Class: Proton-pump Inhibitors
Chemical Name: 2-[(R)-[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridinyl]methyl]sulfinyl]-1H-benzimidazole
Molecular Formula: C16H14F3N3O2S
CAS Number: 138530-94-6
Brands: Dexilant (formerly Kapidex)
Uses for Dexlansoprazole
Gastroesophageal Reflux (GERD)
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†, including esophageal, gastroduodenal, and jejunoileal disease.14 15 16 17 18 19 20
Dexlansoprazole Dosage and Administration
Administer orally once daily.1
Administer without regard to food; however, if symptoms after a meal do not respond adequately to postprandial administration, consider preprandial administration (because the effect on gastric pH during the initial 4 hours after a dose may be decreased slightly when dexlansoprazole is taken after a meal).1 13
Swallow capsules whole; alternatively, open capsule and sprinkle contents on a tablespoonful of applesauce and swallow immediately without chewing.1
Chronic, lifelong therapy with a proton-pump inhibitor is appropriate for many GERD patients.6
Treatment of Erosive EsophagitisOral
60 mg once daily for up to 8 weeks.1
Maintenance of Healing of Erosive EsophagitisOral
GERD without Erosive EsophagitisOral
30 mg once daily for 4 weeks.1
No dosage adjustment necessary in mild hepatic impairment (Child-Pugh class A).1 Consider maximum dosage of 30 mg daily in moderate hepatic impairment (Child-Pugh class B).1 Not studied in severe hepatic impairment (Child-Pugh class C).1
No dosage adjustment necessary.1
No dosage adjustment necessary.1
Cautions for Dexlansoprazole
Known hypersensitivity to dexlansoprazole or any ingredient in the formulation.1
Hypersensitivity reactions (e.g., anaphylaxis, toxic epidermal necrolysis, Stevens-Johnson syndrome) reported.1
Response to dexlansoprazole therapy 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
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 9 300 301 302 303 304 305 Magnitude of risk is unclear;9 300 301 302 303 304 305 310 causality not established.305 FDA is continuing to evaluate this safety concern.305
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 9 303 305 307
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 dexlansoprazole.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
Possible Prescribing and Dispensing Errors
Ensure accuracy of prescription; similarity in spelling of Kapidex (former trade name for dexlansoprazole) and Casodex (trade name for bicalutamide, a nonsteroidal antiandrogenic antineoplastic agent220 ) or Kadian (a trade name for morphine sulfate, an opiate agonist analgesic221 ) may result in errors.217 218 219 223 In April 2010, manufacturer changed trade name for dexlansoprazole from Kapidex to Dexilant to avoid future errors.1 217
Also be aware of potential for Kapidex to be confused with Capadex (fixed-combination propoxyphene/acetaminophen preparation that is available via the Internet and is marketed in certain other countries [e.g., Australia]).216 219
Safety and efficacy not established in children <18 years of age.1
No substantial differences in safety and efficacy relative to younger adults, but increased sensitivity of some older patients cannot be ruled out.1
Systemic exposure to dexlansoprazole is increased approximately twofold in individuals with moderate hepatic impairment.1 Not studied in severe hepatic impairment.1 (See Hepatic Impairment under Dosage and Administration.)
Common Adverse Effects
Interactions for Dexlansoprazole
Metabolized by CYP2C19 and CYP3A4.1
Unlikely to inhibit CYP isoenzymes 1A1, 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, or 3A4.1
Drugs Metabolized by Hepatic Microsomal Enzymes
Substrates of CYP isoenzymes 1A1, 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, or 3A: Pharmacokinetic interaction unlikely.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.)
Manufacturer of dexlansoprazole 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);11 administer the proton-pump inhibitor approximately 12 hours before ritonavir-boosted atazanavir10 11
Certain CYP2C19 inhibitors (e.g., omeprazole, esomeprazole) reduce exposure to clopidogrel’s active metabolite and decrease platelet inhibitory effect; potentially may reduce clopidogrel’s clinical efficacy30 31 40 41 42 224 225 228 229 230 235 236 237 238 240 311
Manufacturer of dexlansoprazole states clopidogrel dosage adjustment not required if used with recommended dexlansoprazole dosages1
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;30 31 46 224 230 350 alternatively, consider using a histamine H2-receptor antagonist (ranitidine, famotidine, nizatidine)30 31 230 but not cimetidine (also a potent CYP2C19 inhibitor)232 233
See table entry for gastric pH-dependent drugs
Diuretics (i.e., loop or thiazide diuretics)
Possible increased risk of hypomagnesemia327
Use of esomeprazole with fosamprenavir (with or without ritonavir) did not substantially affect concentrations of amprenavir (active metabolite of fosamprenavir)345
Gastric pH-dependent drugs (e.g., ampicillin esters, digoxin, iron salts, ketoconazole)
Dexlansoprazole may alter drug absorption1
No dosage adjustment required when proton-pump inhibitors used with lopinavir/ritonavir10
Manufacturer of dexlansoprazole 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 inhibitor333 334
Possible increase in whole blood tacrolimus concentrations, particularly in transplant patients with intermediate or poor metabolizer phenotypes for CYPC191
No change in warfarin pharmacokinetics or INR observed in healthy individuals given warfarin 25 mg on day 6 of an 11-day course of dexlansoprazole 90 mg once daily;1 12 however, increased PT and INR reported in patients receiving warfarin concomitantly with proton-pump inhibitors1
May need to monitor PT and INR1
Commercially available capsules contain 2 types of enteric-coated granules that dissolve at different pH values.1 Following oral administration, an initial (smaller) peak plasma concentration occurs at 1–2 hours followed by a second (larger) peak concentration at 4–5 hours.1 25
Following once-daily administration for 5 days, gastric pH is >4 for 17 hours per day with dexlansoprazole 60 mg versus 14 hours per day with lansoprazole 30 mg.1
Administration in fed versus fasted state not associated with significant difference in mean gastric pH; however, effect on gastric pH during initial 4 hours after a dose may be decreased slightly when dexlansoprazole is taken after a meal.1 13 (See Oral Administration under Dosage and Administration.)
Plasma Protein Binding
Major circulating metabolite varies depending on CYP2C19 phenotype, but dexlansoprazole is the major circulating form of the drug regardless of CYP2C19 phenotype.1
Eliminated in urine (51%) and feces (48%); unchanged drug is not recovered in urine.1
Approximately 1–2 hours.1
Intermediate or poor metabolizers of CYP2C19 substrates: Systemic exposure to dexlansoprazole generally is increased.1 In Japanese men, AUC increased twofold in intermediate metabolizers and up to 12-fold in poor metabolizers compared with extensive metabolizers.1
Moderate hepatic impairment: Twofold increase in AUC.1
Renal impairment: Pharmacokinetic alterations not expected.1
Geriatric individuals: Half-life of 2.2 hours (versus 1.5 hours in younger individuals); not considered clinically important.1
25°C (may be exposed to 15–30°C).1
For information on systemic interactions resulting from concomitant use, see Interactions.
Immediately use extemporaneous mixtures of capsule contents and applesauce.1
Dexlansoprazole is the R-isomer of lansoprazole (a racemic mixture of R- and S-isomers).1 5 22 Both isomers inhibit hydrogen-potassium ATPase, but plasma clearance of dexlansoprazole is slower than that of S-lansoprazole.25 32
Proton-pump inhibitors inhibit basal and stimulated gastric acid secretion.24
Dexlansoprazole binds to and inactivates hydrogen-potassium ATPase (proton, hydrogen, or acid pump) in gastric parietal cells, blocking the final step in secretion of hydrochloric acid; results in potent, long-lasting inhibition of gastric acid secretion.1 22
Advice to Patients
Importance of swallowing capsule whole or, alternatively, of opening capsule and sprinkling contents on a tablespoonful of applesauce and swallowing immediately without chewing.1 Dexlansoprazole may be administered without regard to food (see Oral Administration under Dosage and Administration).1
Importance of continuing therapy for the entire treatment course, unless directed otherwise.1
Risk of hypomagnesemia; importance of immediately reporting and seeking care for any cardiovascular or neurologic manifestations (e.g., palpitations, dizziness, seizures, tetany).1
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and herbal supplements, as well as any concomitant illnesses.1
Possible increased risk of Clostridium difficile infection; importance of contacting a clinician if persistent watery stools, abdominal pain, and fever occur.335
Importance of informing clinicians of any symptoms suggestive of an allergic reaction (e.g., facial swelling, rash).1
Importance of women informing their clinicians if they are or plan to become pregnant or plan to breast-feed.1
Importance of informing patients of other important precautionary information.1 (See Cautions.)
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.
Capsules, delayed-release (containing enteric-coated granules)
AHFS DI Essentials. © Copyright, 2016, American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.
Date published: February 01, 2010
Last reviewed: February 04, 2013
Date modified: February 08, 2016
1. Takeda Pharmaceuticals America, Inc. Dexilant (dexlansoprazole) delayed-release capsules prescribing information. Deerfield, IL; 2012 May.
2. Sharma P, Shaheen NJ, Perez MC et al. Clinical trials: healing of erosive oesophagitis with dexlansoprazole MR, a proton pump inhibitor with a novel dual delayed-release formulation--results from two randomized controlled studies. Aliment Pharmacol Ther. 2009; 29:731-41. [PubMed 19183157]
3. Fass R, Chey WD, Zakko SF et al. Clinical trial: the effects of the proton pump inhibitor dexlansoprazole MR on daytime and nighttime heartburn in patients with nonerosive reflux disease. Aliment Pharmacol Ther. 2009; :. [PubMed 19392864]
4. Metz DC, Howden CW, Perez MC et al. Clinical trial: dexlansoprazole MR, a proton pump inhibitor with dual delayed-release technology, effectively controls symptoms and prevents relapse in patients with healed erosive oesophagitis. Aliment Pharmacol Ther. 2009; 29:742-54. [PubMed 19210298]
5. . Dexlansoprazole (Kapidex) for GERD and erosive esophagitis. Med Lett Drugs Ther. 2009; 51:21-2. [PubMed 19305367]
6. 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. 2005; 100:190-200. [PubMed 15654800]
7. 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.
8. Gregor JC. Acid suppression and pneumonia.; a clinical indication for rational prescibing. JAMA. 2004;292:2012-3. Editorial.
9. 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. [PubMed 17190895]
10. 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.
11. Bristol-Myers Squibb. Reyataz (atazanavir sulfate) capsules prescribing information. Princeton, NJ; 2012 Mar.
12. Vakily M, Lee RD, Wu J et al. Drug interaction studies with dexlansoprazole modified release (TAK-390MR), a proton pump inhibitor with a dual delayed-release formulation: results of four randomized, double-blind, crossover, placebo-controlled, single-centre studies. Clin Drug Investig. 2009; 29:35-50. [PubMed 19067473]
13. Lee RD, Vakily M, Mulford D et al. Clinical trial: the effect and timing of food on the pharmacokinetics and pharmacodynamics of dexlansoprazole MR, a novel Dual Delayed Release formulation of a proton pump inhibitor--evidence for dosing flexibility. Aliment Pharmacol Ther. 2009; 29:824-33. [PubMed 19243357]
14. 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. [IDIS 461432] [PubMed 11280528]
15. Valori RM, Cockel R. Omeprazole for duodenal ulceration in Crohn’s disease. Br Med J. 1990; 300:438-9.
16. Bianchi G, Ardizzone S, Petrillo M et al. Omeprazole for peptic ulcer in Crohn’s disease. Am J Gastroenterol. 1991; 86: 245-6. [PubMed 1992643]
17. Przemioslo RT, Mee AS. Omeprazole in possible esophageal Crohn’s disease. Dig Dis Sci. 1994; 39:1594-5. [IDIS 333053] [PubMed 8026276]
18. Dickinson JB. Is omeprazole helpful in inflammatory bowel disease? J Clin Gastroenterol. 1994; 18:317-9.
19. 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.
20. Freston JW. Review article: role of proton pump inhibitors in non-H. pylori-related ulcers. Aliment Pharmacol Ther. 2001; 15(Suppl 2):2-5. [PubMed 11556873]
21. Takeda Pharmaceuticals America, Inc. Prevacid (lansoprazole) delayed-release capsules, for delayed-release oral suspension, and delayed-release orally disintegrating tablets prescribing information. Deerfield, IL; 2008 Nov.
22. Welage LS. Pharmacologic properties of proton pump inhibitors. Pharmacotherapy. 2003; 23:74S-80S. [PubMed 14587961]
23. Zhang W, Wu J, Atkinson SN. Effects of dexlansoprazole MR, a novel dual delayed release formulation of a proton pump inhibitor, on plasma gastrin levels in healthy subjects. J Clin Pharmacol. 2009; 49:444-54. [PubMed 19318694]
24. AstraZeneca. Prilosec (omeprazole) delayed-release capsules and (omeprazole magnesium) for delayed-release oral suspension prescribing information. Wilmington, DE; 2008 Mar.
25. Vakily M, Zhang W, Wu J et al. Pharmacokinetics and pharmacodynamics of a known active PPI with a novel Dual Delayed Release technology, dexlansoprazole MR: a combined analysis of randomized controlled clinical trials *. Curr Med Res Opin. 2009; 25:627-38. [PubMed 19232037]
26. 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. [PubMed 18206732]
27. 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. [PubMed 18786491]
28. 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.
29. 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.
30. . PPI interactions with clopidogrel revisited. Med Lett Drugs Ther. 2009; 51:13-4.
31. 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. [PubMed 19176635]
32. Miura M, Tada H, Yasui-Furukori N et al. Pharmacokinetic differences between the enantiomers of lansoprazole and its metabolite, 5-hydroxylansoprazole, in relation to CYP2C19 genotypes. Eur J Clin Pharmacol. 2004; 60:623-8. [PubMed 15448955]
40. 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. [PubMed 18206732]
41. 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. [PubMed 18786491]
42. 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.
44. . PPI interactions with clopidogrel revisited. Med Lett Drugs Ther. 2009; 51:13-4.
45. 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. [PubMed 19176635]
46. Food and Drug Administration. Information on clopidogrel bisulfate (marketed as Plavix). Rockville, MD; 2010 Oct 27. From FDA website.
216. Institute for Safe Medication Practices. Kapidex or Capadex? ISMP Medication Safety Alert! Community/Ambulatory Care edition. Horsham, PA; 2009 Aug. From ISMP website.
217. US Food and Drug Administration. FDA approves name change for heartburn drug Kapidex. Rockville, MD; 2010 Mar 4. News release from FDA website.
218. Institute for Safe Medication Practices. Kapidex-Casodex confusion. ISMP Medication Safety Alert! Community/Ambulatory Care edition. Horsham, PA; 2009 Jul. From ISMP website.
219. Institute for Safe Medication Practices. ISMP quarterly action agenda July–September 2009. ISMP Medication Safety Alert! Acute Care edition. Horsham, PA; 2009 Oct 8. From ISMP website.
220. AstraZeneca Pharmaceuticals. Casodex (bicalutamide) tablets prescribing information. Wilnington, DE; 2008.
221. Actavis Kadian. Kadian (morphine sulfate) extended-release capsules prescribing information. Morristown, NJ; 2009 Feb.
223. Institute for Safe Medication Practices. Progress with preventing name confusion errors. ISMP Medication Safety Alert! Acute Care edition. Horsham, PA; 2007 Aug 9. From ISMP website.
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.
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. [PubMed 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. [PubMed 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.
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.
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. [PubMed 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. [PubMed 19258584]
236. Norgard NB, Mathews KD, Wall GC. Drug-drug interaction between clopidogrel and the proton pump inhibitors. Ann Pharmacother. 2009; 43:1266-74. [PubMed 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. [PubMed 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. Available from website. Accessed 2009 Dec 15.
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. [PubMed 20421557]
243. Juurlink DN. Proton pump inhibitors and clopidogrel: putting the interaction in perspective. Circulation. 2009; 120:2310-2. [PubMed 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. [PubMed 19635603]
251. 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. [PubMed 18206732]
252. 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. [PubMed 18786491]
253. 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.
254. . PPI interactions with clopidogrel revisited. Med Lett Drugs Ther. 2009; 51:13-4.
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. [PubMed 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. [PubMed 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. [PubMed 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. [PubMed 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. [PubMed 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.
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. [PubMed 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. [PubMed 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.
312. 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. [PubMed 19923312]
313. 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. [PubMed 20421557]
314. Juurlink DN. Proton pump inhibitors and clopidogrel: putting the interaction in perspective. Circulation. 2009; 120:2310-2. [PubMed 19933929]
315. Khalique SC, Cheng-Lai A. Drug interaction between clopidogrel and proton pump inhibitors. Cardiol Rev. 2009 Jul-Aug; 17:198-200.
316. Rude MK, Chey WD. Proton-pump inhibitors, clopidogrel, and cardiovascular adverse events: fact, fiction, or something in between?. Gastroenterology. 2009; 137:1168-71. [PubMed 19635603]
317. Furlanetto TW, Faulhaber GA. Hypomagnesemia and Proton Pump Inhibitors: Below the Tip of the Iceberg. Arch Intern Med. 2011; :. [PubMed 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. [PubMed 21071783]
319. Mackay JD, Bladon PT. Hypomagnesaemia due to proton-pump inhibitor therapy: a clinical case series. QJM. 2010; 103:387-95. [PubMed 20378675]
320. Shabajee N, Lamb EJ, Sturgess I et al. Omeprazole and refractory hypomagnesaemia. BMJ. 2008; 337:a425. [PubMed 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. [PubMed 18221401]
323. Broeren MA, Geerdink EA, Vader HL et al. Hypomagnesemia induced by several proton-pump inhibitors. Ann Intern Med. 2009; 151:755-6. [PubMed 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. [PubMed 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. [PubMed 19581665]
326. Epstein M, McGrath S, Law F. Proton-pump inhibitors and hypomagnesemic hypoparathyroidism. N Engl J Med. 2006; 355:1834-6. [PubMed 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.
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.
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. [PubMed 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. [PubMed 20493607]
331. GlaxoSmithKline. Lanoxin (digoxin) tablets prescribing information. Research Triangle Park, NC; 2009 Aug.
333. Bezabeh S, Mackey AC, Kluetz P et al. Accumulating evidence for a drug-drug interaction between methotrexate and proton pump inhibitors. Oncologist. 2012; 17:550-4. [PubMed 22477728]
334. Horn JR, Hansten PD. Methotrexate and proton pump inhibitors. Pharm Times. 2012; 78(4). Published online 2012 Apr 9.
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.
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. [PubMed 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. [PubMed 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. [PubMed 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. [PubMed 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. [PubMed 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. [PubMed 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. [PubMed 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. [PubMed 20844485]