Carafate (Sucralfate) - Description and Clinical Pharmacology

DESCRIPTION

CARAFATE Tablets contain sucralfate and sucralfate is an α-D-glucopyranoside, β-D-fructofuranosyl-, octakis-(hydrogen sulfate), aluminum complex.

Tablets for oral administration contain 1 g of sucralfate.

Also contain: D & C Red #30 Lake, FD&C Blue #1 Lake, magnesium stearate, microcrystalline cellulose, and starch. Therapeutic category: antiulcer.

CLINICAL PHARMACOLOGY

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.

CLINICAL TRIALS

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 internation 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.

Maintenance Therapy After Healing of Duodenal Ulcer

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 1	30	38 2	42
Placebo	117	33	46	55	63

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 1	27
Placebo	46	54	65

In this study, prn antacids were permitted.

Data from placebo-controlled studies longer than 1 year are not available.