ATC Class:A02BX02
VA Class:GA302
Sucralfate, an anionic sulfated disaccharide, is an inhibitor of pepsin and an antiulcer agent that binds to the surface of ulcers, forming a protective barrier.
Sucralfate is used in the short-term (up to 8 weeks) treatment of duodenal ulcer. Antacids may be used as adjuncts to sucralfate therapy to relieve pain, but should not be taken within 30 minutes before or after administration of sucralfate.
In controlled studies in patients with duodenal ulcer who were receiving supplemental antacids, reported rates of ulcer healing for sucralfate (3 or 4 g daily as tablets) vs placebo were: 33-39% vs 13-25% at 2 weeks, 69-92% vs 41-64% at 4 weeks, 60% vs 24% at 6 weeks, and 77-86% vs 41% at 12 weeks. Sucralfate also produced greater reductions in severity and occurrence of daytime and nocturnal pain and in antacid consumption than did placebo. In a multicenter, double-blind, controlled study in patients with duodenal ulcer, ulcer healing rates with sucralfate 1 g 4 times daily (as the suspension) versus placebo were: 16 vs 7% at 2 weeks, 46 vs 27% at 4 weeks, and 66 vs 39% at 8 weeks, respectively. The manufactuer states that equivalence of sucralfate suspension and tablets has not been demonstrated.
In a limited number of well-controlled studies comparing 4-12 weeks of oral therapy with 4 g of sucralfate daily to that with 1-1.2 g of cimetidine daily, 87-100% of sucralfate-treated and 83-86% of cimetidine-treated duodenal ulcers were healed as evidenced by endoscopic examination. Based on these limited studies, it appears that the short-term effect of sucralfate on duodenal ulcer healing is comparable to that of cimetidine. In one study, follow-up of sucralfate- and cimetidine-treated patients revealed that the cumulative relapse rate after 1 year was similar in both treatment groups; however, the average duration of remission in patients who developed a recurrence was longer in patients initially treated with sucralfate (7.3 months) than in those initially treated with cimetidine (4.6 months).
In one controlled study comparing 8 weeks of oral therapy with 4 g of sucralfate daily to that with 8 aluminum hydroxide and magnesium trisilicate antacid tablets daily (strength unknown), 93% of sucralfate-treated and 31% of antacid-treated duodenal ulcers were healed. Current epidemiologic and clinical evidence supports a strong association between gastric infection with Helicobacter pylori and the pathogenesis of duodenal and gastric ulcers;100, 101, 108, 121, 132, 133, 136, 140, 142, 144, 145, 146, 150, 151, 152, 153, 154, 155 long-term H. pylori infection also has been implicated as a risk factor for gastric cancer.101, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 121, 132, 140 For additional information on the association of this infection with these and other GI conditions, see Helicobacter pylori Infection, under Uses, in Clarithromycin 8:12.12.92.
Conventional antiulcer therapy with H2-receptor antagonists, proton-pump inhibitors, sucralfate, and/or antacids heals ulcers but generally is ineffective in eradicating H. pylori , and such therapy is associated with a high rate of ulcer recurrence (e.g., 60-100% per year).100, 132, 136, 140, 144, 146, 154 The American College of Gastroenterology (ACG), the National Institutes of Health (NIH), and most clinicians currently recommend that all patients with initial or recurrent duodenal or gastric ulcer and documented H. pylori infection receive anti-infective therapy for treatment of the infection.128, 132, 144, 145, 146 Although 3-drug regimens consisting of a bismuth salt (e.g., bismuth subsalicylate) and 2 anti-infective agents (e.g., tetracycline or amoxicillin plus metronidazole) administered for 10-14 days have been effective in eradicating the infection, resolving associated gastritis, healing peptic ulcer, and preventing ulcer recurrence in many patients with H. pylori -associated peptic ulcer disease,100, 101, 102, 118, 121, 123, 132, 133, 134, 135, 139, 140, 142, 143, 144, 145, 146, 147, 153, 155, 159, 163, 164, 165 current evidence principally from studies in Europe suggests that 1 week of such therapy provides comparable H. pylori eradication rates.132, 145, 146 Other regimens that combine one or more anti-infective agents (e.g., clarithromycin, amoxicillin) with a bismuth salt and/or an antisecretory agent (e.g., omeprazole, lansoprazole, H2-receptor antagonist) also have been used successfully for H. pylori eradication,100, 101, 102, 103, 104, 105, 106, 107, 118, 119, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 140, 144, 145, 146, 167, 168, 169, 170, 171 and the choice of a particular regimen should be based on the rapidly evolving data on optimal therapy, including consideration of the patient's prior exposure to anti-infective agents, the local prevalence of resistance, patient compliance, and costs of therapy.128, 132, 140, 145, 165, 166
Current evidence suggests that inclusion of a proton-pump inhibitor (e.g., omeprazole, lansoprazole) in anti- H. pylori regimens containing 2 anti-infectives enhances effectiveness, and limited data suggest that such regimens retain good efficacy despite imidazole (e.g., metronidazole) resistance.132, 145, 167 Therefore, the ACG and many clinicians132, 147, 148 currently recommend 1 week of therapy with a proton-pump inhibitor and 2 anti-infective agents (usually clarithromycin and amoxicillin or metronidazole), or a 3-drug, bismuth-based regimen (e.g., bismuth-metronidazole-tetracycline) concomitantly with a proton-pump inhibitor, for treatment of H. pylori infection.129, 132, 145, 148 For a more complete discussion of H. pylori infection, including details about the efficacy of various regimens and rationale for drug selection, see Helicobacter pylori Infection, under Uses, in Clarithromycin 8:12.12.92.
Sucralfate is used in reduced dosage as maintenance therapy following healing of active duodenal ulcer to reduce ulcer recurrence. In placebo-controlled studies, duodenal ulcer recurrence (as evidenced by endoscopic examination) rates at 4 months, 6 months, 8 months, and 1 year were 8-42, 19-33, and 27-42%, respectively, for 1 g of sucralfate twice daily versus 38-63, 50-69, and 65-81%, respectively, for placebo. In other studies, recurrence rates for up to 1 year of sucralfate maintenance therapy (2 g daily) were similar to those observed after up to 1 year of cimetidine maintenance therapy (400 mg at bedtime daily).
Sucralfate has been used in the treatment of patients with gastric ulcer†, but its efficacy in this condition has not been established. In a limited number of patients in controlled studies, sucralfate was more effective than placebo in healing gastric ulcer. Sucralfate also relieved ulcer-related pain more rapidly than did placebo in patients with gastric ulcer. Based on preliminary data, it had appeared that maintenance administration of sucralfate did not affect the rate of recurrence of gastric ulcer; however, in a limited number of placebo-controlled studies of up to 1 year's duration in patients with healed gastric ulcer, daily maintenance administration of 2-3 of sucralfate reduced the rate of gastric ulcer recurrence.
Sucralfate appears to be as effective as cimetidine in the short-term treatment of gastric ulcer†. In a limited number of controlled studies, there was no difference in ulcer healing, symptomatic relief, or antacid consumption between sucralfate- and cimetidine-treated patients.
In one poorly designed study comparing sucralfate and an aluminum hydroxide liquid antacid in patients with gastric ulcer†, healing in patients treated with sucralfate was reported to be faster than that in patients treated with aluminum hydroxide; however, patients in this study used only 20 mL of an aluminum hydroxide antacid (concentration unknown) 3 times daily.
Current epidemiologic and clinical evidence supports a strong association between gastric infection with H. pylori and the pathogenesis of duodenal and gastric ulcers,100, 101, 108, 121, 132, 133, 136, 140, 142, 144, 145, 146, 150, 151, 152, 153, 154, 155 and the ACG, NIH, and most clinicians currently recommend that all patients with initial or recurrent duodenal or gastric ulcer and documented H. pylori infection receive anti-infective therapy for treatment of the infection.128, 132, 144, 145, 146 The choice of a particular regimen should be based on the rapidly evolving data on optimal therapy, including consideration of the patient's prior exposure to anti-infective agents, the local prevalence of resistance, patient compliance, and costs of therapy.100, 101, 102, 103, 104, 105, 118, 119, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 140, 144, 145, 146, 148 (See Duodenal Ulcer: Acute Therapy, in Uses.) For a more complete discussion of H. pylori infection, including details about the efficacy of various regimens and rationale for drug selection, see Helicobacter pylori Infection, under Uses, in Clarithromycin 8:12.12.92.
Sucralfate has been shown to protect the gastric mucosa from aspirin-induced erosions†. In one study in healthy adults receiving 3.6 g of aspirin daily, sucralfate (4 g daily) provided complete protection against aspirin-induced mucosal injury (as evidenced by endoscopic examination) in approximately 70% of individuals. Further study is needed to confirm these preliminary findings and to determine the safety and efficacy of sucralfate in the prevention of aspirin-induced gastric erosions.
Sucralfate has been used as an oral suspension† for the prevention and treatment of chemotherapy-induced mucositis†, 100, 101, 102, 103, 104, 108 but results have been conflicting101 and additional study is necessary.100, 104, 106, 107 Although it has been suggested that sucralfate oral suspensions may have a potential beneficial effect in reducing pathogenic gastric microbial colonization in these and other (e.g., intubated) patients,101, 102 some clinicians have questioned current findings supporting this suggestion.106, 107
Sucralfate is administered orally. The drug should be taken on an empty stomach, 1 hour before each meal and at bedtime. Antacids may be used as needed for relief of pain but should not be taken within 30 minutes before or after sucralfate.
For the treatment of active duodenal ulcer, the usual adult dosage of sucralfate is 1 g 4 times daily. Although healing of the ulcer may occur during the first or second week of therapy, treatment should be continued for 4-8 weeks unless healing has been shown by radiographic or endoscopic examination.
For maintenance therapy following healing of acute duodenal ulcer to reduce ulcer recurrence, the usual adult dosage of sucralfate is 1 g twice daily.
For the treatment of gastric ulcer†, a sucralfate dosage of 1 g 4 times daily has been used in adults.
Sucralfate is generally well tolerated. The most frequent adverse effect of sucralfate is constipation, which reportedly occurs in about 2% of patients receiving the drug. Other adverse effects of sucralfate reportedly occur in less than 1% of patients and include diarrhea, nausea, vomiting, gastric discomfort, flatulence, indigestion, dry mouth, rash, pruritus, back pain, headache, dizziness, insomnia, sleepiness, and vertigo. Adverse reactions requiring discontinuance of the drug occur rarely. In postmarketing experience, hypersensitivity reactions such as urticaria (hives), angioedema, respiratory difficulty, and rhinitis have been reported with sucralfate tablets. Similar reactions have been reported with sucralfate suspension. In addition, laryngospasm and facial swelling have been reported with sucralfate suspension, but a causal relationship has not been established.
Bezoars have been reported with sucralfate therapy. Most patients who developed bezoars had underlying medical conditions that may have predisposed to bezoar formation (e.g., delayed gastric emplying) or were receiving concomitant enteral tube feedings.
Precautions and Contraindications
Since duodenal ulcer is a chronic recurrent disease, successful therapy with sucralfate should not be expected to alter the post-healing frequency of recurrence or the severity of duodenal ulceration.
Small amounts of aluminum are absorbed from the GI tract when sucralfate is administered orally. Concomitant use of sucralfate with other products that contain aluminum (e.g., aluminum-containing antacids) also can increase the total body burden of aluminum. In patients with normal renal function, this increased body burden of aluminum is excreted in the urine; however, patients with chronic renal failure or those receiving dialysis treatment may not adequately excrete the absorbed aluminum. In addition, because the absorbed aluminum is bound to plasma proteins (e.g., albumin, transferrin) and is not dialyzable, accumulation and intoxication (e.g., aluminum osteodystrophy, osteomalacia, encephalopathy) can occur in patients with impaired renal function. Therefore, sucralfate should be used with caution in patients with chronic renal failure.109
Inadvertent injection of sucralfate suspension, which is insoluble and has insoluble excipients, has led to fatal complications, including pulmonary and cerebral emboli. Sucralfate suspension is not intended for IV administration.
Safety and efficacy of sucralfate in children have not been established.
Mutagenicity and Carcinogenicity
Mutagenicity studies have not been conducted with sucralfate to date. No evidence of carcinogenesis was seen in animals receiving oral sucralfate dosages up to 1 g/kg daily (12 times the usual human dosage) for 24 months.
Pregnancy, Fertility, and Lactation
Reproduction studies in mice, rats, and rabbits using sucralfate dosages up to 50 times the usual human dosage have not revealed evidence of harm to the fetus. There are no adequate and controlled studies to date using sucralfate in pregnant women, and the drug should be used during pregnancy only when clearly needed.
The effect of sucralfate on fertility in humans is not known. A reproduction study in rats using sucralfate dosages up to 38 times the usual human dosage did not reveal evidence of impaired fertility.
Since it is not known if sucralfate is distributed into milk, the drug should be used with caution in nursing women.
Studies in animals and healthy individuals have shown that concomitant administration of sucralfate with cimetidine, digoxin, ketoconazole, phenytoin, ranitidine, tetracycline, or theophylline results in a reduction in bioavailability of these drugs. These interactions appear to be nonsystemic in origin, apparently resulting from binding of these agents to sucralfate in the GI tract. Although subtherapeutic prothrombin times with concomitant sucralfate and warfarin administration also have been reported, initiation of sucralfate in patients maintained on warfarin therapy reportedly did not alter serum warfarin concentrations or prothrombin times in at least 2 clinical studies. Although the clinical importance of these findings has not been determined in humans, it has been suggested that sucralfate be given 2 hours before or after any of these drugs. Because of the potential of sucralfate to alter the absorption of some drugs from the GI tract, separate administration of sucralfate and other drugs should be considered during concomitant therapy when alterations in bioavailability of the other drug(s) are believed to be critical.
Concomitant sucralfate, presumably because of its aluminum content, decreases GI absorption of ciprofloxacin and norfloxacin and may result in substantial (e.g., 50% or greater) decreases in serum concentrations of the anti-infectives.110, 111, 112, 113, 114 Patients should be instructed not to ingest sucralfate concomitantly with, or within 2 hours of, a ciprofloxacin or norfloxacin dose.111, 113, 114
Limited information is available on the acute toxicity of sucralfate. No serious toxicity was seen in healthy adults following oral administration of a single 12-g dose of sucralfate. Acute oral toxicity studies in animals using sucralfate doses up to 12 g/kg could not establish a lethal dose. The manufacturer states that the risks associated with sucralfate overdosage in humans should be minimal. Aluminum toxicity occurred in at least one patient with end-stage renal disease who was receiving sucralfate; it was suspected that the toxicity resulted from systemic absorption of aluminum released during dissociation of the drug in the GI tract.109
The exact mechanism(s) of action of sucralfate in peptic ulcer disease is unclear, but the therapeutic effects of the drug have been shown to result from local (i.e., at the ulcer site) rather than systemic activity.
Sucralfate does not appreciably affect gastric acid output or concentration.
Following oral administration, sucralfate rapidly reacts with hydrochloric acid in the stomach to form a highly condensed, viscous, adhesive, paste-like substance with the capacity to buffer acid (14-16 mEq of in vitro acid-neutralizing capacity per 1-g dose); the drug persists in this form in the more alkaline environment of the proximal duodenum. Sucralfate does not appreciably neutralize the acidity of gastric contents because its in vitro rate of acid neutralization is very slow (about 25% the rate of an aluminum and magnesium hydroxides antacid). In vitro, only about 10% of the potential neutralizing capacity of sucralfate is consumed upon addition of hydrochloric acid. The paste-like substance formed when the drug reacts with hydrochloric acid appears to be resistant to further reaction with acid. Data from in vitro and clinical studies have shown that therapeutic doses of sucralfate do not have an antacid effect; however, since sucralfate adheres to the gastroduodenal mucosa, its acid-neutralizing effect may be important for the local protection of the ulcer. (See Pharmacology: Protection of the Ulcer Site.)
Sucralfate binds to the surface of both gastric and duodenal ulcers. The drug has greater affinity for the ulcer site than for normal GI mucosa; however, binding to normal mucosa does occur. In one study in patients receiving sucralfate prior to gastric resection, the concentrations of sucralfate at gastric ulcer sites were 6-7 times greater than those at normal gastric mucosa. Based on limited data from animal studies, sucralfate appears to exhibit a greater affinity for duodenal ulcers than gastric ulcers; however, further study is needed to confirm this finding. Sucralfate also binds to acute gastric erosions produced by alcohol or other drugs (e.g., aspirin).
As sucralfate reacts with hydrochloric acid in the stomach, its 8 salts gradually dissociate to release aluminum ions; highly polar polyanions composed of sucrose sulfate with some remaining aluminum groups are formed during the reaction. The insolubility and high polarity of these anions are probably responsible for sucralfate's poor absorption from the GI tract. A major portion of a dose of sucralfate binds electrostatically to positively charged protein molecules in the damaged mucosa of the GI tract to form insoluble, stable complexes, and only a small amount actually dissociates in the GI contents. The insoluble complexes form an adherent, protective barrier at the ulcer site.
The barrier formed at the ulcer site by sucralfate protects the ulcer from the potential ulcerogenic properties of pepsin, acid, and bile, thus allowing the ulcer to heal.
The barrier inhibits pepsin's proteolytic effect by preventing pepsin from binding with proteinaceous substrates (e.g., albumin, fibrinogen) present at the ulcer surface. In addition to forming a barrier to pepsin diffusion, sucralfate has been shown to inhibit the activity of pepsin in vitro, by adsorbing pepsin. In one uncontrolled study in patients with peptic ulcer disease, sucralfate reduced pepsin activity in gastric secretions by 32-55% within 30 minutes following single, 1- to 3-g oral doses.
Sucralfate has been shown to provide a barrier against back-diffusion of hydrogen ions by directly interacting with acid at the surface of the ulcer; the sucralfate layer exhibits a local, acid-neutralizing effect. Sucralfate has also been shown to adsorb bile acids in vitro and thus reduce their concentration; the maximum amount of bile acids adsorbed was approximately 112 mg/g of sucralfate. Sucralfate inhibits back-diffusion of glycocholic acid and protects against gastric mucosal damage produced by taurocholic acid. The importance of sucralfate's effects on bile acids in the treatment of peptic ulcer disease is unclear; however, there is a positive association between gastric concentrations of bile acids and gastric ulcers.
Sucralfate may decrease the rate of gastric emptying. Following oral administration of a single 1-g dose in one study in healthy adults, sucralfate caused an increase in mean gastric emptying time; however, this increase was not considered clinically important. The effect of sucralfate on gastric emptying time in animals has been conflicting; however, following oral administration of single doses of 50 mg/kg in animals in one study, sucralfate did not appreciably affect gastric emptying time, and oral doses of sucralfate up to 400 mg/kg had no effect on peristalsis in these animals.
Sucralfate does not affect the activity of trypsin or pancreatic amylase.
Sucralfate has little, if any, effect on blood coagulation. No change in PTs or PTTs was observed in patients receiving the drug during clinical trials.
Preliminary studies in animals showed sucralfate to be only minimally absorbed following oral administration; thus, extensive pharmacokinetic evaluation of the drug in humans has not been conducted.
Sucralfate is only minimally absorbed from the GI tract following oral administration; the drug is absorbed as sucrose sulfate. (See Pharmacokinetics: Elimination.) Poor absorption may result from the high polarity and low solubility of the drug in the GI tract. Studies in animals indicate that only 3-5% of an oral dose of sucralfate reaches systemic circulation as sucrose sulfate. Following oral administration of multiple doses of the drug (200 mg/kg daily) in animals, sucrose sulfate did not accumulate in plasma.
Since sucralfate exerts its therapeutic effects directly at the site of the ulcer, the duration of action depends on the time that the drug is in contact with this site. The drug's viscous adhesiveness, slow reaction with acid, and high affinity for damaged mucosa contribute to its prolonged action. Binding to the ulcer site has been shown for up to 6 hours following oral administration, and 30% of the dose is retained within the GI tract for at least 3 hours.
Distribution of sucralfate into human body tissues and fluids following systemic absorption has not been determined. The apparent volume of distribution of sucrose sulfate has been determined in animals and is reported to be approximately 20% of body weight. Following oral administration of sucralfate in animals, the drug is only minimally distributed into tissues. Approximately 95% of the dose remains in the GI tract, with only small amounts being distributed into liver, kidneys, skeletal muscle, adipose tissue, and skin.
It is not known if sucralfate crosses the placenta or is distributed into milk.
Following IV administration of sucrose sulfate, plasma concentrations decline rapidly and show first-order elimination. In animals, the elimination half-life of sucrose sulfate ranges from 6-20 hours.
Sucrose sulfate is formed in the GI tract following reaction of sucralfate with hydrochloric acid. (See Pharmacology: Binding to the Ulcer Site.) Sucrose sulfate is not metabolized. In animals, more than 90% of an orally administered dose of sucrose sulfate is excreted unchanged in feces within 48 hours. The small amount (3-5%) of sucralfate that is absorbed as sucrose sulfate is excreted unchanged in urine within 48 hours.
Sucralfate, an anionic, sulfated disaccharide, is an inhibitor of pepsin and an antiulcer agent. The drug is a basic, aluminum complex of sucrose sulfate. Sucralfate is structurally related to heparin but lacks anticoagulant activity. Sucralfate is also structurally related to sodium amylosulfate and chondroitin sulfate, but unlike these anionic sulfated polysaccharides, sucralfate is a pure disaccharide derivative. Although structurally related to sucrose, sucralfate is not utilized as a sugar in vivo in humans.
Sucralfate exhibits greater stability at the glycoside linkage than do most disaccharides or polysaccharides, apparently because of the presence of sulfate groups in sucralfate. Each of the 8 alcoholic hydroxyl groups of the disaccharide molecule are sulfated to yield sucrose octasulfate, and each of the sulfate ester anions forms a salt with an aluminum hydroxide group. Hydrogen bonds between hydroxyl groups and water molecules produce intramolecular and intermolecular bridges, forming a polymer.
Sucralfate occurs as a white, amorphous powder and is practically insoluble in water and in alcohol and soluble in strong acids and in alkalis.
Commercially available sucralfate tablets should be stored in tight containers at room temperature and are stable for 2 years after manufacture. The commercially available suspension of sucralfate should be stored at 15-30°C; freezing of the suspension should be avoided.
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.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Oral | Suspension | 500 mg/5 mL | ||
Tablets | 1 g* | Carafate® (scored) | Axcan | |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
100. Ateshkadi A, Lam NP, Johnson CA. Helicobacter pylori and peptic ulcer disease. Clin Pharm . 1993; 12:34-48. [PubMed 8428432]
101. Blaser MJ. Helicobacter pylori: its role in disease. Clin Infect . 1992; 15:386-91.
102. Marshall BJ. Treatment strategies for Helicobacter pylori infection. Gastroenterol Clin North Am . 1993; 22:183-98. [PubMed 8449566]
103. Bayerdorffer E, Mannes GA, Sommer A et al. Long-term follow-up after eradication of Helicobacter pylori with a combination of omeprazole and amoxycillin. Scand J Gastroenterol Suppl . 1993; 196:19-25. [PubMed 8341987]
104. Unge P, Ekstrom P. Effects of combination therapy with omeprazole and an antibiotic on H. pylori and duodenal ulcer disease. Scand J Gastroenterol Suppl . 1993; 196:17-8.
105. Hunt RH. Hp and pH: implications for the eradication of Helicobacter pylori. Scand J Gastroenterol Suppl . 1993; 196:12-6. [PubMed 8341986]
106. Malfertheiner P. Compliance, adverse events and antibiotic resistance in Helicobacter pylori treatment. Scand J Gastroenterol Suppl . 1993; 196:34-7. [PubMed 8341989]
107. Bell GD, Powell U. Eradication of Helicobacter pylori and its effect in peptic ulcer disease. Scand J Gastroenterol Suppl . 1993; 196:7-11. [PubMed 8341990]
108. Farrell MK. Dr. Apley meets Helicobacter pylori. J Pediatr Gastroenterol Nutr . 1993; 16:118-9. [PubMed 8450375]
109. Nomura A, Stemmermann GN, Chyou PH et al. Helicobacter pylori infection and gastric carcinoma among Japanese Americans in Hawaii. N Engl J Med . 1991; 325:1132-6. [PubMed 1891021]
110. Parsonnet J, Friedman GD, Vandersteen DP et al. Helicobacter pylori infection and the risk of gastric carcinoma. N Engl J Med . 1991; 325:1127-31. [PubMed 1891020]
111. The EUROGAST Study Group. An international association between Helicobacter pylori infection and gastric cancer. Lancet . 1993; 341:1359-62. [PubMed 8098787]
112. Talley NJ, Zinsmeister AR, Weaver A et al. Gastric adenocarcinoma and Helicobacter pylori infection. J Natl Cancer Inst . 1991; 83:1734-9. [PubMed 1770552]
113. Forman D, Newell DG, Fullerton F et al. Association between infection with Helicobacter pylori and risk of gastric cancer: evidence from a prospective investigation. BMJ . 1991; 302:1302-5. [PubMedCentral][PubMed 2059685]
114. Forman D. Helicobacter pylori infection: a novel risk factor in the etiology of gastric cancer. J Natl Cancer Inst . 1991; 83:1702-3. [PubMed 1770545]
115. Parsonnet J. Helicobacter pylori and gastric cancer. Gastroenterol Clin North Am . 1993; 22:89-104. [PubMed 8449573]
116. Correa P. Is gastric carcinoma an infectious disease? N Engl J Med . 1991; 325:1170-1.
117. Isaacson PG, Spencer J. Is gastric lymphoma an infectious disease? Hum Pathol . 1993; 24:569-70.
118. Rauws EAJ, Tytgat GNJ. Cure of duodenal ulcer with eradication of Helicobacter pylori. Lancet . 1990; 335:1233-5. [PubMed 1971318]
119. Hunt RH. pH and Hp—gastric acid secretion and Helicobacter pylori: implications for ulcer healing and eradication of the organism. Am J Gastroenterol . 1993; 88:481-3. [PubMed 8470623]
120. Reviewers' comments (personal observations) on Helicobacter pylori ; 1993 Oct 26.
121. Marshall BJ. Helicobacter pylori . Am J Gastroenterol . 1994; 89(Suppl):S116-28.
122. Labenz J, Gyenes E, Rühl GH et al. Amoxicillin plus omeprazole versus triple therapy for eradication of Helicobacter pylori in duodenal ulcer disease: a prospective, randomized, and controlled study. Gut . 1993; 34:1167-70. [PubMedCentral][PubMed 8406147]
123. Anon. Drugs for treatment of peptic ulcers. Med Lett Drugs Ther . 1994; 36:65-7. [PubMed 7912812]
124. Freston JW. Emerging strategies for managing peptic ulcer disease. Scand J Gastroenterol Suppl . 1994; 201:49-54. [PubMed 8047824]
125. Axon ATR. The role of acid inhibition in the treatment of Helicobacter pylori infection. Scand J Gastroenterol Suppl . 1994; 201:16-23. [PubMed 8047818]
126. Labenz J, Rühl GH, Bertrams J et al. Medium- or high-dose omeprazole plus amoxicillin eradicates Helicobacter pylori in gastric ulcer disease. Am J Gastroenterol . 1994; 89:726-30. [PubMed 8172146]
127. Labenz J, Borsch G. Evidence for the essential role of Helicobacter pylori in gastric ulcer disease. Gut . 1994; 35:19-22. [PubMedCentral][PubMed 8307443]
128. NIH Consensus Development Panel on Helicobacter pylori in Peptic Ulcer Disease. Helicobacter pylori in peptic ulcer disease. JAMA . 1994; 272:65-9. [PubMed 8007082]
129. Fennerty MB. Helicobacter pylori . Ann Intern Med . 1994: 154;721-7.
130. Adamek RJ, Wegener M, Labenz J et al. Medium-term results of oral and intravenous omeprazole/amoxicillin Helicobacter pylori eradication therapy. Am J Gastroenterol . 1994; 89:39-42. [PubMed 8273795]
131. Markham A, McTavish D. Clarithromycin and omeprazole: as Helicobacter pylori eradication therapy in patients with H. pylori-associated gastric disorders. Drugs . 1996; 51:161-78. [PubMed 8741237]
132. Soll AH. Medical treatment of peptic ulcer disease. JAMA . 1996; 275:622-9. [PubMed 8594244]
133. Murray DM, DuPont HL, Cooperstock M et al. Evaluation of new anti-infective drugs for the treatment of gastritis and peptic ulcer disease associated with infection by Helicobacter pylori. Clin Infect Dis . 1992; 15(Suppl 1):S268-73.
134. Chiba N, Rao BV, Rademaker JW et al. Meta-analysis of the efficacy of antibiotic therapy in eradicating Helicobacter pylori. Am J Gastroenterol . 1992; 87:1716-27. [PubMed 1449132]
135. Glassman MS. Helicobacter pylori infection in children. A clinical overview. Clin Pediatr (Phila) . 1992; 31:481-7. [PubMed 1643767]
136. Peterson WL. Helicobacter pylori and peptic ulcer disease. N Engl J Med . 1991; 324:1043-8. [PubMed 2005942]
137. Logan RP, Gummett PA, Misiewicz JJ et al. One week eradication regimen for Helicobacter pylori . Lancet . 1991; 338:1249-52. [PubMed 1682653]
138. Burette A, Glupczynski Y. On: The who's and when's of therapy for Helicobacter pylori . 1991; 86:924-5. Letter.
139. Bianchi Porro G, Parente F, Lazzaroni M. Short and long term outcome of Helicobacter pylori positive resistant duodenal ulcers treated with colloidal bismuth subcitrate plus antibiotics or sucralfate alone. Gut . 1993; 34:466-9. [PubMedCentral][PubMed 8491391]
140. Reviewers' comments (personal observations) on the Aminopenicillins General Statement 8:12.16.
141. Bell GD, Powell KU, Burridge SM et al. Helicobacter pylori eradication: efficacy and side effect profile of a combination of omeprazole, amoxycillin and metronidazole compared with four alternative regimens. Q J Med . 1993; 86:743-50. [PubMed 8265776]
142. Labenz J, Börsch G. Highly significant change of the clinical course of relapsing and complicated peptic ulcer disease after cure of Helicobacter pylori infection. Am J Gastroenterol . 1994; 89:1785-8. [PubMed 7942667]
143. Wang WM, Chen CY, Jan CM et al. Long-term follow-up and serological study after triple therapy of Helicobacter pylori -associated duodenal ulcer. Am J Gastroenterol . 1994; 89:1793-6. [PubMed 7942669]
144. Walsh JH, Peterson WL. The treatment of Helicobacter pylori infection in the management of peptic ulcer disease. N Engl J Med . 1995; 333:984-91. [PubMed 7666920]
145. Hackelsberger A, Malfertheiner P. A risk-benefit assessment of drugs used in the eradication of Helicobacter pylori infection. Drug Saf . 1996; 15:30-52. [PubMed 8862962]
146. Rauws EAJ, van der Hulst RWM. Current guidelines for the eradication of Helicobacter pylori in peptic ulcer disease. Drugs . 1995; 6:984-90.
147. van der Hulst RWM, Keller JJ, Rauws EAJ et al. Treatment of Helicobacter pylori infection: a review of the world literature. Helicobacter . 1996; 1:6-19. [PubMed 9398908]
148. Lind T, Veldhuyzen van Zanten S, Unge P et al. Eradication of Helicobacter pylori using one-week triple therapies combining omeprazole with two antimicrobials: the MACH I study. Helicobacter . 1996; 1:138-44. [PubMed 9398894]
149. Anon. The choice of antibacterial drugs. Med Lett Drugs Ther . 1996; 38:25-34. [PubMed 8598824]
150. Graham DY, Go MF. Evaluation of new antiinfective drugs for Helicobacter pylori infection: revisited and updated. Clin Infect Dis . 1993; 17:293-4. [PubMed 8399892]
151. Murray DM, DuPont HL. Evaluation of new antiinfective drugs for Helicobacter pylori infection: revisited and updated. Clin Infect Dis . 1993; 17:294-5.
152. George LL, Borody TJ, Andrews P et al. Cure of duodenal ulcer after eradication of H. pylori. Med J Aust . 1990; 153:145-9. [PubMed 1974027]
153. Fiocca R, Solcia E, Santoro B. Duodenal ulcer relapse after eradication of Helicobacter pylori. Lancet . 1991; 337:1614. [PubMed 1675746]
154. Marshall BJ. Campylobacter pylori: its link to gastritis and peptic ulcer disease. Clin Infect Dis . 1990; 12(Suppl 1):S87-93.
155. Graham DY, Lew GM, Evans DG et al. Effect of triple therapy (antibiotics plus bismuth) on duodenal ulcer healing: a randomized controlled trial. Ann Intern Med . 1991; 115:266-9. [PubMed 1854110]
156. Graham DY, Lew GM, Klein PD et al. Effect of treatment of Helicobacter pylori infection on the long-term recurrence of gastric or duodenal ulcer. A randomized, controlled study. Ann Intern Med . 1992; 116:705-8. [PubMed 1558340]
157. Cutler AF, Schubert TT. Patient factors affecting Helicobacter pylori eradication with triple therapy. Am J Gastroenterol . 1993; 88:505-9. [PubMed 8470629]
158. Logan RP, Gummett PA, Hegarty BT et al. Clarithromycin and omeprazole for Helicobacter pylori . Lancet . 1992; 25:340:239.
159. Hentschel E, Brandstatter G, Dragosics B et al. Effect of ranitidine and amoxicillin plus metronidazole on the eradication of Helicobacter pylori and the recurrence of duodenal ulcer. N Engl J Med . 1993; 328:308-12. [PubMed 8419816]
160. Graham DY. Treatment of peptic ulcers caused by Helicobacter pylori . N Engl J Med . 1993; 328:349-50. [PubMed 8419823]
161. Hosking SW, Ling TK, Yung MY et al. Randomised controlled trial of short term treatment to eradicate Helicobacter pylori in patients with duodenal ulcer. BMJ . 1992; 305:502-4. [PubMedCentral][PubMed 1392995]
162. Bell GD, Powell K, Burridge SM et al. Experience with 'triple' anti- Helicobacter pylori eradication therapy: side effects and the importance of testing the pre-treatment bacterial isolate for metronidazole resistance. Aliment Pharmacol Ther . 1992; 6:427-35. [PubMed 1420735]
163. Borody T, Andrews P, Mancuso N et al. Helicobacter pylori reinfection 4 years post-eradication. Lancet . 1992; 339:1295. [PubMed 1349686]
164. Hixson LJ, Kelley CL, Jones WN et al. Current trends in the pharmacotherapy for peptic ulcer disease. Arch Intern Med . 1992; 152:726-32. [PubMed 1558429]
165. Fennerty MB. Practice guidelines for treatment of peptic ulcer disease. JAMA . 1996; 276:1135. [PubMed 8827957]
166. Soll AH. Practice guidelines for treatment of peptic ulcer disease. JAMA . 1996; 276:1136-7.
167. Langtry HD, Wilde MI. Lansoprazole: an update of its pharmacological properties and clinical efficacy in the management of acid-related disorders. Drugs . 1997; 54:473-500. [PubMed 9279507]
168. TAP Pharmaceuticals, Inc. Prevacid® (lansoprazole) delayed-release capsules prescribing information. Deerfield, IL; 1997 Aug.
169. Garnett RG. Lansoprazole: a proton pump inhibitor. Ann Pharmacother . 1996; 30:1425. [PubMed 8968456]
170. Zimmerman AE, Katona BG. Lansoprazole: a comprehensive review. Pharmacotherapy . 1997; 17:308-26. [PubMed 9085323]
171. Hatlebakk JG, Nesje LB, Hausken T et al. Lansoprazole capsules and amoxicillin oral suspension in the treatment of peptic ulcer disease. Scand J Gastroenterol . 1995; 11:1053-7.