Sucralfate pp 225-238 | Cite as

Sucralfate Drug Interaction Studies

  • Gilles Caillé
  • Manon Vézina


This section reviews the literature on drug interactions with sucralfate. Since sucralfate is poorly absorbed, most of the dose remains in the gastrointestinal tract and the potential exists for sucralfate to affect the absorption of other drugs. Potential mechanisms of these interactions include adsorption, complexation, decreased dissolution resulting from altered pH, and the formation of a physical barrier to absorption.


Healthy Male Volunteer Roxatidine Acetate Warfarin Concentration Ibuprofen Absorption Erythromycin Ethylsuccinate 
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  1. 1.
    Caldwell JR, Roth SH, Wu WC, et al: Sucralfate treatment of nonsteroidal anti-inflammatory drug-induced gastrointestinal symptoms and mucosal damage. Am J Med 83(suppl 3b):74–82, 1987. The results of this large randomized, placebo-controlled, double-blind trial indicate that sucralfate partially relieves gastrointestinal symptoms and mucosal damage associated with NSAID therapy.PubMedCrossRefGoogle Scholar
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    Stern AI, Ward F, Hartley G: Protective effect of sucralfate against aspirin-induced damage to the human gastric mucosa. Am J Med 83(suppl 3b):83–85, 1987. In this small randomized, placebo-controlled study, it was shown that a single oral dose of sucralfate significantly reduced gastric mucosal damage produced by aspirin probably via the stimulation of local prostaglandin production.PubMedCrossRefGoogle Scholar
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    Lanza F, Peace K, Gustitus L, et al: A blinded endoscopic comparative study of misoprostol versus sucralfate and placebo in the prevention of aspirin-induced gastric and duodenal ulceration. Am J Gastroenterol 83:143–146, 1988. The cytoprotective properties of sucralfate against aspirin-induced damage to the gastric and duodenal mucosae were confirmed in this placebo-controlled, double-blind randomized study where healthy volunteers received 1 g of sucralfate or placebo coadministered with 650 mg of aspirin, four times a day for 7 days.PubMedGoogle Scholar
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    Tesler MA, Lim ES: Protection of gastric mucosa by sucralfate from aspirin-induced erosions. J Clin Gastroenterol 3(suppl 2):175–179, 1981. In this randomized placebo-controlled study, complete protection against aspirin-caused damage to the gastric mucosa was achieved in 8 of 12 subjects whereas 3 other subjects had a partial protection.PubMedGoogle Scholar
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    Harrington SJ, Schlegel JF, Code CF: The protective effect of sucralfate on the gastric mucosa of rats. J Clin Gastroenterol 3(suppl 2):129–134, 1981. The effects of sucralfate on the response of the gastric mucosa to ethanol or taurocholic acid were assessed in rats. The results demonstrate that in the presence of sucralfate, the pH of the gastric contents was higher, the disappearance of H+ was less, and the index of mucosal damage was reduced.PubMedGoogle Scholar
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    Tarnawski A, Hollander D, Krause WJ, et al: Effect of sucralfate on normal gastric mucosa, histologic, ultrastructural and functional assessment. Gastroenterology 84:1331, 1983 (Abstract). This animal study found that sucralfate produces in normal gastric mucosa morphological and functional changes which may account for its therapeutic efficacy.Google Scholar
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    Lau AH, Chang CW, Schlesinger PK: Evaluation of a potential drug interaction between sucralfate and aspirin. Clin Pharmacol Ther 39:151–155, 1986. The results of this randomized crossover study (12 volunteers) reveal that the pharmacokinetic parameters of aspirin were not affected by sucralfate either coadministered with aspirin or given qid for 2 days before aspirin.PubMedCrossRefGoogle Scholar
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    Schneider DK, Gannon RH, Sweeney KR, et al: Influence of sucralfate on trisalicylate bioavailability. J Clin Pharmacol 31:377–379, 1991. This study found that sucralfate does not affect the steady-state bioavailability of trisalicylate absorption. No differences were detected in the pharmacokinetic parameters under study (Cmax, Tmax, and AUC) when sucralfate was administered with trisalicylate compared with trisalicylate alone.PubMedGoogle Scholar
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    Anaya AL, Mayersohn M, Conrad KA, et al: The influence of sucralfate on ibuprofen absorption in healthy adult males. Biopharm Drug Dispos 7:443–451, 1986. In this randomized crossover study on 12 volunteers, sucralfate coadministration with ibuprofen did not alter the extent but did decrease the rate of absorption of the NSAID.PubMedCrossRefGoogle Scholar
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    Caillé G, Du Souich P, Gervais P, et al: Single dose pharmacokinetics of ketoprofen, indomethacin, and naproxen taken alone or with sucralfate. Biopharm Drug Dispos 8:173–183, 1987. The disposition kinetics of ketoprofen, indomethacin, or naproxen with and without sucralfate were studied in a randomized, crossover volunteer trial. The data indicate that sucralfate decreases the rate but not the extent of absorption of all three drugs.PubMedCrossRefGoogle Scholar
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    Kamali F, Fry JR, Smart HL, et al: A double-blind placebo controlled study to examine effects of sucralfate on paracetamol absorption. Br J Clin Pharmacol 19:113–114, 1985. In this double-blind, placebo-controlled crossover study on six volunteers, the concurrent administration of sucralfate did not affect the bioavailability of acetaminophen.PubMedGoogle Scholar
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    DeChristoforo R: Cimetidine—sucralfate: Drug interaction? Hosp Pharm 20:270, 1985 (Letter). In this letter, the author is concerned about the concurrent use of cimetidine and sucralfate. He addresses the issue in terms of preclinical as well as clinical studies investigating such use of both products.Google Scholar
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    Lacz JP, Drees DT, Browne RK: Effects of antacid therapy on the binding of sucralfate to gastric ulcers in the rat. Gastroenterology 84:1220, 1983 (Abstract). These authors determined in a rat model that the administration of cimetidine in doses that produce a pharmacological response did not affect the binding of sucralfate to acetic acid-induced ulcers.Google Scholar
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    Albin H, Vincon G, Lalague MC, et al: Effect of sucralfate on the bioavailability of cimetidine. Eur J Clin Pharmacol 30:493–494, 1986. In this randomized crossover interaction study between cimetidine and sucralfate in 12 human volunteers, sucralfate did not reduce the bioavailability of cimetidine.PubMedCrossRefGoogle Scholar
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    Beck CL, Dietz AJ, Carlson JD, et al: Evaluation of potential cimetidine sucralfate interaction. Clin Pharmacol Ther 41:168, 1987 (Abstract). In this randomized blinded crossover trial conducted in eight healthy male volunteers, coadministration of sucralfate had no significant effect on cimetidine’s pharmacokinetics.Google Scholar
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    Mullersman G, Gotz VP, Russel WL, et al: Lack of clinically significant in vitro and in vivo interactions between ranitidine and sucralfate. J Pharm Sci 75:995–998, 1986. The influence of coadministration of sucralfate on ranitidine bioavailability was evaluated in an in vitro study and in a crossover study in six healthy male volunteers. The in vitro results demonstrate a small extent (≈ 10%) of ranitidine binding to sucralfate paste in the gastrointestinal fluids whereas the pharmacokinetic study showed no diminished ranitidine bioavailability in the presence of sucralfate.PubMedCrossRefGoogle Scholar
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    Maconochie JG, Thomas M, Michael MF, et al: Ranitidine sucralfate interaction study. Clin Pharmacol Ther 41:205, 1987 (Abstract). In a three-period crossover study conducted in 12 healthy male volunteers, coadministration of sucralfate significantly reduced ranitidine’s bioavailability.Google Scholar
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    Parpia SH, Nix DE, Hejmanowski LG, et al: Sucralfate reduces the gastrointestinal absorption of norfloxacin. Antimicrob Agents Chemother 33:99–102, 1989. In a three-period, randomized crossover study of eight healthy male volunteers, 2 hr pre-or concurrent administration of multiple doses of sucralfate significantly reduced gastrointestinal absorption of norfloxacin.PubMedGoogle Scholar
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    Nix DE, Watson WA, Handy L, et al: The effect of sucralfate pretreatment on the pharmacokinetics of ciprofloxacin. Pharmacotherapy 9:377–380, 1989. The influence of sucralfate pretreatment on the pharmacokinetics of ciprofloxacin was evaluated in a randomized crossover study of 12 healthy male volunteers. The results suggest a decrease in ciprofloxacin’s systemic bioavailability on concurrent administration of sucralfate.PubMedGoogle Scholar
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    Mungall D, Talbert RL, Phillips C, et al: Sucralfate and warfarin. Ann Intern Med 98:557, 1983 (Letter to the Editor). A case report of a patient in whom sucralfate appeared to hinder warfarin absorption, resulting in a shortened prothrombin time. Prothrombin time returned to normal on discontinuation of sucralfate.PubMedGoogle Scholar
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    Rey AM, Gums JG: Altered absorption of digoxin, sustained-release quinidine and warfarin with sucralfate administration. DICP Ann Pharmacother 25:745–746, 1991. A clinical case of an elderly woman who displayed subtherapeutic serum concentrations of digoxin, quinidine, and reduced prothrombin time when sucralfate was coadministered.Google Scholar
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    Talbert RL, Dalmady-Israel C, Bussey HI, et al: Effect of sucralfate on plasma warfarin concentration in patients requiring chronic warfarin therapy. Drug Intell Clin Pharm 19:456–457, 1985 (Abstract). The coadministration of sucralfate to five patients on chronic warfarin therapy did not significantly affect prothrombin time, partial thromboplastin time, or plasma warfarin concentration.Google Scholar
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    Neuvonen PJ, Jaakkola A, Totterman J, et al: Clinically significant sucralfate-warfarin interaction is not likely. Br J Clin Pharmacol 20:178–180, 1985 (Letter). In a study of the effect of sucralfate in eight stable warfarin-treated patients, no significant change was found in plasma warfarin concentration or thromboplastin time by the addition of sucralfate.PubMedGoogle Scholar
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    Giesing DJ, Lanman RC, Dimmitt DC, et al: Lack of effect of sucralfate on digoxin pharmacokinetics. Gastroenterology 84:1165, 1983 (Abstract). Coadministration of digoxin and sucralfate in 12 normal volunteers resulted in a nonsignificant decrease in the AUC and urinary excretion of digoxin. These differences were not observed when the doses of the two drugs were staggered.Google Scholar
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    Turkistani AAA, Gaber M, Al-Meshal MA, et al: Effect of sucralfate on procainamide absorption. Int J Pharm 59:R1–R3, 1990 (Rapid Communication). In this crossover study of four healthy male volunteers, procainamide absorption was not significantly altered by coadministration of sucralfate. Procainamide concentrations were assessed by the volunteer’s saliva.CrossRefGoogle Scholar
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    Ryan R, Carlson J, Farris F: Effect of sucralfate in the absorption and disposition of amitriptyline in humans. Fed Proc 45(3):205, 1986 (Abstract 299). Blinded crossover study of six healthy male volunteers indicating that sucralfate does not modify the absorption parameters (C max, T max) but does increase the elimination of amitriptyline.Google Scholar
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    Letendre PW, Carlson JD, Seifert RD, et al: Effect of sucralfate on the absorption and pharmaco-kinetics of chlorpropamide. J Clin Pharmacol 26:622–625, 1986. In this two-way randomized, crossover study of 12 healthy male volunteers, pretreatment followed by simultaneous administration of sucralfate had no significant effect on absorption and bioavailability of chlorpropamide.PubMedGoogle Scholar
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    Miller LG, Prichard JG, White CA, et al: Effect of concurrent sucralfate administration on the absorption of erythromycin. J Clin Pharmacol 30:39–44, 1990. The possible effect of coadministration of sucralfate on absorption and bioavailability of erythromycin was evaluated in this open label single-dose study of six healthy volunteers. Coadministration of sucralfate did not significantly alter the above-mentioned parameters.PubMedGoogle Scholar
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    Goss TF, Piscitelli SC, Schentag IJ: Evaluation of ketoconazole bioavailability interactions with sucralfate and ranitidine using gastric pH monitoring. Clin Pharmacol Ther 49:128, 1991 (Abstract). The effects of sucralfate and ranitidine on ketoconazole bioavailability were evaluated in this three-period, randomized, crossover study performed in six healthy male volunteers. A significant decrease of ketoconazole bioavailability was reported on coadministration of ranitidine and was related to an elevated gastric pH, whereas the moderate decrease seen with simultaneous sucralfate administration was not linked to an altered gastric pH.Google Scholar
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    Hall TG, Cuddy PG, Glass CJ, et al: Effect of sucralfate on phenytoin bioavailability. Drug Intell Clin Pharm 20:607–611, 1986. The potential effect of coadministration of sucralfate on phenytoin’s bioavailability was examined in this open, crossover study of nine healthy male volunteers. Although the results suggest that simultaneous sucralfate administration affects phenytoin’s absorption, the difference was not significant.PubMedGoogle Scholar
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    Gambertoglio JG, Romae DR, Yong CL, et al: Lack of effect of sucralfate on prednisone bioavailability. Am J Gastroenterol 82:42–45, 1987. Randomized three-way crossover study in 12 healthy volunteers showing that sucralfate does not have a clinically significant effect on the bioavailability of prednisone.PubMedGoogle Scholar
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    Gouda MW, Hikal AH, Babhair SA, et al: Effect of sucralfate and antacids on the bioavailability of sulpride in humans. Int J Pharm 22:257–263, 1984. The effect of coadministration of either sucralfate or an antacid on sulpride’s bioavailability was determined in this crossover study of six healthy male volunteers. Both sucralfate and the antacid significantly reduced sulpride’s oral bioavailability. The bioavailability was also reduced in two volunteers on administration of the two agents 2 hr prior, whereas no significant alteration was seen in one volunteer when the agents were administered 2 hr after sulpride.CrossRefGoogle Scholar
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    Cantral KA, Schaaf LJ, Jungnickel PW, et al: Effect of sucralfate on theophylline absorption in healthy volunteers. Clin Pharm 7:58–61, 1988. In this two-way, randomized crossover study of eight healthy male volunteers, the rate or completeness of theophylline’s absorption was not clinically altered on simultaneous administration of multiple doses of sucralfate.PubMedGoogle Scholar
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Copyright information

© Plenum Press 1995

Authors and Affiliations

  • Gilles Caillé
    • 1
  • Manon Vézina
    • 2
  1. 1.Département de Pharmacologie, Faculté de MédecineUniversité de MontréalCanada
  2. 2.Département de Pharmacologie, Faculté de MédecineUniversité de Montréal, and Centre de Recherche Fernand Seguin, Hôpital Louis-HippolyteLafontaineCanada

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