of Cardiology Foundation/American College of Gastroenterology/American Heart Association (ACCF/ACG/AHA) states that GI bleeding risk reduction with concomitant proton-pump inhibitor in patients with risk factors for GI bleeding (e.g., advanced age; concomitant use of warfarin, corticosteroids, or NSAIAs; H. pylori infection) may outweigh potential reduction in cardiovascular efficacy of antiplatelet treatment associated with a drug-drug interaction.311 In patients without such risk factors, ACCF/ACG/AHA states that risk/benefit balance may favor use of antiplatelet therapy without a proton-pump inhibitor.311

If concomitant therapy with a proton-pump inhibitor and clopidogrel is deemed necessary, consider using an agent with little or no CYP2C19-inhibitory activity;47 48 49 224 230 350 alternatively, consider using a histamine H2-receptor antagonist (ranitidine, famotidine, nizatidine)47 48 230 but not cimetidine (also a potent CYP2C19 inhibitor)232 233

Cyclosporine

Rabeprazole inhibited cyclosporine metabolism in vitro1

Diazepam

No pharmacokinetic interaction observed after single doses1

Digoxin

Hypomagnesemia (e.g., resulting from long-term use of proton-pump inhibitors) sensitizes the myocardium to digoxin and, thus, may increase risk of digoxin-induced cardiotoxic effects327 331

See table entry for gastric pH-dependent drugs

Consider monitoring magnesium concentrations prior to initiation of prescription proton-pump inhibitor therapy and periodically thereafter1 327

Diuretics (i.e., loop or thiazide diuretics)

Possible increased risk of hypomagnesemia1 327

Consider monitoring magnesium concentrations prior to initiation of prescription proton-pump inhibitor therapy and periodically thereafter1 327

Fosamprenavir

Use of esomeprazole with fosamprenavir (with or without ritonavir) did not substantially affect concentrations of amprenavir (active metabolite of fosamprenavir)345

No dosage adjustment required when proton-pump inhibitors used with fosamprenavir (with or without ritonavir)41 345

Gastric pH-dependent drugs (e.g., digoxin, ketoconazole)

Rabeprazole may alter drug absorption1

Monitor if used concomitantly1

Lopinavir

Lopinavir/ritonavir: Omeprazole had no clinically important effect on plasma concentrations or AUC of lopinavir41 344

No dosage adjustment required when proton-pump inhibitors used with lopinavir/ritonavir41

Methotrexate (high-dose)

Possible delayed clearance and increased serum concentrations of methotrexate and/or its metabolite hydroxymethotrexate; possible methotrexate toxicity1 334

Reported mainly with high-dose methotrexate (300 mg/m2 to 12 g/m2),1 but also reported with low dosages (e.g., 15 mg per week)

Manufacturer of rabeprazole recommends considering temporary discontinuance of proton-pump inhibitor therapy in some patients receiving high-dose methotrexate1

Some clinicians recommend withholding the proton-pump inhibitor for several days before and after administration of either high-dose or low-dose methotrexate or, alternatively, substituting a histamine H2-receptor antagonist for the proton-pump inhibitor334

Phenytoin

No pharmacokinetic interaction observed after single doses1

Raltegravir

Omeprazole increased peak plasma concentration and AUC of raltegravir41 348

No dosage adjustment recommended when proton-pump inhibitors used with raltegravir41 348

Rilpivirine

Omeprazole decreased plasma concentrations and AUC of rilpivirine41 343

Concomitant use of rilpivirine and proton-pump inhibitors contraindicated41 343

Saquinavir

Ritonavir-boosted saquinavir: Omeprazole increased peak plasma concentration and AUC of saquinavir41 346

Caution advised if proton-pump inhibitor used with ritonavir-boosted saquinavir; monitor for saquinavir toxicity41 346

Sucralfate

Possible delayed proton-pump inhibitor absorption and decreased bioavailability 34

Administer proton-pump inhibitor at least 30 minutes before sucralfate34

Theophylline

No pharmacokinetic interaction observed after single doses1

Warfarin

Potential for increased INR and PT1

Monitor PT and INR1
Rabeprazole drug interactions (more detail)

RABEprazole Pharmacokinetics

Absorption

Bioavailability

Absolute bioavailability with 20 mg dose is about 52%.1 Repeated dosing does not affect pharmacokinetics.1

Onset

Within 1 hour.1 23 Median inhibition of 24-hour gastric acidity is 88% of maximum after first dose.1

Food

High-fat meal may delay absorption but does not affect extent.1 20 23

Special Populations

AUC increased 50–60% in Japanese males receiving a different rabeprazole formulation.1

AUC doubled in patients with mild to moderate compensated cirrhosis.1 Peak plasma concentrations and AUCs increased 20% in patients with mild to moderate hepatic impairment.1

In geriatric patients, peak plasma concentration increased by 60% and AUCs doubled.1

Distribution

Extent

Not known whether rabeprazole crosses the placenta or is distributed into milk.1

Prolonged binding to gastric parietal proton pump enzyme.1 3

Plasma Protein Binding

Approximately 96%.1

Elimination

Metabolism

Metabolized in the liver, principally by CYP3A and CYP2C19.1 7 8 9 Principal thioether and sulphone metabolites found in plasma are inactive.1

Elimination Route

Excreted as metabolites in urine (90%); remainder in feces.1

Half-life

1–2 hours.1

Special Populations

In patients with mild to moderate compensated cirrhosis, elimination half-life was 2–3 times greater, and clearance decreased to less than one-half.1

In patients with poor CYP2C19 metabolizer phenotype, metabolism is slower than in those with extensive (or rapid) metabolizer phenotype.1

Stability

Storage

Oral

Tablets

25°C (may be exposed to 15–30°C).1 Protect from moisture.1

Actions

Advice to Patients

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

RABEprazole Sodium

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, delayed-release (enteric-coated)

20 mg

AcipHex

Eisai (also promoted by Janssen [formerly Ortho-McNeil-Janssen])

AHFS DI Essentials™. © Copyright 2025, Selected Revisions February 15, 2013. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Off-label: Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

1. Eisai Inc. and Janssen Pharmaceuticals Inc. AcipHex (rabeprazole sodium) delayed-release tablets prescribing information. Woodcliff Lake and Titusville, NJ; 2012 May

2. Prakash A, Faulds D. Rabeprazole. Drugs. 1998; 55:261-7. https://pubmed.ncbi.nlm.nih.gov/9506245

3. Richardson P, Hawkey CJ, Stack WA. Proton pump inhibitors. Pharmacology and rationale for use in gastrointestinal disorders. Drugs. 1998; 56:307-35. https://pubmed.ncbi.nlm.nih.gov/9777309

4. Morii M, Hamatani K, Takeguchi N. The proton pump inhibitor, E3810, binds to the N-terminal half of the α-subunit og gastric H+,K(+)-ATPase. Biochem Pharmacol. 1995; 16:1729-34.

5. Williams MP, Sercombe J, Hamilton MI et al. A placebo-controlled trial to assess the effects of 8 days of dosing with rabeprazole versus omeprazole on 24-h intragastric acidity and plasma gastrin concentrations in young healthy male subjects. Aliment Pharmacol Ther. 1998; 12:1079-89. https://pubmed.ncbi.nlm.nih.gov/9845397

6. Lew EA, Barbuti RC, Kovacs TO et al. An ascending single-dose safety and tolerance study of an oral formulation of rabeprazole (E3810). Aliment Pharmacol Ther. 1998; 12:667-72. https://pubmed.ncbi.nlm.nih.gov/9701531

7. VandenBranden M, Ring BJ, Binkley SN et al. Interaction of human liver cytochromes P450 in vitro with LY307640, a gastric proton pump inhibitor. Pharmacogenetics. 1996; 6:81-91. https://pubmed.ncbi.nlm.nih.gov/8845864

8. Yasuda S, Horai Y, Tomono Y et al. Comparison of the kinetic disposition and metabolism of E3810, a new proton inhibitor, and omeprazole in relation to S-mephenytoin 4′-hydroxylation status. Clin Pharmacol Ther. 1995; 58:143-54. https://pubmed.ncbi.nlm.nih.gov/7648764

9. Ishizaki T, Chiba K, Manabe K et al. Comparison of the interaction potential of a new proton pump inhibitor, E3810, versus omeprazole with diazepam in extensive and poor metabolizers of S-mephenytoin 4′-hydroxylation. Clin Pharmacol Ther. 1995; 58:155-64. https://pubmed.ncbi.nlm.nih.gov/7648765

10. Miwa H, Ohkura R, Murai T et al. Impact of rabeprazole, a new proton pump inhibitor, in triple therapy for Helicobacter pylori infection-comparison with omeprazole and lansoprazole. Aliment Pharmacol Ther. 1999; 13:741-6. https://pubmed.ncbi.nlm.nih.gov/10383502

11. Stack WA, Knifton A, Thirwell D et al. Safety and efficacy of rabeprazole in combination with four antibiotic regimens for eradication of Helicobacter pylori in patients with chronic gastritis with or without peptic ulceration. Am J Gastroenterol. 1998; 93:1909-13. https://pubmed.ncbi.nlm.nih.gov/9772054

12. Tsuchiya M, Imamura L, Park JB et al. Helicobacter pylori urease inhibition by rabeprazole, a proton pump inhibitor. Biol Pharm Bull. 1995; 18:1053-6. https://pubmed.ncbi.nlm.nih.gov/8535394

13. Park JB, Imamura L, Kobashi K. Kinetic studies of Helicobacter pylori urease inhibition by a novel proton pump inhibitor, rabeprazole. Biol Pharm Bull. 1996; 19:182-7. https://pubmed.ncbi.nlm.nih.gov/8850302

14. Hirai M, Azuma T, Ito S et al. A proton pump inhibitor, E3810, has antibacterial activity through niding to Helicobacter pylori. J Gastroenterol. 1995; 30:461-4. https://pubmed.ncbi.nlm.nih.gov/7550855

15. Dekkers CP, Beker JA, Thjodleifsson B et al for the European Rabeprazole Study Group. Double-blind comparison (correction of double-blind, placebo-controlled comparison) of rabeprazole 20 mg vs. omeprazole 20 mg in the treatment of erosive or ulcerative gastro-oesophageal reflux disease. Aliment Pharmacol Ther. 1999; 13:49-57. https://pubmed.ncbi.nlm.nih.gov/9892879

16. National Institutes of Health Consensus Development Group. Gastroesophageal reflux disease (hiatal hernia and heartburn). NIH Publication No. 94-882; 1994 Sep.

17. Dekkers CP, Beker JA, Thjodleifsson B et al. Comparison of rabeprazole 20 mg versus omperazole 20 mg in the treatment of active duodenal ulcer: a European multicentre study. Aliment Pharmacol Ther. 1999; 13:179-86. https://pubmed.ncbi.nlm.nih.gov/10102948

18. Cloud ML, Enas N, Humphries TJ et al for the Rabeprazole Study Group. Rabeprazole in treatment of acid peptic diseases: results of three placebo-controlled dose-response clinical trials in duodenal ulcer, gastric ulcer, and gastroesophageal reflux disease (GERD). Dig Dis Sci. 1998; 43:993-1000. https://pubmed.ncbi.nlm.nih.gov/9590413

19. Yasuda S, Higashi S, Murakami M et al. Antacids have no influence on the pharmacokinetics of rabeprazole, a new proton pump inhibitor, in healthy volunteers. Int J Clin Pharmacol Ther. 1999; 37:249-53. https://pubmed.ncbi.nlm.nih.gov/10363624

20. Yasuda S, Ohnishi A, Ogawa T et al. Pharmacokinetic properties of E3810, a new proton pump inhibitor, in healthy male volunteers. Int J Clin Pharmacol Ther. 1994; 32:466-73. https://pubmed.ncbi.nlm.nih.gov/7820329

21. Hoyumpa AM, Trevino-Alanis H, Grimes I et al. Rabeprazole: pharmacokinetics in patients with stable, compensated cirrhosis. Clin Ther. 1999; 21:691-701. https://pubmed.ncbi.nlm.nih.gov/10363734

22. Keane WF, Swan SK, Grimes I et al. Rabeprazole: pharmacokinetics and tolerability in patients with stable, end-stage renal failure. J Clin Pharmacol. 1999; 39:927-33. https://pubmed.ncbi.nlm.nih.gov/10471983

23. Eisai Inc. Teaneck, NJ: Personal communication.

24. Shinomura Y, Kanayama S, Miyazaki Y et al. A clinical study of the effects of E3810 (rabeprazole sodium) for the treatment of gastric and duodenal ulcers: a comparison of post-breakfast and bedtime dosing regimens. Mod Physician. 1994; 14:69-84.

25. Eisai Ltd. and Janssen-Cilag Pharmaceutica Inc. Pariet (rabeprazole sodium) gastro-resistant tablets product monograph. London, 1998 Sep. RabeprazoleRestricted Distribution/6

26. DeVault KR, Castell DO, Practice Parameters Committee of the American College of Gastroenterology. Updated guidelines for the diagnosis and treatment of gastroesophageal reflux disease. Am J Gastroenterol. 1999; 94:1434-42. https://pubmed.ncbi.nlm.nih.gov/10364004

27. Hanauer SB, Sandborn W, and the Practice Parameters Committee of the American College of Gastroenterology. Management of Crohn’s disease in adults: Practice Guidelines. Am J Gastroenterol. 2001; 96:635-43. https://pubmed.ncbi.nlm.nih.gov/11280528

28. Valori RM, Cockel R. Omeprazole for duodenal ulceration in Crohn’s disease. Br Med J. 1990; 300:438-9.

29. Bianchi G, Ardizzone S, Petrillo M et al. Omeprazole for peptic ulcer in Crohn’s disease. Am J Gastroenterol. 1991; 86: 245-6. https://pubmed.ncbi.nlm.nih.gov/1992643

30. Przemioslo RT, Mee AS. Omeprazole in possible esophageal Crohn’s disease. Dig Dis Sci. 1994; 39:1594-5. https://pubmed.ncbi.nlm.nih.gov/8026276

31. Dickinson JB. Is omeprazole helpful in inflammatory bowel disease? J Clin Gastroenterol. 1994; 18:317-9.

32. Abrahao LJ Jr., Abrahao LJ, Vargas C et al. [Gastoduodenal Crohn’s disease—report of 4 cases and review of the literature]. (Portuguese; with English abstract.) Arq Gastroenterol. 2001; 38:57-62.

33. Freston JW. Review article: role of proton pump inhibitors in non-H. pylori-related ulcers. Aliment Pharmacol Ther. 20001; 15(Suppl 2):2-5.

34. TAP. Prevacid (lansoprazole) delayed-release capsules, for delayed-release oral suspension and delayed-release orally disintegrating tablets prescribing information. Lake Forest, IL; 2003 Aug.

35. Laheij RJF, Sturkenboom MCJM, Hassing RJ et al. Risk of community-acquired pneumonia and use of gastric acid-suppressive drugs. JAMA. 2004; 292:1955-60. https://pubmed.ncbi.nlm.nih.gov/15507580

36. Gregor JC. Acid suppression and pneumonia.; a clinical indication for rational prescibing. JAMA. 2004;292:2012-3. Editorial.

37. AstraZeneca, Nexium (esomeprazole magnesium) delayed-release capsules prescribing information. Wilmington, DE; 2001 Aug.

38. TAP. Prevacid (lansoprazole) delayed-release capsules, for delayed-release oral suspension and delayed-release orally disintegrating tablets prescribing information. Lake Forest, IL; 2003 Aug.

39. Yang Y-X, Lewis JD, Epstein S et al. Long-term proton pump inhibitor therapy and risk of hip fracture. JAMA. 2006; 296:2947-53. https://pubmed.ncbi.nlm.nih.gov/17190895

41. Department of Health and Human Services (DHHS) Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents (Mar 29, 2012). From the US Department of Health and Human Services HIV/AIDS Information Services (AIDSinfo) website. http://www.aidsinfo.nih.gov/contentfiles/lvguidelines/glchunk/glchunk_32.pdf

42. Bristol-Myers Squibb. Reyataz (atazanavir sulfate) capsules prescribing information. Princeton, NJ; 2012 Mar.

43. Gilard M, Arnaud B, Cornily JC et al. Influence of omeprazole on the antiplatelet action of clopidogrel associated with aspirin. JACC. 2008; 51:256-60, doi:10.1016/j.jacc.2007.06.064. Accessed 2008 Dec 8. Available from website. http://content.onlinejacc.org/cgi/content/abstract/51/3/256 https://pubmed.ncbi.nlm.nih.gov/18206732

44. Pezalla E, Day D, Pulliadath I. Initial assessment of clinical impact of a drug interaction between clopidogrel and proton pump inhibitors. JACC. 2008; 52:1038-9. Letter. https://pubmed.ncbi.nlm.nih.gov/18786491

45. MEDCO. New study: A common class of GI medications reduce protection against heart attack in patients taking widely prescribed cardiovascular drug. Franklin Lakes, NJ; 2008 Nov 11. Press release from website. http://www.medco.com

46. Gilard M, Cornily JC, Boschat J. Initial assessment of clinical impact of a drug interaction between clopidogrel and proton pump inhibitors. JACC. 2008; 52:1039. Reply.

47. . PPI interactions with clopidogrel revisited. Med Lett Drugs Ther. 2009; 51:13-4.

48. Juurlink DN, Gomes T, Ko DT et al. A population-based study of the drug interaction between proton pump inhibitors and clopidogrel. CMAJ. 2009; 180:713-8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2659819/ https://pubmed.ncbi.nlm.nih.gov/19176635

49. Food and Drug Administration. Information on clopidogrel bisulfate (marketed as Plavix). Rockville, MD; 2010 Oct 27. From FDA website. http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm190836.htm

219. Gilard M, Arnaud B, Cornily JC et al. Influence of omeprazole on the antiplatelet action of clopidogrel associated with aspirin. JACC. 2008; 51:256-60, doi:10.1016/j.jacc.2007.06.064. Accessed 2008 Dec 8. Available from website. http://content.onlinejacc.org/cgi/content/abstract/51/3/256 https://pubmed.ncbi.nlm.nih.gov/18206732

220. Pezalla E, Day D, Pulliadath I. Initial assessment of clinical impact of a drug interaction between clopidogrel and proton pump inhibitors. JACC. 2008; 52:1038-9. Letter. https://pubmed.ncbi.nlm.nih.gov/18786491

221. MEDCO. New study: A common class of GI medications reduce protection against heart attack in patients taking widely prescribed cardiovascular drug. Franklin Lakes, NJ; 2008 Nov 11. Press release from website. http://www.medco.com

223. . PPI interactions with clopidogrel revisited. Med Lett Drugs Ther. 2009; 51:13-4.

224. Sanofi-Aventis/Bristol-Myers Squibb. Plavix, (clopidogrel bisulfate) tablets prescribing information. New York, NY; 2011 Dec.

225. Food and Drug Administration. Early communication about an ongoing safety review of clopidogrel bisulfate (marketed as Plavix). Rockville, MD; 2009 Jan 26. From FDA website. http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm079520.htm

226. Siller-Matula JM, Spiel AO, Lang IM et al. Effects of pantoprazole and esomeprazole on platelet inhibition by clopidogrel. Am Heart J. 2009; 157:148.e1-5.

227. Gilard M, Arnaud B, Le Gal G et al. Influence of omeprazole on the antiplatelet action of clopidogrel associated to aspirin. J Thromb Haemost. 2006; 4:2508-9. https://pubmed.ncbi.nlm.nih.gov/16898956

228. Anon. PPI interactions with clopidogrel. Med Lett Drugs Ther. 2009; 51:2-3.

229. Aubert RE, Epstein RS, Teagarden JR et al. Proton pump inhibitors effect on clopidogrel effectiveness: The clopidogrel Medco outcomes study. Circulation. 2008; 118:S_815, Abstract 3998.

230. Lau WC, Gurbel PA. The drug-drug interaction between proton pump inhibitors and clopidogrel. CMAJ. 2009; 180:699-700. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2659824/ https://pubmed.ncbi.nlm.nih.gov/19332744

232. Food and Drug Administration. Information for heathcare professionals: Update to the labeling of clopidogrel bisulfate (marketed as Plavix) to alert heathcare professionals about a drug interaction with omeprazole (marketed as Prilosec and Prilosec OTC). Rockville, MD; 2009 Nov 17. From FDA website. http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm190787.htm

233. Food and Drug Administration. Follow-up to the January 26, 2009 Early Communication about an ongoing safety review of clopidogrel bisulfate (marketed as Plavix) and omeprazole (marketed as Prilosec and Prilosec OTC). Rockville, MD; 2009 Nov 17. From FDA website. http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm190784.htm

234. Juurlink DN, Gomes T, Ko DT et al. A population-based study of the drug interaction between proton pump inhibitors and clopidogrel. CMAJ. 2009; 180:713-8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2659819/ https://pubmed.ncbi.nlm.nih.gov/19176635

235. Ho PM, Maddox TM, Wang L et al. Risk of adverse outcomes associated with concomitant use of clopidogrel and proton pump inhibitors following acute coronary syndrome. JAMA. 2009; 301:937-44. https://pubmed.ncbi.nlm.nih.gov/19258584

236. Norgard NB, Mathews KD, Wall GC. Drug-drug interaction between clopidogrel and the proton pump inhibitors. Ann Pharmacother. 2009; 43:1266-74. https://pubmed.ncbi.nlm.nih.gov/19470853

237. Last EJ, Sheehan AH. Review of recent evidence: potential interaction between clopidogrel and proton pump inhibitors. Am J Health Syst Pharm. 2009; 66:2117-22. https://pubmed.ncbi.nlm.nih.gov/19923312

238. Stanek EJ, Aubert RE, Flockhart DA et al. A national study of the effect of individual proton pump inhibitors on cardiovascular outcomes in patients treated with clopidogrel following coronary stenting: the Clopidogrel Medco Outcomes Study/displayItem.do?primaryKey=967345&type=ppt. Accessed 2009 Dec 15. https://www.theheart.org/displayItem.do?primaryKey=967345&

240. Stockl KM, Le L, Zakharyan A et al. Risk of rehospitalization for patients using clopidogrel with a proton pump inhibitor. Arch Intern Med. 2010; 170:704-10. https://pubmed.ncbi.nlm.nih.gov/20421557

243. Juurlink DN. Proton pump inhibitors and clopidogrel: putting the interaction in perspective. Circulation. 2009; 120:2310-2. https://pubmed.ncbi.nlm.nih.gov/19933929

248. Khalique SC, Cheng-Lai A. Drug interaction between clopidogrel and proton pump inhibitors. Cardiol Rev. 2009 Jul-Aug; 17:198-200.

250. Rude MK, Chey WD. Proton-pump inhibitors, clopidogrel, and cardiovascular adverse events: fact, fiction, or something in between?. Gastroenterology. 2009; 137:1168-71. https://pubmed.ncbi.nlm.nih.gov/19635603

300. Vestergaard P, Rejnmark L, Mosekilde L. Proton pump inhibitors, histamine H2 receptor antagonists, and other antacid medications and the risk of fracture. Calcif Tissue Int. 2006; 79:76-83. https://pubmed.ncbi.nlm.nih.gov/16927047

301. Corley DA, Kubo A, Zhao W et al. Proton pump inhibitors and histamine-2 receptor antagonists are associated with hip fractures among at-risk patients. Gastroenterology. 2010; 139:93-101. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2902649/ https://pubmed.ncbi.nlm.nih.gov/20353792

302. Yu EW, Blackwell T, Ensrud KE et al. Acid-suppressive medications and risk of bone loss and fracture in older adults. Calcif Tissue Int. 2008; 83:251-9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2596870/ https://pubmed.ncbi.nlm.nih.gov/18813868

303. Gray SL, LaCroix AZ, Larson J et al. Proton pump inhibitor use, hip fracture, and change in bone mineral density in postmenopausal women: results from the Women’s Health Initiative. Arch Intern Med. 2010; 170:765-71. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4240017/ https://pubmed.ncbi.nlm.nih.gov/20458083

304. Targownik LE, Lix LM, Metge CJ et al. Use of proton pump inhibitors and risk of osteoporosis-related fractures. CMAJ. 2008; 179:319-26. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2492962/ https://pubmed.ncbi.nlm.nih.gov/18695179

305. Food and Drug Administration. Possible increased risk of fractures of the hip, wrist, and spine with the use of proton pump inhibitors. May 25, 2010. From FDA web site. http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm213206.htm

307. Yang YX, Metz DC. Safety of proton pump inhibitor exposure. Gastroenterology. 2010; :.

308. Targownik LE, Lix LM, Leung S et al. Proton-pump inhibitor use is not associated with osteoporosis or accelerated bone mineral density loss. Gastroenterology. 2010; 138:896-904. https://pubmed.ncbi.nlm.nih.gov/19931262

310. Kaye JA, Jick H. Proton pump inhibitor use and risk of hip fractures in patients without major risk factors. Pharmacotherapy. 2008; 28:951-9. https://pubmed.ncbi.nlm.nih.gov/18657011

311. Abraham NS, Hlatky MA, Antman EM et al. ACCF/ACG/AHA 2010 Expert Consensus Document on the Concomitant Use of Proton Pump Inhibitors and Thienopyridines: A Focused Update of the ACCF/ACG/AHA 2008 Expert Consensus Document on Reducing the Gastrointestinal Risks of Antiplatelet Therapy and NSAID Use. A report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents. JACC. 2010; 56: Published online Nov 8, 2010.

317. Furlanetto TW, Faulhaber GA. Hypomagnesemia and Proton Pump Inhibitors: Below the Tip of the Iceberg. Arch Intern Med. 2011; :. https://pubmed.ncbi.nlm.nih.gov/21555654

318. Fernández-Fernández FJ, Sesma P, Caínzos-Romero T et al. Intermittent use of pantoprazole and famotidine in severe hypomagnesaemia due to omeprazole. Neth J Med. 2010; 68:329-30. https://pubmed.ncbi.nlm.nih.gov/21071783

319. Mackay JD, Bladon PT. Hypomagnesaemia due to proton-pump inhibitor therapy: a clinical case series. QJM. 2010; 103:387-95. https://pubmed.ncbi.nlm.nih.gov/20378675

320. Shabajee N, Lamb EJ, Sturgess I et al. Omeprazole and refractory hypomagnesaemia. BMJ. 2008; 337:a425. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2483862/ https://pubmed.ncbi.nlm.nih.gov/18617497

321. . In brief: PPI’s and hypomagnesemia. Med Lett Drugs Ther. 2011; 53:25.

322. Cundy T, Dissanayake A. Severe hypomagnesaemia in long-term users of proton-pump inhibitors. Clin Endocrinol (Oxf). 2008; 69:338-41. https://pubmed.ncbi.nlm.nih.gov/18221401

323. Broeren MA, Geerdink EA, Vader HL et al. Hypomagnesemia induced by several proton-pump inhibitors. Ann Intern Med. 2009; 151:755-6. https://pubmed.ncbi.nlm.nih.gov/19920278

324. Metz DC, Sostek MB, Ruszniewski P et al. Effects of esomeprazole on acid output in patients with Zollinger-Ellison syndrome or idiopathic gastric acid hypersecretion. Am J Gastroenterol. 2007; 102:2648-54. https://pubmed.ncbi.nlm.nih.gov/17764495

325. Kuipers MT, Thang HD, Arntzenius AB. Hypomagnesaemia due to use of proton pump inhibitors--a review. Neth J Med. 2009; 67:169-72. https://pubmed.ncbi.nlm.nih.gov/19581665

326. Epstein M, McGrath S, Law F. Proton-pump inhibitors and hypomagnesemic hypoparathyroidism. N Engl J Med. 2006; 355:1834-6. https://pubmed.ncbi.nlm.nih.gov/17065651

327. US Food and Drug Administration. FDA drug safety communication: Low magnesium levels can be associated with long-term use of proton pump inhibitor drugs (PPIs). Rockville, MD; 2011 March 2. From FDA website. http://www.fda.gov/Drugs/DrugSafety/ucm245011.htm

328. US Food and Drug Administration. Proton pump inhibitor drugs (PPIs): Drug safety communication- Low magnesium levels can be associated with long-term use. Rockville, MD; 2011 March 2. From FDA website. http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm245275.htm

329. Hoorn EJ, van der Hoek J, de Man RA et al. A case series of proton pump inhibitor-induced hypomagnesemia. Am J Kidney Dis. 2010; 56:112-6. https://pubmed.ncbi.nlm.nih.gov/20189276

330. Regolisti G, Cabassi A, Parenti E et al. Severe hypomagnesemia during long-term treatment with a proton pump inhibitor. Am J Kidney Dis. 2010; 56:168-74. https://pubmed.ncbi.nlm.nih.gov/20493607

331. GlaxoSmithKline. Lanoxin (digoxin) tablets prescribing information. Research Triangle Park, NC; 2009 Aug.

334. Horn JR, Hansten PD. Methotrexate and proton pump inhibitors. Pharm Times. 2012; 78(4). Published online 2012 Apr 9. http://www.pharmacytimes.com/publications/issue/2012/April2012/Methotrexate-and-Proton-Pump-Inhibitors

335. Food and Drug Administration. Drug safety communication: Clostridium difficile-associated diarrhea can be associated with stomach acid drugs known as proton pump inhibitors (PPIs). Rockville, MD; 2012 Feb 8. From FDA website. Accessed 2012 May 3l. http://www.fda.gov/Drugs/DrugSafety/ucm290510.htm

336. Cohen SH, Gerding DN, Johnson S et al. Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the society for healthcare epidemiology of America (SHEA) and the infectious diseases society of America (IDSA). Infect Control Hosp Epidemiol. 2010; 31:431-55. https://pubmed.ncbi.nlm.nih.gov/20307191

337. Shah S, Lewis A, Leopold D et al. Gastric acid suppression does not promote clostridial diarrhoea in the elderly. QJM. 2000; 93:175-81. https://pubmed.ncbi.nlm.nih.gov/10751237

338. Leonard AD, Ho KM, Flexman J. Proton pump inhibitors and diarrhoea related to Clostridium difficile infection in hospitalised patients: a case-control study. Intern Med J. 2012; 42:591-4. https://pubmed.ncbi.nlm.nih.gov/22616966

339. Kwok CS, Arthur AK, Anibueze CI et al. Risk of Clostridium difficile Infection With Acid Suppressing Drugs and Antibiotics: Meta-Analysis. Am J Gastroenterol. 2012; 107:1011-9. https://pubmed.ncbi.nlm.nih.gov/22525304

340. Dial S, Delaney JA, Barkun AN et al. Use of gastric acid-suppressive agents and the risk of community-acquired Clostridium difficile-associated disease. JAMA. 2005; 294:2989-95. https://pubmed.ncbi.nlm.nih.gov/16414946

341. Nerandzic MM, Pultz MJ, Donskey CJ. Examination of potential mechanisms to explain the association between proton pump inhibitors and Clostridium difficile infection. Antimicrob Agents Chemother. 2009; 53:4133-7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2764230/ https://pubmed.ncbi.nlm.nih.gov/19667292

343. Tibotec Therapeutics. Edurant (rilpivirine) tablets prescribing information. Raritan, NJ; 2011 May.

344. Abbott Laboratories. Kaletra (lopinavir/ritonavir) oral tablets and solution prescribing information. North Chicago, IL; 2012 May.

345. ViiV Healthcare. Lexiva (fosamprenavir calcium) tablets and oral suspension prescribing information. Research Triangle Park, NC; 2012 Apr.

346. Genentech USA. Invirase (saquinavir mesylate) capsules and tablets prescribing information. South San Francisco, CA; 2012 Feb.

348. Merck Sharp & Dohme. Isentress (raltegravir) film-coated tablets and chewable tablets prescribing information. Whitehouse Station, NJ; 2012 Apr.

350. Frelinger AL, Lee RD, Mulford DJ et al. A randomized, 2-period, crossover design study to assess the effects of dexlansoprazole, lansoprazole, esomeprazole, and omeprazole on the steady-state pharmacokinetics and pharmacodynamics of clopidogrel in healthy volunteers. J Am Coll Cardiol. 2012; 59:1304-11. https://pubmed.ncbi.nlm.nih.gov/22464259

351. Angiolillo DJ, Gibson CM, Cheng S et al. Differential effects of omeprazole and pantoprazole on the pharmacodynamics and pharmacokinetics of clopidogrel in healthy subjects: randomized, placebo-controlled, crossover comparison studies. Clin Pharmacol Ther. 2011; 89:65-74. https://pubmed.ncbi.nlm.nih.gov/20844485

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