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Drug-Induced Oesophageal Disorders

Pathogenesis, Incidence, Prevention and Management

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Abstract

Drug-induced injury of the oesophagus is a common cause of oesophageal complaints. ‘Pill-induced’oesophagitis is associated with the ingestion of certain drugs and accounts for many cases of erosive oesophagitis. To date, more than 70 drugs have been reported to induce oesophageal disorders. Antibacterials such as doxycycline, tetracycline and clindamycin are the offending agents in more than 50% of cases. Other commonly prescribed drugs that cause oesophageal injury include aspirin (acetylsalicylic acid), potassium chloride, ferrous sulfate, quinidine, alprenolol and various steroidal and nonsteroidal anti-inflammatory agents. However, many physicians and even more patients are not aware of this problem.

Capsules or tablets are commonly delayed in their passage through the oesophagus. Highly caustic coatings, direct medication injury and poor oesophageal clearance of pills can lead to acute inflammation. Oesophageal damage occurs when the caustic contents of a drug remain in the oesophagus long enough to produce mucosal lesions. Taking medications at bedtime or without fluids is a common cause of oesophagitis.

The possibility of drug-related damage should be suspected in all cases of oesophagitis, chest pain and dysphagia. History and gastrointestinal endoscopy will confirm the diagnosis. Treatment is supportive, although acid reduction is used frequently as an adjunct. This review reflects the current state of knowledge in this field.

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References

  1. Boyce HW. Drug-induced esophageal damage: diseases ofmedical progress. Gastrointest Endosc 1998; 47: 547–50

    PubMed  Google Scholar 

  2. Boyce HW. Drug-induced esophageal and gastric damage. In: Tytgat GNJ, van Blankenstein M, editors. Current topics in gastroenterology and hepatology. New York: Georg Thieme Verlag, 1996: 170–95

    Google Scholar 

  3. Kikendall JW. Pill-induced esophageal injury. Gastroenterol Clin North Am 1991; 20: 835–46

    CAS  PubMed  Google Scholar 

  4. Kikendall JW, Friedman AC, Oyewole MA. Pill-induced esophageal injury: case reports and review of the medical literature. Dig Dis Sci 1983; 28: 174–82

    CAS  PubMed  Google Scholar 

  5. Jaspersen D. Extragastric side effects of NSAIDs. Dtsch Med Wschr 1998; 132: 669–73

    Google Scholar 

  6. Bott S, Prakash C,McCallumRW.Medication-induced esophageal injury: survey of the literature. AmJ Gastroenterol 1987; 758–63

  7. Goldberg NE, Ott MJ, Parker-Hartigan L. Medication-induced oesophagitis. J Pediatr Health Care 1996; 10: 35–6

    CAS  PubMed  Google Scholar 

  8. Collins FJ,Matthews HR, Baker SE. Drug induced oesophagealinjury. BMJ 1979; 1: 1673–6

    Google Scholar 

  9. Perry PA, Dean BS, Krenelok EP. Drug induced esophageal injury. Clin Toxicol 1989; 27: 281–6

    CAS  Google Scholar 

  10. Kalar JG, Redwine JN, Persaud MV. Iatrogenic oesophagitis. Iowa Med 1988; 78: 323–6

    CAS  PubMed  Google Scholar 

  11. Puhakha HJ. Drug-induced corrosive injury of the oesophagus. J Laryngol Otol 1978; 92: 927–31

    Google Scholar 

  12. Hunert H, Ottenjann R. Drug-induced oesophageal ulcers [letter]. Gastrointest Endosc 1979; 25: 41

    Google Scholar 

  13. Teplick JG, Teplick SK, Ominsky SH, Haskin ME. Oesophagitis caused by oral medication. Radiology 1980; 134: 23–5

    CAS  PubMed  Google Scholar 

  14. Agha FP, Wilson JAP, Nostrand TT. Medication-induced oesophagitis. Gastrointest Radiol 1986; 11: 7–11

    CAS  PubMed  Google Scholar 

  15. Levine MS. Drug-induced, caustic and radiation oesophagitis. In: Levine MA, editor. Radiology of the oesophagus. Philadelphia: WB Saunders, 1989: 73–89

    Google Scholar 

  16. Levine MS. Other oesophagitides. In: Fore RM, Levine MS, Laufer I, editors. Textbook of gastrointestinal radiology. Philadelphia: WB Saunders, 1994: 403–30

    Google Scholar 

  17. Pemberton J. Oesophageal obstruction and ulceration caused by oral potassium therapy. Br Heart J 1970; 32: 267–8

    CAS  PubMed Central  PubMed  Google Scholar 

  18. Goyal RK. Diseases of oesophagus. In: Isselbacher KL, Braunwald E, editors. Harrison’s principles of internal medicine. New York: McGraw-Hill, 1994: 1355

    Google Scholar 

  19. Richter JE.Motility disorders of the oesophagus. In: Yamada T. Textbook of gastroenterology. Philadelphia: Lippincott, 1991: 1083

    Google Scholar 

  20. Lobis IF, Fisher R. Anticholinergics therapy for achalasia: a controlled trial [abstract]. Gastroenterology 1976; 70: 976

    Google Scholar 

  21. Gelfand M, Rozen P, Keren S, et al. Effect of nitrates on LOS pressure in achalasia: a potential therapeutic aid. Gut 1981; 22 (4): 312–8

    Google Scholar 

  22. Gelfand M, Rozen P, Gilat T. Isosorbide dinitrate and nifedipine treatment of achalasia: a clinical, manometric and radionuclide evaluation. Gastroenterology 1982; 83: 963–8

    Google Scholar 

  23. Carlborg B, Densert O. Medikamentella esofagusstrikturer. Lakartidningen 1978; 75: 4609–11

    CAS  PubMed  Google Scholar 

  24. Wright V. The oesophagus. In: Walker P, Durie JR, Hamilton JA, et al, editors. Pediatric gastrointestinal disease: pathophysiology, diagnosis and management, vol. I. Philadelphia: BC Decker Inc., 1991: 375–6

    Google Scholar 

  25. Ecker GA, Karsch J. Naproxen induced ulcerative esophagitis. J Rheumatol 1992; 19: 646–7

    CAS  PubMed  Google Scholar 

  26. Marvola M, Rajaniemi M, Marttila E. Effect of dosage form and formulation factors on the adherence of drugs to the oesophagus. J Pharm Sci 1983; 72: 1034–6

    CAS  PubMed  Google Scholar 

  27. Channer KS, Virjee JP. The effect of size and shape of tablets on their oesophageal transit. J Clin Pharmacol 1986; 26: 141–6

    CAS  PubMed  Google Scholar 

  28. Hey H, Jorgensen F, Sorensen K, et al. Oesophageal transit of six commonly used tablets and capsules. BMJ 1982; 285: 1717–9

    CAS  PubMed  Google Scholar 

  29. Carlborg B, Densert O. Esophageal lesions caused by orally administered drugs. Eur Surg Res 1980; 12: 270–82

    CAS  PubMed  Google Scholar 

  30. Cohen S, Fisher R, Lipshutz W, et al. The pathogenesis of oesophageal dysfunction in scleroderma andRaynaud’s disease. J Clin Invest 1972; 51 (10): 2663–8

    CAS  PubMed Central  PubMed  Google Scholar 

  31. Zamost BJ, Hirschberg J, Ippoliti AF. Oesophagitis in scleroderma: prevalence and risk factors. Gastroenterology 1987; 92 (2): 421–8

    CAS  PubMed  Google Scholar 

  32. Katzka DA, Reynolds JC, Saul SH. Barrett’s metaplasia and adenocarcinoma of the oesophagus in scleroderma.AmJMed 1987; 82 (1): 46–52

    CAS  Google Scholar 

  33. Mason SJ, O’Meara TF. Drug-induced esophagitis. J Clin Gastroenterol 1981; 3: 115–20

    CAS  PubMed  Google Scholar 

  34. Carlborg B, Densert O, Lindqvist C. Tetracycline induced esophageal ulcers: a clinical and experimental study. Laryngoscope 1983; 93: 184–7

    CAS  PubMed  Google Scholar 

  35. O’Meara TF. Anew endoscopic finding of tetracycline-induced oesophageal ulcers. Gastrointest Endosc 1980; 26: 106–7

    PubMed  Google Scholar 

  36. Burke EL. Acute oesophageal damage from one brand of tetracycline tablets [letter]. Gastroenterology 1975; 68: 1022

    Google Scholar 

  37. Stillman AE, Martin RJ. Tetracycline-induced oesophageal ulcerations [letter]. Arch Dermatol 1979; 115 (8): 1005

    CAS  PubMed  Google Scholar 

  38. Aarons B, Bruns BJ. Oesophageal ulceration associated with ingestion of doxycycline [letter]. N Z Med J 1980; 91 (651): 27

    CAS  PubMed  Google Scholar 

  39. Beel RJ. Tetracycline induced esophagitis. Al Med 1986; 50: 47–50

    Google Scholar 

  40. Crowson TD, Head LD, Ferrante WA. Oesophageal ulcers associated with tetracycline therapy. JAMA 1976; 235: 2747–8

    CAS  PubMed  Google Scholar 

  41. Schneider R. Doxycycline oesophageal ulcers. Dig Dis 1977; 22: 805 - 7

    CAS  Google Scholar 

  42. Channer KS, Hollanders D. Tetracycline induced oesophageal ulceration. BMJ 1981; 282: 1359–60

    CAS  PubMed  Google Scholar 

  43. Delpre GK. Oesophageal ulceration due to enterocoated doxycycline therapy [letter]. Gastrointest Endosc 1981; 27: 109

    Google Scholar 

  44. Fraser GM, Odes HS, Krugliak P. Severe localised oesophagitis due to doxycycline. Endoscopy 1987; 19: 86

    CAS  PubMed  Google Scholar 

  45. Evans KT, Toberts GM. Where do all the tablets go? Lancet 1976; II: 1237–9

    Google Scholar 

  46. Applegate GR,Malmud LS, Rock E. It’s a hard pill to swallow: or don’t take it lying down [letter]. Gastroenterology 1980; 78: 1132

    Google Scholar 

  47. Sutton DR, Gosnold JK. Oesophageal ulceration due to clindamycin [letter]. BMJ 1977; 1: 1598

    CAS  PubMed  Google Scholar 

  48. Gould PC, Bartolomeo RS, Sklarek HM. Oesophageal ulceration associated with oral penicillin in Marfan’s syndrome. NY State J Med 1985; 85: 199–200

    CAS  Google Scholar 

  49. Mortimer O, Wiholm BE. Oesophageal injury associated with pivmecillinam tablets. Eur J Clin Pharmacol 1989; 37: 605–7

    CAS  PubMed  Google Scholar 

  50. Taha A, Nakshabendi L, Sturrock RD. Nonsteroidal anti-inflammatory drugs (NSAIDs) and the oesophagus–endoscopic and histologic studies. J Clin Pathol 1994; 47: 705–8

    CAS  PubMed  Google Scholar 

  51. Talley NJ, Evans JM, Fleming KC, et al. Nonsteroidal anti-inflammatory drugs and dyspepsia in the elderly. Dig Dis Sci 1995; 40: 1345–50

    CAS  PubMed  Google Scholar 

  52. El-Serag HB, Sonnenberg A. Association of esophagitis and esophageal strictures with disease treated with non-steroidal anti-inflammatory drugs. Am J Gastroenterol 1997; 92: 52–6

    CAS  PubMed  Google Scholar 

  53. Levine MS, Borislow SM, Rubesin SE, et al. Esophageal stricture caused by a motrin tablet (ibuprofen). Abdom Imaging 1994; 19: 6–7

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  55. Schreiber JB, Covington JA. Aspirin-induced oesophageal hemorrhage. JAMA 1988; 259: 1647–8

    CAS  PubMed  Google Scholar 

  56. Bonavina L, DeMeester TR,McChesney L. Drug-induced esophageal strictures. Ann Surg 1987; 206: 173–83

    CAS  PubMed  Google Scholar 

  57. Kikendall JW, Schmidt M, Graeber GM. Pill-induced esophageal ulceration and stricture following cardiac surgery. Milit Med 1986; 151: 539–42

    CAS  Google Scholar 

  58. Heller SR, Fellows IW, Ogilvie AL, et al. Non-steroidal anti-inflammatory drugs and benign oesophageal stricture. BMJ (Clin Res Ed) 1982; 285: 167–8

    CAS  Google Scholar 

  59. Wilkins WE, Ridley MG, Pozniak AL. Benign strictures of the oesophagus: role of non-steroidal anti-inflammatory drugs. Gut 1984; 25: 478–80

    CAS  PubMed  Google Scholar 

  60. Lanas A, Hirschowitz BI. Significance of aspirin use in patients with esophagitis. J Clin Gastroenterol 1991; 13: 622–7

    CAS  PubMed  Google Scholar 

  61. Lédinghen V, Mannant PR, Foucher J. Non-steroidal anti-inflammatory drugs and variceal bleeding: a case-control study. J Hepatol 1996; 24: 570–3

    PubMed  Google Scholar 

  62. Wilcox CM, Shalek KA, Cotsonis G. Striking prevalence of over-the-counter-nonsteroidal anti-inflammatory drug use in patients with upper gastrointestinal hemorrhage. Arch Intern Med 1994; 154: 42–6

    CAS  PubMed  Google Scholar 

  63. Semble EL, Wu WC, Castell DO. Nonsteroidal anti-inflammatory drugs and esophageal injury. Semin Arthritis Rheum 1989; 19: 99–109

    CAS  PubMed  Google Scholar 

  64. Sun DCH, Roth SH, Mitchell CS, et al. Upper gastrointestinal disease in rheumatoid arthritis. AmJ Dig Dis 1974; 19 405–10

    CAS  Google Scholar 

  65. Shallcross TM,Wyatt JI, Rathhone BJ, et al. Non-steroidal anti-inflammatory drugs, hiatus hernia, and Helicobacter pylori, in patients with oesphageal ulceration. Br J Rheumatol 1990; 29: 288–90

    CAS  PubMed  Google Scholar 

  66. De Groen PC, Lubbe DF, Laurence CB. Esophagitis associated with the use of alendronate. N Engl J Med 1996; 335: 1016–21

    CAS  PubMed  Google Scholar 

  67. Graham DY, Malaty HM, Goodgame R. Primary aminobiphosphonates: a new class of gastrotoxic drugs–comparison of alendronate and aspirin. Am J Gastroenterol 1997; 92: 1322–5

    CAS  PubMed  Google Scholar 

  68. Colina RE, Smith M, Kikendall JW, et al. A new probable increasing cause of esophageal uleration: alendronate. Am J Gastroenterol 1997; 92: 704–6

    CAS  PubMed  Google Scholar 

  69. Lanza Fl, Carlson MR. The effects of amino versus alkylbiphosphonates on the healing of aspirin-induced stomach erosions in healthy subjects [abstract]. Am J Gastroenterol 1996; 91: 1916

    Google Scholar 

  70. Francis RM. Oral bisphosphonates in the treatment of osteoporosis: a review. Curr Ther Res 1995; 56: 831–51

    CAS  Google Scholar 

  71. BlankMA, Ems BL, Gibson GW. Nonclinicalmodel for assessing gastric effects of bisphosphonates. Dig Dis Sci 1997; 42: 281–8

    Google Scholar 

  72. Adami S,MianM, Gatti P. Effects of two oral doses of alendronate in the treatment of Paget’s disease of bone. Bone 1994: 15: 415–7

    Google Scholar 

  73. Liberman, UA, Hirsch LJ. Esophagitis and alendronate. N Engl J Med 1996; 335: 1069–70

    CAS  PubMed  Google Scholar 

  74. Maconi G, Porro GB. Multiple ulcerative oesophagitis caused by alendronate. Am J Gastroenterol 1995; 90: 1889–90

    CAS  PubMed  Google Scholar 

  75. Abdelmalek MF, Douglas DD. Alendronate-induced ulcerative oesophagitis [letter]. Am J Gastroenterol 1996; 91: 1282–3

    CAS  PubMed  Google Scholar 

  76. Rosenthal T, Adar R,Mililthianu J. Oesophageal ulceration and oral potassium chloride ingestion. Chest 1974; 65: 463–5

    CAS  Google Scholar 

  77. Henry JG, Shinner JJ, Martino JH. Fatal oesophageal and bronchial artery ulceration caused by solid potassium chloride. Pediatr Cardiol 1983; 4: 251–2

    CAS  PubMed  Google Scholar 

  78. Lowry N, Delaney P, O’Malley E. Oesophageal ulceration due to slow-release potassiumin the presence of left atrial enlargement. Ir J Med Sci 1975; 144: 366

    Google Scholar 

  79. Lubbe WF, Cadogan ES, Kannemeyer AHR. Oesophageal ulceration due to slow-release potassium in the presence of left atrial enlargement. N Z Med J 1979: 90: 377–9

    CAS  PubMed  Google Scholar 

  80. Bohane TD, Perrault J, Fowler RS. Oesophagitis and oesophageal obstruction from quinidine tablets in association with left atrial enlargement. Aust Paediatr J 1978; 14: 191–2

    CAS  PubMed  Google Scholar 

  81. Creteur V, Laufer I, Kressel HY, et al. Drug-induced oesophagitis detected by double-contrast radiography. Radiology 1983; 147: 365–8

    CAS  PubMed  Google Scholar 

  82. Tobias R, Cullis S, Kottler RE. Emepronium bromide-induced oesophagitis. S Afr Med J 1982; 61: 368–70

    CAS  PubMed  Google Scholar 

  83. Hillman LC, Scobie BA, Pomare EW. Acute oesophagitis due to emepronium bromide. N Z Med J 1981; 94: 4–6

    Google Scholar 

  84. Kavin H. Oesophageal ulceration due to emepronium bromide. Lancet 1977; I: 424–5

    Google Scholar 

  85. Stoller JL. Oesophageal ulceration and theophylline [letter]. Lancet 1985: II: 328–9

    Google Scholar 

  86. Enzenauer RW, Bass JW,McDonnell JT. Esophageal ulceration associated with oral theophylline [letter]. N Engl JMed 1984; 310: 261

    CAS  Google Scholar 

  87. Stiris MG, Oyen D. Oesophagitis caused by oral ingestion of Aptin (alprenolol chloride) Durettes. Eur J Radiol 1982; 2: 28–40

    Google Scholar 

  88. Olovson SG, Havo N, Regardh CG. Oesophageal ulcerations and plasma levels of different alprenolol salts: potential implications for the clinic. Acta Pharmacol Toxicol 1986; 58: 55–60

    CAS  Google Scholar 

  89. AlMahdy H, Boswell GV. Captopril-induced oesophagitis. Eur J Clin Pharmacol. 1988; 3 (1) 4: 95.

    Google Scholar 

  90. Walsh J, Kneafsey DV. Phenobarbitone induced oesophagitis. Ir Med J 1980; 73 (10): 399

    CAS  PubMed  Google Scholar 

  91. Pen J, Van Meerbeeck J, Pelekmans P. Thiazinium-induced oesophageal ulcerations. Acta Clin Belg 1986; 41: 278–83

    CAS  PubMed  Google Scholar 

  92. Walta DC, Giddens JD, Johnson LF. Localized proximal oesophagitis secondary to ascorbic acid ingestion and oesophageal motor disorder. Gastroenterology 1976; 70: 766–9

    CAS  PubMed  Google Scholar 

  93. Abbarah TR, Fredell JE, Ellenz GB. Ulceration by oral ferrous sulfate. JAMA 1976; 236: 2320

    Google Scholar 

  94. Copenhagen Oesophageal Varices Sclerotherapy Project: a randomized multicenter trial. N Engl J Med 1984; 311: 1594–1600

    Google Scholar 

  95. Korula J, Balert LA, Radvan G, et al. Aprospective randomized controlled trial of chronic oesophageal sclerotherapy. Hepatology 1985; 5: 584–9

    CAS  PubMed  Google Scholar 

  96. Sarin SK, Sachdev G, Nanda R, et al. Comparison of the two time schedules for endoscopic sclerotherapy: a prospective randomized controlled study. Gut 1986; 27: 710–3

    CAS  PubMed  Google Scholar 

  97. Levine MS. Drug-induced disorders of the esophagus. Abdom Imaging 1999; 24: 3 –8

    CAS  PubMed  Google Scholar 

  98. Levine MS, Laufer I, Kressel HY, et al. Herpes oesophagitis. AJR 1981; 136: 863–6

    CAS  PubMed  Google Scholar 

  99. Shortsleeve MJ, Levine MS. Herpes oesophagitis in otherwise healthy patients: clinical and radiographic findings. Radiology 1992; 182: 859–61

    CAS  PubMed  Google Scholar 

  100. LevineMS,Macones AJ, Laufer I. Candida oesophagitis–accuracy of radiographic diagnosis. Radiology 1985; 154: 581–7

    Google Scholar 

  101. Gobel V, Long BW, Richter G. Aphthous ulcers in the oesophagus with Crohn colitis. AJR 1981; 137: 872–3

    Google Scholar 

  102. Levine MS, Loercher G, Katzka DA, et al. Giant human immunodeficiency virus-related ulcers in the oesophagus. Radioloy 1991; 180: 323–6

    CAS  Google Scholar 

  103. Sur S, Levine MS, Kowalski TE, et al. Giant ulcers of the oesophagus in patients with human immunodeficiency virus: clinical, radiographic, and pathologic findings. Radiology 1995; 194: 447–51

    Google Scholar 

  104. Weerda H, Brand ET. Stevens-Johnson syndrome with oesophagitis. HNO 1974; 22: 246–8

    CAS  PubMed  Google Scholar 

  105. Pinos T, Figueras C,Mar R. Doxicycline-induced oesophagitis: treatment with liquid sucralphate. Am J Gastroenterol 1990; 85: 902–3

    CAS  PubMed  Google Scholar 

  106. Pleet D, Malmud LS, Maurer A. Sucralphate binding to inflamed oesophageal mucosa. Gastroenterology 1985; 88: 1540–1

    Google Scholar 

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Acknowledgements

This paper is dedicated to Professor Dr Rudolf Arnold, Department of Gastroenterology, University Hospital Marburg, Germany.

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  1. Department of Gastroenterology, Academic Medical Hospital, Pacelliallee 4-6, D-36043, Fulda, Germany

    Daniel Jaspersen

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Jaspersen, D. Drug-Induced Oesophageal Disorders. Drug-Safety 22, 237–249 (2000). https://doi.org/10.2165/00002018-200022030-00007

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