Skip to main content

Drug Interactions with Antacids

Mechanisms and Clinical Significance

Drug Safety volume 11, pages 395–407 (1994)Cite this article

Summary

Concomitant use of antacid preparations with other medications is common. The potential for antacid-drug interactions is dependent upon the chemistry and physical properties of the antacid preparation. The intragastric release of free aluminum and magnesium ions has potent effects on gastrointestinal function and on drug pharmacokinetics. Antacid-drug interactions may occur secondary to changes in gastrointestinal motility or alterations in gastric and urinary pH. Direct adsorption also results in decreased drug bioavailability. Human drug interaction studies are usually performed with healthy volunteers; extrapolation of these results to clinical situations may not always be valid. However, the current literature would suggest that significant interactions with antacids do occur with certain members of the quinolone, nonsteroidal anti-inflammatory drug (NSAID) and cephalosporin classes of drugs. Notable interactions also occur with tetracycline, quinidine, ketoconazole and oral glucocorticoids. These interactions are particularly relevant in the patient with sepsis, cardiac disease or inflammatory syndromes.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

USD 49.95

Price includes VAT (USA)
Tax calculation will be finalised during checkout.

References

  1. Statistics Canada. The Health of Canadians. Report of the Canada Health Survey. Ottawa, Ontario: Health and Welfare Canada, 1982: CN 82-538E

  2. Compendium of pharmaceuticals and specialties. Ottawa: Canadian Pharmaceutical Association, 1994

  3. Brunton LL. Agents for control of gastric acidity and control of peptic ulcers. In: Gilman AG, Rall TW, Nies AS, et al., editors. The pharmacologic basis of therapeutics. 8th edition. New York: Pergamon Press, 1990: 897–913

    Google Scholar 

  4. Nail SL, White JL, Hem SL. Structure of aluminum hydroxide gel I: initial precipitate. J Pharm Sci 1976; 65: 1188–91

    PubMed  CAS  Google Scholar 

  5. Hava M, Hurwitz A. The relaxing effect of aluminum and lanthanum on rat and human gastric smooth muscle in vitro. Eur J Pharmacol 1973; 22: 156–61

    PubMed  CAS  Google Scholar 

  6. Crohn BB, Rosenek BD. An exhibition of books shown at the graduate fortnight illustrating the progress of gastroenterology. Bull NY Acad Med 1935; 11: 74

    Google Scholar 

  7. Van Goidsenhoven GMT, Gray OV, Price AV, et al. The effect of prolonged administration of large doses of sodium bicarbonate in man. Clin Sci 1954; 13: 383

    Google Scholar 

  8. Narins RG, Jones ER, Townsend R, et al. Metabolic acid-base disorders: pathophysiology, classification and treatment. In: Arieff AI, Defronzo RA, editors. Fluid electrolyte and acid-base disorders. New York: Churchill Livingstone, 1985: 269–384

    Google Scholar 

  9. Walan A. Metabolic side-effects and interactions. Scand J Gastroenterol Suppl 1982; 75: 63–8

    PubMed  CAS  Google Scholar 

  10. Fine DF, Santa Ana CA, Fordtran JS. Diagnosis of magnesium-induced diarrhea. N Engl J Med 1991; 324: 1012–7

    PubMed  CAS  Google Scholar 

  11. Rohner HG, Wienbeck M. Effect of antacid treatment on bowel habits. In: Halter F, editor. Antacids in the eighties. Munich: Urban and Schwarzenberg, 1982: 107–11

    Google Scholar 

  12. Ritschell WA. Antacids and other drugs in GI diseases. Hamilton: Drug Intelligence Publications, 1984: 60

    Google Scholar 

  13. Hurwitz A, Robinson RG, Tribhawan VS. Effects of antacids on gastric emptying. Gastroenterology 1976; 71: 268–73

    PubMed  CAS  Google Scholar 

  14. Marano AR, Caride VJ, Prokop EK. Effect of sucralfate and an aluminum hydroxide gel on gastric emptying of solids and liquids. Clin Pharmacol Ther 1985; 37: 629–32

    PubMed  CAS  Google Scholar 

  15. Lux G, Hartog C, Ruppin H. Combined acid secretion and gastric emptying under antacid and pirenzepine. In: Halter F, editor. Antacids in the eighties. Munich: Urban and Schwarzenberg, 1982: 57–63

    Google Scholar 

  16. Riley SA, Sutcliffe F, Kim M, et al. The influence of gastrointestinal transit on drug absorption in healthy volunteers. Br J Clin Pharmacol 1992; 34: 32–9

    PubMed  CAS  Google Scholar 

  17. Nimmo W. Gastric emptying and drug absorption. In: Prescott LF, Nimmo WS, editors. Drug absorption. New York: ADIS Press, 1979: 11–20

    Google Scholar 

  18. Nimmo WS. Drugs, diseases and altered gastric emptying. Clin Pharmacokinet 1976; 1: 189–203

    PubMed  CAS  Google Scholar 

  19. Hurwitz A. Gastrointestinal drug absorption: effects of antacids. In: Morselli PL, Garattini S, Cohen SN, editors. Drug interactions. New York: Raven Press, 1974: 21–32

    Google Scholar 

  20. Strom M. Antacid side-effects on bowel habits. Scand J Gastroenterol Suppl 1982; 75: 54–62

    PubMed  CAS  Google Scholar 

  21. Erckenbrecht J, Kienle U, Zollner L, et al. Effects of high dose antacids on bowel motility. Digestion 1982; 25: 244–7

    PubMed  CAS  Google Scholar 

  22. Binder AJ, Donowitz M. Clinical trends and topics. A new look at laxative action. Gastroenterology 1975; 69: 1001–5

    PubMed  CAS  Google Scholar 

  23. Wanitschke R, Ammon HV. Effects of magnesium sulfate on transit time and water transport in the human jejunum. Gastroenterology 1976; 70: 949–50

    Google Scholar 

  24. Sezaki H, Muranishi S, Nakamura J. Absorption of polar acids and bases. In: Prescot LF, Nimmo WS, editors. Drug absorption. New York: ADIS Press, 1981: 35–60

    Google Scholar 

  25. Gibaldi M, Grundhofer B, Levy G. Effect of antacids on pH of urine. Clin Pharmacol Ther 1974; 16: 520–5

    PubMed  CAS  Google Scholar 

  26. Gibaldi M, Grundhofer B, Levy G. Time course and dose dependence of antacid effect on urine pH. J Pharm Sci 1975; 64: 2000–4

    Google Scholar 

  27. Gerhardt RE, Knouss RF, Thyrum PT. Quinidine excretion in aciduria and alkaluria. Ann Intern Med 1969; 71: 927–33

    PubMed  CAS  Google Scholar 

  28. Levy G, Lampman T, Kamath BL. Decreased serum salicylate concentrations in children with rheumatic fever treated with antacid. N Engl J Med 1975; 293: 323–5

    PubMed  CAS  Google Scholar 

  29. Hansten PD, Hayton WL. Effect of antacid and ascorbic acid on serum salicylate concentration. J Clin Pharm 1980; 20: 326–31

    CAS  Google Scholar 

  30. D’Arcy PF, McElnay JC. Drug-metal ion interaction in the gut. In: Sigel H, editor. Metal ions in biological systems. New York: Marcel Dekker Inc., 1973: 1–36

    Google Scholar 

  31. Garty M, Hurwitz A. Effect of Cimetidine on absorption of oral tetracycline in mice. Pharmacology 1980; 20: 155–9

    PubMed  CAS  Google Scholar 

  32. Garty M, Hurwitz A. Effect of Cimetidine and antacids on gastrointestinal absorption of tetracycline. Clin Pharmacol Ther 1980; 28: 203–7

    PubMed  CAS  Google Scholar 

  33. Khalil SA. The uptake of digoxin and digitoxin by some antacids. J Pharm Pharmacol 1974; 26: 961–7

    PubMed  CAS  Google Scholar 

  34. Kulshrestha VK, Thomas M, Wadsworth J, et al. Interaction between phenytoin and antacids. Br J Clin Pharmacol 1978; 6: 177–9

    PubMed  CAS  Google Scholar 

  35. Brown DD, Juhl RP. Decreased bioavailability of digoxin due to antacids and kaolin-pectin. N Engl J Med 1976; 295: 1034–7

    PubMed  CAS  Google Scholar 

  36. McElnay JC, D’Arcy PR Sites and mechanisms of drug interactions 1. In vivo, intestinal and metabolic interactions. Int J Pharm 1980; 5: 167–85

    CAS  Google Scholar 

  37. Neuvonen PJ. Drug absorption interactions. In: Prescott LF, Nimmo WS, editors. Drug absorption. New York: ADIS Press, 1981: 228–37

    Google Scholar 

  38. Barr WH, Adir J, Garretson L. Decrease of tetracycline absorption in man by sodium bicarbonate. Clin Pharmacol Ther 1971; 12: 779–84

    PubMed  CAS  Google Scholar 

  39. Gugler R, Allgayer H. Effects of antacids on the clinical pharmacokinetics of drugs: an update. Clin Pharmacokinet 1990; 18: 210–9

    PubMed  CAS  Google Scholar 

  40. Reynolds JC. The clinical importance of drug interactions with antiulcer therapy. J Clin Gastroenterol 1990; 12 Suppl. 2: S54–63

    PubMed  Google Scholar 

  41. D’Arcy PF, McElnay JC. Drug-antacid interactions assessment of clinical importance. Drug Intell Clin Pharm 1987; 21: 607–17

    PubMed  Google Scholar 

  42. Moustafa MA, AL-Shora H, Gaber M. Decreased bioavailability of quinidine sulphate due to interactions with adsorbant antacids and antidiarrheal mixture. Int J Pharm 1987; 34: 207–11

    CAS  Google Scholar 

  43. Remon JP, Belpaire F, Van Severen R, et al. Interaction of antacids with antiarrhythmics. V. Effect of aluminium hydroxide and magnesium oxide on the bioavailability of quinidine, procainamide and propranolol in dogs. Arzneimittelforschung 1983; 33: 117–20

    PubMed  CAS  Google Scholar 

  44. Ace LN, Jaffe JM, Kunka RL. Effect of food and antacid on quinidine boavailability. Biopharm Drug Dispos 1983; 4: 183–90

    PubMed  CAS  Google Scholar 

  45. Romankiewicz JA, Reidenberg M, Drayer D, et al. The noninterference of aluminum hydroxide gel with quinidine sulfate absorption: an approach to control quinidine-induced diarrhea. Am Heart J 1978; 96: 518–20

    PubMed  CAS  Google Scholar 

  46. Zin MB. Quinidine intoxication from alkali ingestion. Tex Med 1970; 66 (12): 64–6

    Google Scholar 

  47. McElnay JC, D’Arcy PF, Leonard JK. The effect of activated dimethicone, other antacid constituents and kaolin on the absorption of propranolol. Experientia 1982; 38: 605–6

    PubMed  CAS  Google Scholar 

  48. Dobbs JH, Skoutakis VA, Acchardo SR. Effects of aluminum hydroxide on the absorption of propranolol. Curr Ther Res 1976; 21: 887–92

    Google Scholar 

  49. Hong CY, Hu SC, Lin SJ, et al. Lack of influence of aluminum hydroxide on the bioavailability and beta-adrenoceptor blocking activity of propranolol. Int J Clin Pharmacol Ther Toxicol 1985; 23: 244–6

    PubMed  CAS  Google Scholar 

  50. McElnay JC, Temple DJ. The use of buccal partitioning as a model to examine the effects of aluminium hydroxide gel on the absorption of propranolol. Br J Clin Pharmacol 1982; 13: 399–403

    PubMed  CAS  Google Scholar 

  51. Regardh CG, Lundborg P, Persson BA. The effect of antacid, metoclopramide, and propantheline on the bioavailability of metoprolol and atenolol. Biopharm Drug Dispos 1981; 2: 79–87

    PubMed  CAS  Google Scholar 

  52. Mantyla R, Mannisto PT, Vuorela A, et al. Impairment of Captopril bioavailability by concomitant food and antacid intake. Int J Clin Pharmacol Ther Toxicol 1984; 22: 626–9

    PubMed  CAS  Google Scholar 

  53. Shionoiri H. Pharmacokinetic drug interactions with ACE inhibitors. Clin Pharmacokinet 1993; 25: 20–58

    PubMed  CAS  Google Scholar 

  54. Rahm V, Schacht P. Safety of ciprofloxacin. A review. Scand J Infect Dis Suppl 1989; 60: 120–8

    PubMed  CAS  Google Scholar 

  55. Bergeron MG. The pharmacokinetics and tissue penetration of the fluoroquinolones. Clin Invest Med 1989; 12: 20–7

    PubMed  CAS  Google Scholar 

  56. Hoffken G, Borner K, Glatzel PD. Reduced enteral absorption of ciprofloxacin in the presence of antacids. Eur J Clin Microbiol Infect Dis 1985; 4: 345–8

    CAS  Google Scholar 

  57. Noyes M, Polk RE. Norfloxacin and absorption of magnesium-aluminum. Ann Intern Med 1988; 109: 168–9

    PubMed  CAS  Google Scholar 

  58. Fleming LW, Moreland TA, Stewart WK, et al. Ciprofloxacin and antacids. Lancet 1986; 2: 294

    PubMed  CAS  Google Scholar 

  59. Golper TA, Hartstein AI, Morthland VH, et al. Effects of antacids and dialysate dwell times on multiple-dose pharmacokinetics of oral ciprofloxacin in patients on continuous ambulatory peritoneal dialysis. Antimicrob Agents Chemother 1987; 31: 1787–90

    PubMed  CAS  Google Scholar 

  60. Preheim LC, Cuevas TA, Roccaforte JS, et al. Ciprofloxacin and antacids. Lancet 1986; 2: 48

    PubMed  CAS  Google Scholar 

  61. Nix DE, Wilton JH, Schentag JJ, et al. Inhibition of norfloxacin absorption by antacids and sucralfate. Rev Infect Dis 1989; 11 Suppl. 5: S1096

    Google Scholar 

  62. Frost RW, Lasseter KC, Noe AJ, et al. Effects of aluminum hydroxide and calcium carbonate antacids on the bioavailability of ciprofloxacin. Antimicrob Agents Chemother 1992; 36: 830–2

    PubMed  CAS  Google Scholar 

  63. Nix DE, Watson WA, Lerner ME, et al. Effects of aluminum and magnesium antacids and ranitidine on the absorption of ciprofloxacin. Clin Pharmacol Ther 1989; 46: 700–5

    PubMed  CAS  Google Scholar 

  64. Flor S, Guay DR, Opsahl JA, et al. Effects of magnesium-aluminum hydroxide and calcium carbonate antacids on bioavailability of ofloxacin. Antimicrob Agents Chemother 1990; 34: 2436–8

    PubMed  CAS  Google Scholar 

  65. Tanaka M, Kurata T, Fujisawa C, et al. Mechanistic study of inhibition of levofloxacin absorption by aluminum hydroxide. Antimicrob Agents Chemother 1993; 37: 2173–8

    PubMed  CAS  Google Scholar 

  66. Deppermann KM, Lode H. Fluoroquinolones interaction profile during enteral absorption. Drugs 1993; 45 Suppl. 3: 65–72

    PubMed  Google Scholar 

  67. Shimada J, Shiba K, Oguma T, et al. Effect of antacid on absorption of the quinolone lomefloxacin. Antimicrob Agents Chemother 1992; 36: 1219–24

    PubMed  CAS  Google Scholar 

  68. Shiba K, Saito A, Shimada J, et al. Interactions of fleroxacin with dried aluminum hydroxide gel and probenecid. Rev Infect Dis 1989; 11 Suppl. 5: 18–9

    Google Scholar 

  69. Grasela TH, Schentag JJ, Sedman AJ, et al. Inhibition of en-oxacin absorption by antacids or ranitidine. Antimicrob Agents Chemother 1989; 33: 615–7

    PubMed  CAS  Google Scholar 

  70. Foster T, Blouin R. The effect of an antacid timing on lomefloxacin bioavailability. Pharmacotherapy 1991; 11: 101

    Google Scholar 

  71. Sorgel F, Naber KG, Jauhde U, et al. Brief report: gastrointestinal secretion of ciprofloxacin. Evaluation of the charcoal model for investigations in healthy volunteers. Am J Med 1989; 87 Suppl. 5A: 62s–65s

    PubMed  CAS  Google Scholar 

  72. Van der Meer JWM, Keuning JJ, Scheijgrond HW, et al. The influence of gastric acidity on the bio-availability of ketoconazole. J Antimicrob Chemother 1980; 6: 552–4

    Google Scholar 

  73. Daneshmend TK, Warnock DW. Clinical pharmacokinetics of ketoconazole. Clin Pharmacokinet 1988; 14: 13–34

    PubMed  CAS  Google Scholar 

  74. Daneshmend TK, Warnock DW, Ene MD, et al. Influence of food on the pharmacokinetics of ketoconazole. Antimicrob Agents Chemother 1984; 25: 1–3

    PubMed  CAS  Google Scholar 

  75. Schafer Korting M. Pharmacokinetic optimisation of oral antifungal therapy. Clin Pharmacokinet 1993; 25: 329–41

    PubMed  CAS  Google Scholar 

  76. Thorpe JE, Baker N, Bromet Petit M. Effect of oral antacid administration on the pharmacokinetics of oral fluconazole. Antimicrob Agents Chemother 1990; 34: 2032–3

    PubMed  CAS  Google Scholar 

  77. Lazar JD, Wilner KD. Drug interactions with fluconazole. Rev Infect Dis 1990; 12 Suppl. 3: S327–33

    PubMed  CAS  Google Scholar 

  78. Hughes GS, Heald DL, Barker KB, et al. The effects of gastric pH and food on the pharmacokinetics of a new oral cephalosporin, Cefpodoxime proxetil. Clin Pharmacol Ther 1989; 46: 674–85

    PubMed  CAS  Google Scholar 

  79. Sommers DK, Van Wyk M, Moncrieff J, et al. Influence of food and reduced gastric acidity on the bioavailability of cefuroxime axetil. Br J Clin Pharmacol 1984; 18: 535–9

    PubMed  CAS  Google Scholar 

  80. Deppermann KM, Lode H, Hoffken G, et al. Influence of ranitidine, pirenzepine, and aluminum magnesium hydroxide on the bioavailability of various antibiotics, including amoxicillin, cephalexin, doxycycline, and amoxicillin-clavulanic acid. Antimicrob Agents Chemother 1989; 33: 1901–7

    PubMed  CAS  Google Scholar 

  81. Healy DP, Sahai JV, Sterling LP, et al. Influence of an antacid containing aluminum and magnesium on the pharmacokinetics of Cefixime. Antimicrob Agents Chemother 1989; 33: 1994–7

    PubMed  CAS  Google Scholar 

  82. Blouin RA, Kneer J, Ambros RJ, et al. Influence of antacid and ranitidine on the pharmacokinetics of oral Cefetamet pivoxil. Antimicrob Agents Chemother 1990; 34: 1744–8

    PubMed  CAS  Google Scholar 

  83. Shyu WC, Wilber RB, Pittman KA, et al. Effect of antacid on the bioavailability of cefprozil. Antimicrob Agents Chemother 1992; 36: 962–5

    PubMed  CAS  Google Scholar 

  84. Welling PG, Huang H, Hewitt PF, et al. Bioavailability of erythromycin stearate: influence of food and fluid volume. J Pharm Sci 1978; 67: 764–8

    PubMed  CAS  Google Scholar 

  85. DiSanto AR, Chidos DJ. Influence of study design in assessing food effects on absorption of erythromycin base and erythromycin stearate. Antimicrob Agents Chemother 1981; 20: 190–6

    Google Scholar 

  86. Yamreudeewong W, Scavone JM, Paone RP, et al. Effect of antacid coadministration on the bioavailability of erythromycin stearate. Clin Pharm 1989; 8: 352–354

    PubMed  CAS  Google Scholar 

  87. Boeckh M, Lode H, Hoffken G, et al. Pharmacokinetics of roxithromycin and influence of H2-blockers and antacids on gastrointestinal absorption. Eur J Clin Microbiol Infect Dis 1992; 11: 465–8

    PubMed  CAS  Google Scholar 

  88. Foulds G, Hilligoss DM, Henry EB, et al. The effects of an antacid or Cimetidine on the serum concentrations of azithromycin. J Clin Pharm 1991; 31: 164–7

    CAS  Google Scholar 

  89. Fries JF, Miller SR, Spitz PW, et al. Identification of patients at risk for gastropathy associated with NSAID use. J Rheumatol 1990; 520: 12–9

    Google Scholar 

  90. Neuvonen PJ, Kivisto KT. Effect of magnesium hydroxide on the absorption of tolfenamic and mefenamic acids. Eur J Clin Pharmacol 1988; 35: 495–501

    PubMed  CAS  Google Scholar 

  91. Tanner AR, Caffin JA, Halliday JW, et al. Concurrent administration of antacids and prednisone: effect on serum levels of prednisolone. Br J Clin Pharmacol 1979; 7: 397–400

    PubMed  CAS  Google Scholar 

  92. Uribe M, Casian C, Rojas S, et al. Decreased bioavailability of prednisone due to antacids in patients with chronic active liver disease and in healthy volunteers. Gastroenterology 1981; 80: 661–5

    PubMed  CAS  Google Scholar 

  93. Naggar VF, Khalil SA, Gouda MW. Effect of concomitant administration of magnesium trisilicate on GI absorption of dex-amethasone in humans. J Pharm Sci 1978; 67: 1029–30

    PubMed  CAS  Google Scholar 

  94. Tobert JA, De Schepper PJ, Tjandramaga TB, et al. Effects of antacids on the bioavailability of diflunisal in the fasting and postprandial states. Clin Pharmacol Ther 1981; 30: 385–9

    PubMed  CAS  Google Scholar 

  95. Galeazzi RL. The effect of an antacid on the bioavailability of indomethacin. Eur J Clin Pharmacol 1977; 12: 65–8

    PubMed  CAS  Google Scholar 

  96. Segre EJ, Sevelius H, Varady J, et al. Effects of antacids on naproxen absorption. N Engl J Med 1974; 291: 582–3

    PubMed  CAS  Google Scholar 

  97. Weber SS, Bankhurst AD, Mroszczck E, et al. Effect of mylanta on naproxen bioavailability. Ther Drug Monit 1981; 3: 75–83

    PubMed  CAS  Google Scholar 

  98. Ismail FA, Khalafallah N, Khalil SA, et al. Adsorption of ketoprofen and bumadizone calcium and aluminum-containing antacids and its effect on ketoprofen bioavailability in man. Int J Pharm 1987; 34: 189–96

    CAS  Google Scholar 

  99. Wills RJ, Velagapudi RB, Puri SK, et al. Effect of food and antacid on the absorption of fendosal. Biopharm Drug Dispos 1985; 6: 43–50

    PubMed  CAS  Google Scholar 

  100. Neuvonen PJ. The effect of magnesium hydroxide on the oral absorption of Ibuprofen, ketoprofen and diclofenac. Br J Clin Pharmacol 1991; 31: 263–6

    PubMed  CAS  Google Scholar 

  101. Day RO, Pauli PD, Lam S, et al. The effect of food and various antacids on the absorption of tenoxicam, a new nonsteroidal anti-inflammatory agent. Br J Clin Pharmacol 1987; 24: 323–8

    PubMed  CAS  Google Scholar 

  102. Garnham JC, Kaspi T, Kaye CM, et al. The different effects of sodium bicarbonate and aluminum hydroxide on the absorption of indomethacin in man. Postgrad Med J 1977; 53: 126–9

    PubMed  CAS  Google Scholar 

  103. Emori HW, Paulus H, Bluesone R, et al. Indomethacin serum concentrations in man. Effects of dosage, food and antacid. Ann Rheum Dis 1976; 35: 333–8

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Assistant Professor of Medicine, 2E1.14 Walter Mackenzie Health Sciences Center, University of Alberta, Edmonton, Alberta, T6G 2R7, Canada

    Daniel C. Sadowski

Authors
  1. Daniel C. Sadowski
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Sadowski, D.C. Drug Interactions with Antacids. Drug-Safety 11, 395–407 (1994). https://doi.org/10.2165/00002018-199411060-00002

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00002018-199411060-00002

Keywords

  • Quinidine
  • Antimicrob Agent
  • Tenoxicam
  • Lomefloxacin
  • Magnesium Hydroxide