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Gastrointestinal Safety of an Extended-Release, Nondeformable, Oral Dosage Form (OROS®)1

A Retrospective Study

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Abstract

Background: The OROS® osmotic (OSM) dosage form optimises extended-release oral administration by controlling the rate of drug release for a predetermined time, providing constant, patterned, or pulsed delivery profiles. OSM products include prescription medications for urology, CNS, and cardiovascular indications, as well as over-the-counter nasal/sinus congestion medications.

Methods: This retrospective study examines US gastrointestinal (GI) safety data for the OROS® dosage form following nearly two decades of use. Although GI injury and obstruction are known effects of oral medications, some reports have suggested that extended-release products pose a greater risk of GI injury and obstruction than other oral dosage forms. Products incorporating OROS® technology are being prescribed to an expanding range of patients; a review of the GI safety data for this dosage form thus seemed timely and appropriate. US safety information was obtained from three sources: (i) English language literature published from 1982 until June 1, 2000 from five major biomedical databases; (ii) postmarketing safety reports from January 1, 1983 until June 1, 2000 available through the Freedom of Information Act; and (iii) commercial safety information obtained directly from ALZA Corporation’s in-house safety database for those OSM products for which ALZA has reporting responsibility. US distribution data from IMS National Prescription Audit™ Plus data were used to estimate cumulative product distribution totals. These totals were combined with numbers of unique GI events to determine the estimated frequency of events.

Results: Nearly 13 billion OSM tablets are estimated to have been distributed in the US. The incidence of all clinically significant GI adverse events for OSM products (including intestinal, gastric, and oesophageal irritation, injury, and obstruction) reported in the US was approximately one case in >76 million tablets distributed. The majority (78%; estimated incidence: one case in 29 million tablets) of cases were reported in patients taking Procardia XL® (nifedipine). Oesophageal and lower GI obstruction were reported primarily in patients with pre-existing abnormalities or disease of the GI tract. Among paediatric patients, one obstruction was reported in an estimated 37.7 million tablets distributed. Reports of GI irritation associated with OSM products were consistent with known effects of the same drug substances in other dosage forms.

Conclusion: A review of long-term safety experience with products using OSM controlled-release technology yields a low incidence of clinically significant GI events. Properly prescribed, extended-release products provide substantial therapeutic and convenience benefits without additional risk.

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References

  1. Florence AT, Jani PU. Novel oral drug formulations, their potential in modulating adverse effects. Drug Saf 1994; 10(3): 233–66

    Article  PubMed  CAS  Google Scholar 

  2. Theeuwes F. Oral dosage form design: status and goals of oral osmotic systems technology. Pharm Int 1984; 5(12): 293–6

    CAS  Google Scholar 

  3. Theeuwes F. Evolution and design of ‘rate-controlled’ osmotic forms. Curr Med Res Opin 1983; 8(2): 20–7

    Article  PubMed  Google Scholar 

  4. Gatley MS. To be taken as directed. J R Coll Gen Pract 1968; 16: 39–44

    PubMed  CAS  Google Scholar 

  5. Kirsch M. Pill-induced esophageal obstruction: Discovery of a Peptic Stricture. South Med J 1997; 90(3): 861–2

    Article  PubMed  CAS  Google Scholar 

  6. Simko V, Joseph D, Michael S. Increased risk in esophageal obstruction with slow-release medications. J Assoc Acad Minor Phys 1997; 8(2): 38–42

    PubMed  CAS  Google Scholar 

  7. Schneider RP. Ischemic colitis caused by decongestant? Clin Gastroenterol 1995; 21(4): 335–6

    Article  CAS  Google Scholar 

  8. Shepherd MF. Bezoar formed by fragments of extended-release nifedipine tablets. Clin Pharm 1993; 12: 849–52

    PubMed  CAS  Google Scholar 

  9. Sporer KA, Manning JJ. Massive ingestion of sustained-release verapamil with a concretion and bowel infarction [case report]. Ann Emerg Med 1993; 22(3): 603–5

    Article  PubMed  CAS  Google Scholar 

  10. Wax PM. Intestinal infarction due to nifedipine overdose. Clin Toxicol 1995; 33(6): 725–8

    Article  CAS  Google Scholar 

  11. Smitz S, Bonnet V, Delporte JP, et al. Severe gastrointestinal dysfunction and retention of extended release nifedipine tablets. J Am Geriat Soc 1998; 46(5): 656–7

    PubMed  CAS  Google Scholar 

  12. Prisant LM, Carr AA, Bottini PB, et al. Nifedipine GITS (gastrointestinal therapeutic system) bezoar. Arch Intern Med 1991; 151: 1868–9

    Article  PubMed  CAS  Google Scholar 

  13. Hennessy S, Fogarty PM, Schulman KA, et al. Gastric obstruction with extended-release tablets [letter]. Ann Pharmacother 1991; 25: 678–9

    CAS  Google Scholar 

  14. Broussard R, Avots-Avotins A. Nondeformable nifedipine tablet occluding a previously compromised intestinal lumen [case report]. Am J Gastroenterol 1992; 87(9): 1312

    Google Scholar 

  15. Stack PE, Patel NR, Young MF, et al. Pharmacobezoars - the irony of the antidote: first case report of nifedipine XL bezoar. J Clin Gastroenterol 1994; 19(3): 264–71

    Article  PubMed  CAS  Google Scholar 

  16. Greenstein DB, Wilcox CM, Frontin K, et al. Nifedipine (Procardia XL) as a cause of false-positive results on barium enema study. South Med J 1994; 87(8): 808–10

    Article  PubMed  CAS  Google Scholar 

  17. Georgopoulos S, Gerdes H. Retention of nifedipine extended release tabs in a patient with a colonic stricture. Am J Gastroenterol 1995; 90(12): 2224–6

    PubMed  CAS  Google Scholar 

  18. Reid T, Rubins JB, Levine J, et al. Colonic medication bezoar from extended-release nifedipine and procainamide. Arch Fam Med 1995; 4: 715–7

    Article  PubMed  CAS  Google Scholar 

  19. Kwon HY, Scott RL, Mulloy JP. Small bowel Procardia XL tablet bezoar mimicking cystic pneumatosis intestinalis. Abdom Imaging 1996; 21: 142–4

    Article  PubMed  CAS  Google Scholar 

  20. Taylor JR, Streetman DS, Castle SS. Medication bezoars: a literature review and report of a case. Ann Pharmacother 1998; 32: 940–6

    Article  PubMed  CAS  Google Scholar 

  21. Niezabitowski LM, Nguyen BN, Gums JG. Extended release nifedipine bezoar identified one year after discontinuation. Ann Pharmacother 2000; 34: 862–4

    Article  PubMed  CAS  Google Scholar 

  22. Anderson RU, Mobley D, Blank B, et al. Once daily controlled versus immediate release oxybutynin chloride for urge urinary incontinence. J Urol 1999; 161: 1809–12

    Article  PubMed  CAS  Google Scholar 

  23. Blonde L, Guthrie RD, Tive L, et al. Glipizide GITS is effective and safe in a wide range of NIDDM patients: results of a double-blind placebo-controlled efficacy and safety trial. Diabetes 1996; 45(S2): P1054

    Google Scholar 

  24. Wagner MW, Markowitz JS, Patrick KS. Methylphenidate ER tablet lodging in esophagus. J Am Acad Child Adolesc Psychiatry 2001; 40: 1244–5

    Article  PubMed  CAS  Google Scholar 

  25. Swanson J, Greenhill L, Pelham W, et al. Initiating Concerta? (OROS® methylphenidate HCl) qd in children with attention-deficit/hyperactivity disorder. J Clin Res 2000; 3: 59–76

    Google Scholar 

  26. Greenhill LL. Evaluation of the efficacy and safety of Concerta (methylphenidate HCl) extended-release tablets, ritalin, and placebo in children with ADHD [abstract]. Neurology 2000; 54(7): A420–1

    Google Scholar 

  27. Wilens TE. Long-term safety and effectiveness of Concerta (methylphenidate HCl) in children with ADHD [abstract]. Neurology 2000; 54(7): A420

    Google Scholar 

  28. Wolraich ML. Evaluation of efficacy and safety of OROS® methylphenidate HCl (MPH) extended-release tablets, methylphenidate tid, and placebo in children with ADHD. Pediatr Res 2000; 47(4): 36A

    Google Scholar 

  29. Swanson JM, Wigal SB, Lerner MA. Comparison of the efficacy and safety of OROS® methylphenidate HCl with methylphenidate tid and placebo in children with ADHD [abstract]. Pediatr Res 2000; 47(4): 34A

    Google Scholar 

  30. Kernan WN, Viscoli CM, Brass LM, et al. Phenylpropanolamine and the risk of hemorrhagic stroke. N Engl J Med 2000; 343: 1826–32

    Article  PubMed  CAS  Google Scholar 

  31. Charatan F. Phenylpropanolamine in drugs could be a risk factor for stroke [news]. BMJ 2000 Oct 28; 321: 1037

    Article  PubMed  CAS  Google Scholar 

  32. Bem JL, Mann RD, Coulson R. Fatal gastrointestinal damage associated with the use of osmotic mini pump indomethacin (Osmosin). Pharmaceut Med 1988; 3: 35–43

    Google Scholar 

  33. Day TK. Intestinal perforation associated with osmotic slow release indomethacin capsules. BMJ 1983; 287: 1671–2

    Article  PubMed  CAS  Google Scholar 

  34. NSAIDs. Non-steroidal anti-inflammatory drugs: have we been spoilt for choice? Lancet 1984 Jan 21; I (8369): 141–2

  35. Laidler P, Maslin SC, Gilhome, et al. What’s new in Osmosin and intestinal perforation? Pathol Res Pract 1985; 180: 74–6

    Article  PubMed  CAS  Google Scholar 

  36. Cree IA, Walker MA, Wright M, et al. Osmosin and ileal ulceration: a case report. Scott Med J 1985; 30: 40–1

    PubMed  CAS  Google Scholar 

  37. Florence AT, Salole EG, Al-Dujaili H. Osmosin tablets [letter]. Pharm J 1984; 232(6269): 308

    Google Scholar 

  38. Bjarnason I, Hayllar J, MacPherson A, et al. Side effects of nonsteroidal anti-inflammatory drugs on the small and large intestine in humans. Gastroentrology 1993; 104: 1832–47

    CAS  Google Scholar 

  39. Swisher DA, Sendelbeck SL, Fara JW. Adherence of various oral dosage forms to the esophagus. Int J Pharm 1984; 22: 219–28

    Article  CAS  Google Scholar 

  40. Marvola M. Adherence of drug products to the oesophagus. Pharm Int 1982; 3: 294–6

    Google Scholar 

  41. CSM on NSAID ADRs in the elderly. Scrip 1986 Mar 7; 1084: 25

  42. Merck & Co. Inc. Press Release Jan 16, 1984

  43. Hothersall TE. Osmosin: implications for the arthritic patient: Clinical experience. Osmosin Press Briefing, 13 Jan, 1983

    Google Scholar 

  44. Inman WHW. Let’s get our act together. Side Effects of Drugs Annual 1985; 9: 15–23

    Article  Google Scholar 

  45. Calin A. Intestinal perforation associated with osmotic slow release Indomethacin capsules. BMJ 1984; 288: 240–1

    Article  PubMed  CAS  Google Scholar 

  46. Rhymer AR, Sromovsky JA, Dicenta C, et al. Osmosin: a multcentre evaluation of a technological advance in the treatment of osteoarthritis. Curr Med Res Opin 1983; 8(2): 62–71

    Article  PubMed  Google Scholar 

  47. Williams P, Williams P, Currie WJC, et al. A double-blind comparison of ‘Osmosin’, benoxaprofen and placebo in the treatment of osteoarthritis. Curr Med Res Opin 1983; 8(2): 90–8

    Article  PubMed  Google Scholar 

  48. Bobrove AM, Calin A. Efficacy and tolerance of a novel precision-dose formulation of indomethacin: double-blind trials in rheumatoid arthritis and osteoarthritis. Curr Med Res Opin 1983; 8(2): 55–61

    Article  PubMed  Google Scholar 

  49. Hart CB, Tempero KF, Sromovsky JA, et al. Osmosin (sodium indomethacin trihydrate) in the treatment of elderly patients with osteoarthritis. Curr Med Res Opin 1983; 8: 72–81

    Article  PubMed  Google Scholar 

  50. Griffin M. Epidemiology of nonsteroidal anti-inflammatory drug-associated gastrointestinal injury. Am J Med 1998; 104(3A): S23–9

    Article  Google Scholar 

  51. Roth SH. NSAID gastropathy. Arch Intern Med Aug 1996; 156: 1623–8

    Article  PubMed  CAS  Google Scholar 

  52. Lanza FL. Gastrointestinal toxicity of newer NSAIDs. Am J Gastroenterol 1993; 88: 1318–23

    PubMed  CAS  Google Scholar 

  53. Gabriel SE, Jaakkimainen L, Bombarier C. Risk for serious gastrointestinal complications related to use of nonsteroidal anti-inflammatory drugs: a meta-analysis. Ann Intern Med 1991; 115: 787–96

    PubMed  CAS  Google Scholar 

  54. Non-steroidal anti-inflammatory drugs and serious gastrointestinal adverse reactions — 2. BMJ 1986 May 3; 292: 1190–1

  55. Cohen P. Non-steroidal anti-inflammatory drugs and serious gastrointestinal adverse reactions - 1 [letter]. BMJ 1986; 292: 614

    Article  Google Scholar 

  56. Lanza F, Nelson R, Greenberg B. Effects of fenbufen, indomethacin, naproxen, and placebo on gastric mucosa of normal volunteers. A comparative endoscopic and photographic evaluation. Am J Med 1983: 75–9

    Google Scholar 

  57. O’Brien W. Pharmacology of nonsteroidal anti-inflammatory drugs, practical review for clinicians. Am J Med 1983 Oct 31; 75(4B): 32–9

    Article  PubMed  Google Scholar 

  58. Coutrot S, Roland D, Barbier J, et al. Acute perforation of colonic diverticula associated with short-term indomethacin. Lancet 1978; II: 1055–6

    Article  Google Scholar 

  59. Sturges HF, Krone CL. Ulceration and stricture of the jejunum in a patient on long-term indomethacin therapy. Am J Gastroenterol 1973; 59: 162–9

    PubMed  CAS  Google Scholar 

  60. Shack ME. Drug induced ulceration and perforation of the small intestine. Ariz Med 1966 Jul; 23(7): 517–23

    PubMed  CAS  Google Scholar 

  61. Puspok A, Kiener HP, Oberhuber G. Clinical, endoscopic and histologic spectrum of nonsteroidal anti-inflammatory drug-induced lesions in the colon. Dis Colon Rectum 2000; 43(5): 685–91

    Article  PubMed  CAS  Google Scholar 

  62. McGettigan P, Henry D. Current problems with non-specific COX inhibitors. Curr Pharm Des 2000; 6(17): 1693–724

    Article  PubMed  CAS  Google Scholar 

  63. Gut A, Halter F, Ruchit C. Non-steroidal anti-inflammatory drugs and acetylsalicylic acid: side effects distal to the duodenum. Schweiz Med Wochenschr 1996; 126(15): 616–25

    PubMed  CAS  Google Scholar 

  64. Bellamy N, Bensen W, Beaulieu A, et al. A multicenter study of nabumetone and diclofenac SR in patients with osteoarthritis. J Rheumatol 1995; 22(5): 915–20

    PubMed  CAS  Google Scholar 

  65. Schönberger B, Nickl S, Schweiger F. Colonic ulcerations associated with diclofenac treatment. Can J Gastroenterol 1992; 6(1): 15–7

    Google Scholar 

  66. Kehrer G, Bosseckert H, Koppe P, et al. Unusual negative side effects of non-steroidal anti-inflammatory drugs in the proximal colon. Z Gastroenterol 2000 Jun; 38(6): 499–503

    Article  PubMed  CAS  Google Scholar 

  67. Aabakken L. Small bowel side-effects of non-steroidal antiinflammatory drugs. J Gastroenterol Hepatol 1999; 11(4): 383–8

    Article  CAS  Google Scholar 

  68. Robinson M, Wheatley T, Leach I. Nonsteroidal anti-inflammatory drug-induced colonic stricture. An unusual cause of large bowel obstruction and perforation. Dig Dis Sci 1995; 40(2): 315–9

    Article  PubMed  CAS  Google Scholar 

  69. Davies NM. Toxicity of nonsteroidal anti-inflammatory drugs in the large intestine. Dis Colon Rectum 1995; 38(12): 1311–21

    Article  PubMed  CAS  Google Scholar 

  70. Halter F, Weber B, Huber T, et al. Diaphragm disease of the ascending colon. Association with sustained-release diclofenac. J Clin Gastroenterol 1993; 16(1): 74–80

    Article  PubMed  CAS  Google Scholar 

  71. Lang J, Price AB, Levi AJ, et al. Diaphragm disease: pathology of disease of the small intestine induced by non-steroidal anti-inflammatory drugs. J Clin Pathol 1988; 41: 516–26

    Article  PubMed  CAS  Google Scholar 

  72. Madhok R, MacKenzie JA, Lee FD, et al. Small bowel ulceration in patients receiving non-steroidal anti-inflammatory drugs for rheumatoid arthritis. Q J Med 1986; NS58(225): 53–8

    Google Scholar 

  73. Langman MJS, Morgan L, Worrall A. Use of anti-inflammatory drugs by patients admitted with small or large bowel perforations and haemorrhage. BMJ 1985; 290: 347–9

    Article  PubMed  CAS  Google Scholar 

  74. Boyce Jr HW. Drug-induced esophageal damage: diseases of medical progress. Gastrointest Endosc 1998; 47(6): 547–50

    Article  PubMed  Google Scholar 

  75. Uchegbu IF, Florence AT. Adverse drug events related to dosage forms and delivery systems. Drug Saf 1996; 14(1): 39–67

    Article  PubMed  CAS  Google Scholar 

  76. Kikendall JW. Pill esophagitis. J Clin Gastroenterol 1999; 28(4): 298–305

    Article  PubMed  CAS  Google Scholar 

  77. McCord GS, Clouse RE. Pill-induced esophageal structures: clinical features and risk factors for development. Am J Med 1990; 88: 512–8

    Article  PubMed  CAS  Google Scholar 

  78. Maroy B. Esophageal ulcer after ingestion of tetracycline capsules [Ulcere oesophagien apres prise de tetracycline capsules]. Ann Radiol (Paris) 1985; 28(5): 399–400

    CAS  Google Scholar 

  79. Carlborg B, Farmer JC. Esophageal corrosion tests with doxycycline monohydrate tablets. Curr Ther Res Clin Exp 1983; 34: 110–6

    Google Scholar 

  80. Geschwind A. Oesophagitis and oesophageal ulceration following ingestion of doxycycline tablets. Med J Aust 1984; 140: 223

    PubMed  CAS  Google Scholar 

  81. Davies NM. Sustained release and enteric coated NSAIDs: are they really GI safe? J Pharm Pharm Sci 1999; 2(1): 5–14

    PubMed  CAS  Google Scholar 

  82. Aabakken L, Bjornbeth BA, Hofstad B, et al. Comparison of the gastrointestinal side effects of naproxen formulated as plain tablets, enteric-coated tablets, or enteric-coated granules in capsules. Scand J Gastroenterol 1989; 163: 65–73

    Article  CAS  Google Scholar 

  83. Bjorkman D. Nonsteroidal anti-inflammatory drug-associated toxicity of the liver, lower gastrointestinal tract and esophagus. Am J Med 1998; 105(5A): S17–21

    Article  Google Scholar 

  84. Evans KT, Roberts GM. Where do all the tablets go? Lancet 1976 Dec 4; 2(7997): 1237–9

    Article  PubMed  CAS  Google Scholar 

  85. Witteman B, Weterman I, Griffioen G, et al. Intestinal obstruction due to non-soluble tablets and Budd-Chiari syndrome in a female with Crohn’s disease. Ned Tijdschr Geneeskd 1991; 135(17): 766–9

    PubMed  CAS  Google Scholar 

  86. O’Malley JAM, Ferrucci JT, Goodgame Jr JT. Medication bezoar: intestinal obstruction by an isocal bezoar. Gastrointest Radiol 1981; 6: 141–4

    Article  PubMed  Google Scholar 

  87. Lebenthal E. High strength pancreatic exocrine enzyme capsules associated with colonic strictures in patients with cystic fibrosis: ‘more is not necessarily better.’ J Pediatr Gastroenterol Nutr 1994; 18: 423–5

    Article  PubMed  CAS  Google Scholar 

  88. Bronson D, Gamelli R. Jejunal ulceration and stricture due to wax-matrix potassium chloride tablets and amitriptyline. J Clin Pharmacol 1987; 27(10): 788–9

    PubMed  CAS  Google Scholar 

  89. Shaffer JL, Higham C, Turnber LA. Hazards of slow-release preparations in patients with bowel strictures [abstract]. Lancet 1980; Aug 30 1980; 2(8192): 487

    Article  CAS  Google Scholar 

  90. Vickery R. Unusual complication of excessive ingestion of vitamin C tablets. Int Surg 1973; 58(6): 422–3

    PubMed  CAS  Google Scholar 

  91. Potyk D. Intestinal obstruction from impacted antacid tablets. N Engl J Med 1970; 283(3): 134–5

    Article  PubMed  CAS  Google Scholar 

  92. Lewis JH. Esophageal and small bowel obstruction from Guar Gum-containing ‘diet pills’: analysis of 26 cases reported to the Food and Drug Administration. Am J Gastroenterol 1992; 87(10): 1424–8

    PubMed  CAS  Google Scholar 

  93. Nightingale SL. Distribution of Cal-Ban diet pills halted [letter]. JAMA 1990; 264(14): 1802

    Article  PubMed  CAS  Google Scholar 

  94. Farinas E, Hong P. Upper gastrointestinal obstruction associated with Claritin-D 24 hour extended release tablets. J Allergy Clin Immunol 1997; 100(3): 427–8

    Article  PubMed  CAS  Google Scholar 

  95. Ransom JH. Esophageal retention of loratadine plus pseudoephedrine extended-release tablets (Claritin-D 24 hour). J Allergy Clin Immunol 1998; 101(2): 287–8

    Article  PubMed  CAS  Google Scholar 

  96. Schering Plough. Dear Doctor letter concerning Claritin-D 24 hour [online]. Available from URL: http://www.fda.gov/medwatch/safety/1998/clarit.htm [Accessed 1998 Dec 7]

  97. Wilson CG, Hardy JG, Davis SS. Sticking of dosage forms in the gastrointestinal tract [letter]. Gut 1986; 27(2): 26

    Article  Google Scholar 

  98. Fisher R, Malmud L, Applegate G, et al. Effect of bolus compositon on esophageal transit: concise communication. J Nucl Med 1982; 23: 878–82

    PubMed  CAS  Google Scholar 

  99. Stack PE, Thomas E. Pharmacobezoar: an evolving new entity. Dig Dis 1995; 13: 356–64

    Article  PubMed  CAS  Google Scholar 

  100. Drug bezoars. Prescrire Int 1999 Feb; 8 (39): 20–1

  101. White MV, Sander N. Asthma from the perspective of the patient. J Allergy Clin Immunol 1999; 104(2): S47–52

    Article  PubMed  CAS  Google Scholar 

  102. Frishman WH, Glasser S, Stone P, et al. Comparison of controlled-onset, extended-release verapamil with amlodipine and amlodipine plus atenolol on exercise performance and ambulatory ischemia in patients with chronic stable angina pectoris. Am J Cardiol 1999; 83(4): 507–14

    Article  PubMed  CAS  Google Scholar 

  103. Testa MA, Simonson DC. Health economic benefits and quality of life during improved glycemic control in patients with type 2 diabetes mellitus: a randomized controlled, double-blind trial. JAMA 1998; 280(17): 1490–6

    Article  PubMed  CAS  Google Scholar 

  104. Simonson DC, Kourides IA, Feingolos M, et al. Efficacy, safety, and dose-response characteristics of glipizide gastrointestinal therapeutic system on glycemic control and insulin secretion in NIDDM. Diabetes Care 1997; 20(4): 597–606

    Article  PubMed  CAS  Google Scholar 

  105. Martin RJ, Kraft M, Beaucher WN, et al. Comparative study of extended-release albuterol sulfate and long-acting inhaled salmeterol xinafoate in the treatment of nocturnal asthma. Ann Allergy Asthma Immunol 1999; 83(2): 121–6

    Article  PubMed  CAS  Google Scholar 

  106. Toal CB, Motro M, Baird MG, et al. Effectiveness of nifedipine GITS in combination with atenolol in chronic stable angina. Can J Cardiol 1999; 15(10): 1103–9

    PubMed  CAS  Google Scholar 

  107. Testa MA, Turner RR, Simonson DC, et al. Quality of life and calcium channel blockade with nifedipine GITS versus amlodipine in hypertensive patients in Spain. J Hypertens 1998; 16(12 Pt 1): 1839–47

    Article  PubMed  CAS  Google Scholar 

  108. Hall WD, Reed JW, Flack JM, et al. Comparison of the efficacy of dihydropyridine calcium channel blockers in African American patients with hypertension. Arch Int Med 1998; 158(18): 2029–34

    Article  CAS  Google Scholar 

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Acknowledgements

This review was funded by ALZA Corporation.

The authors would like to acknowledge the valuable contributions of Paula Elster, Karen Morse, and Kristen Mayo.

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  1. Department of Pediatrics, Stanford University, Stanford, 94305, USA

    Dorsey M. Bass

  2. ALZA Corporation, Mountain View, California, USA

    Mary Prevo & Deborah S. Waxman

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Bass, D.M., Prevo, M. & Waxman, D.S. Gastrointestinal Safety of an Extended-Release, Nondeformable, Oral Dosage Form (OROS®)1 . Drug-Safety 25, 1021–1033 (2002). https://doi.org/10.2165/00002018-200225140-00004

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