Source: FDA, National Drug Code (US) Revision Year: 2020
Sucralfate is only minimally absorbed from the gastrointestinal tract. The small amounts of the sulfated disaccharide that are absorbed are excreted primarily in the urine.
Although the mechanism of sucralfate’s ability to accelerate healing of duodenal ulcers remains to be fully defined, it is known that it exerts its effect through a local, rather than systemic, action. The following observations also appear pertinent:
1. Studies in human subjects and with animal models of ulcer disease have shown that sucralfate forms an ulcer-adherent complex with proteinaceous exudate at the ulcer site.
2. In vitro, a sucralfate-albumin film provides a barrier to diffusion of hydrogen ions.
3. In human subjects, sucralfate given in doses recommended for ulcer therapy inhibits pepsin activity in gastric juice by 32%.
4. In vitro, sucralfate adsorbs bile salts.
These observations suggest that sucralfate’s antiulcer activity is the result of formation of an ulcer-adherent complex that covers the ulcer site and protects it against further attack by acid, pepsin, and bile salts. There are approximately 14 to 16 mEq of acid-neutralizing capacity per 1 g dose of sucralfate.
Chronic oral toxicity studies of 24 months' duration were conducted in mice and rats at doses up to 1 g/kg (12 times the human dose).
There was no evidence of drug-related tumorigenicity. A reproduction study in rats at doses up to 38 times the human dose did not reveal any indication of fertility impairment. Mutagenicity studies were not conducted.
h3.Acute Duodenal Ulcer
Over 600 patients have participated in well-controlled clinical trials worldwide. Multicenter trials conducted in the United States, both of them placebo-controlled studies with endoscopic evaluation at 2 and 4 weeks, showed:
STUDY 1:
| Treatment Groups | Ulcer Healing/No. Patients | |
|---|---|---|
| 2 wk | 4 wk (Overall) | |
| Sucralfate | 37/105 (35.2%) | 82/109 (75.2%) |
| Placebo | 26/106 (24.5%) | 68/107 (63.6%) |
STUDY 2:
| Treatment Groups | Ulcer Healing/No. Patients | |
|---|---|---|
| 2 wk | 4 wk (Overall) | |
| Sucralfate | 8/24 (33%) | 22/24 (92%) |
| Placebo | 4/31 (13%) | 18/31 (58%) |
The sucralfate-placebo differences were statistically significant in both studies at 4 weeks but not at 2 weeks. The poorer result in the first study may have occurred because sucralfate was given 2 hours after meals and at bedtime rather than 1 hour before meals and at bedtime, the regimen used in international studies and in the second United States study. In addition, in the first study liquid antacid was utilized as needed, whereas in the second study antacid tablets were used.
Two double-blind randomized placebo-controlled U.S. multicenter trials have demonstrated that sucralfate (1 g bid) is effective as maintenance therapy following healing of duodenal ulcers.
In one study, endoscopies were performed monthly for 4 months. Of the 254 patients who enrolled, 239 were analyzed in the intention-to-treat life table analysis presented below.
| Duodenal Ulcer Recurrence Rate (%) | |||||
|---|---|---|---|---|---|
| Drug | Months of Therapy | ||||
| n | 1 | 2 | 3 | 4 | |
| CARAFATE | 122 | 20* | 30* | 38† | 42† |
| Placebo | 117 | 33 | 46 | 55 | 63 |
* P<0.05,
† P<0.01
In this study, prn antacids were not permitted.
In the other study, scheduled endoscopies were performed at 6 and 12 months, but for-cause endoscopies were permitted as symptoms dictated. Median symptom scores between the sucralfate and placebo groups were not significantly different. A life table intention-to-treat analysis for the 94 patients enrolled in the trial had the following results:
| Duodenal Ulcer Recurrence Rate (%) | |||
|---|---|---|---|
| Drug | n | 6 months | 12 months |
| CARAFATE | 48 | 19* | 27* |
| Placebo | 46 | 54 | 65 |
* P<0.002
In this study, prn antacids were permitted.
Data from placebo-controlled studies longer than 1 year are not available.
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