Can sucralfate (Andapsin) be used for protection against ulcers or dyspepsia induced by nonsteroida

Fråga: Can sucralfate (Andapsin) be used for protection against ulcers or dyspepsia induced by nonsteroidal anti-inflammatory drugs?

Sammanfattning: Sucralfate appears to protect against gastric mucosal damage associated with single and multiple doses of acetylsalicylic acid. Although clinical benefit has been reported for the use of sucralfate in patients with peptic disease associated with non- steroidal antiinflammatory drugs, further studies are required to define its role in the management of this group of patients.

Svar: Sucralfate is an aluminum salt of sucrose octasulfate. At pH below 4, sucralfate forms a thick viscous gel that binds selectively to ulcers of the stomach and the duodenum, forming an acid-resistant layer that promotes healing. It adsorbs pepsin, trypsin, and bile acids (1). Sucralfate may also stimulate the release of prostaglandins (2).

Data from a number of clinical trials indicate that sucralfate is effective in the treatment of both duodenal and gastric ulcer, but the rate of healing of gastric ulcer is less than for duodenal ulcer (1).

Results of three studies with healthy volunteers (3-5) suggest that sucralfate (1 gram, four times daily) may have a protective effect against gastric mucosal damage induced by single and multiple doses of acetylsalicylic acid (ASA). Eight of 12 healthy volunteers on sucralfate experienced complete protection against gastric mucosal damage from ingestion of ASA 3600 mg daily for four days (3). Sucralfate was shown to significantly reduce endoscopic changes in the gastric mucosa resulting from a 1200 mg dose of ASA (4). ASA-induced gastric bleeding was significantly reduced by sucralfate as compared to placebo in a double-blind study (5). However, in a placebo controlled, double-blind, crossover study the difference in fecal blood loss was not statistically significant (6).

A reduction of the bioavailability of non-steroidal anti-inflammatory drugs (NSAIDs) does not appear to be involved in the protective action of sucralfate. Salicylate levels were not affected by the administration of sucralfate (3). Although absorption of naproxen is delayed by sucralfate, overall bioavailability is not affected (7). It has been suggested that the protective action of sucralfate on the gastric mucosa of humans may be related to stimulation of endogenous prostaglandins, as the protective effect is inhibited by indomethacin (4). However, sucralfate does not influence ASA-induced decrease of prostaglandins and thromboxane B2 (5).

The use of sucralfate, one gram four times daily, for the treatment of gastrointestinal symptoms and gastric mucosal damage associated with nonsteroidal anti-inflammatory drugs was assessed in a placebo-controlled, double-blind, randomized trial (8). After four weeks of sucralfate therapy, there was significant reduction of both peptic symptom frequency and intensity as compared with patients receiving placebo. There was also significant reduction in endoscopically assessed mucosal lesion scores as compared with baseline in sucralfate treated patients, whereas no improvement was observed with those receiving placebo.

In an open-label trial, sucralfate (1 gram four times daily) was compared to ranitidine (150 mg twice daily) in 67 patients with rheumatic disease and endoscopically diagnosed gastric or duodenal ulcers (9). The effects of these two drugs were assessed in patients who continued taking various non-steroidal anti-inflammatory drugs versus those who discontinued them. Although there was a 14 per cent lower overall healing rate between those who continued taking NSAIDs compared to those who discontinued NSAIDs, the difference was not statistically significant (probably due to small numbers of patients). Average healing times were identical for 25 patients on sucralfate and 27 patients given ranitidine. 1 Goodman and Gilman, The pharmacological basis of therapeutics. 1985; 7th ed: 988 2 Avery´s, Drug treatment. 1987; 3rd ed: 748 3 Tesler MA, Lim ES: Protection of gastric mucosa by sucralfate from aspirin-induced erosions. J Clin Gastroenterol 1981; 3(suppl 2): 175-179 4 Stern AI, Ward F, Hartley G: Protective effect of sucralfate against aspirin-induced damage to the human gastric mucosa. Am J Med 1987; 83(suppl 3B): 83-85 5 Konturek SJ, Kwiecien N, Obtulowicz W, Oleksy J: Gastroprotection by sucralfate against acetylsalicylic acid in humans. Role of endogenous prostaglandins. Scand J Gastroenterol 1987; 22(suppl 140): 19-22 6 Malchow-Moller A, Ranlov PJ: Does sucralfate reduce acetylsalicylic acid-induced gastric mucosal bleeding? Scand J Gastroenterol 1987; 22: 550-552 7 Caille G, du Souich P, Gervais P, Besner JG, Vezina M: Effects of concurrent sucralfate administration on pharmacokinetics of naproxen. Am J Med 1987; 83(suppl 3B): 67-73 8 Caldwell JR, Roth SH, Wu WC, Semble EL, Castell DO, Heller MD, Marsh Wh: Sucralfate treatment of nonsteroidal anti-inflammatory drug-induced gastrointestinal symptoms and mucosal damage. Am J Med 1987; 83(suppl 3B): 74-82 9 Malchow-Moller A: Treatment of peptic ulcer induced by nonsteroidal anti-inflammatory drugs. Scand J Gastroenterol 1987; 22(suppl 127): 87-91