Prescription Drug Information: Sucralfate

SUCRALFATE- sucralfate tablet
Teva Pharmaceuticals USA, Inc.

DESCRIPTION

Sucralfate, USP is an α-D-glucopyranoside, β-D-fructofuranosyl-, octakis(hydrogen sulfate), aluminum complex.

R = SO₃ Al(OH)₂

Tablets for oral administration contain 1 g of sucralfate, USP and the following inactive ingredients: corn starch, magnesium stearate, and microcrystalline cellulose.

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 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.

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 (%)

* p < 0.05 † p < 0.01
Months of Therapy
Drug	n	1	2	3	4
Sucralfate	122	20*	30*	38†	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 (%)

* p < 0.002
Drug	n	6 months	12 months
Sucralfate	48	19*	27*
Placebo	46	54	65

In this study, prn antacids were permitted.

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

INDICATIONS AND USAGE

Sucralfate tablets, USP are indicated in:

• Short-term treatment (up to 8 weeks) of active duodenal ulcer. While healing with sucralfate may occur during the first week or two, treatment should be continued for 4 to 8 weeks unless healing has been demonstrated by x-ray or endoscopic examination.
• Maintenance therapy for duodenal ulcer patients at reduced dosage after healing of acute ulcers.

CONTRAINDICATIONS

Sucralfate tablets are contraindicated in patients with known hypersensitivity reactions to the active substance or to any of the excipients.

PRECAUTIONS

The physician should read the PRECAUTIONS section when considering the use of this drug in pregnant or pediatric patients, or patients of childbearing potential.

Duodenal ulcer is a chronic, recurrent disease. While short-term treatment with sucralfate can result in complete healing of the ulcer, a successful course of treatment with sucralfate should not be expected to alter the post healing frequency or severity of duodenal ulceration.

Isolated reports of sucralfate tablet aspiration with accompanying respiratory complications have been received. Therefore, sucralfate tablets should be used with caution by patients who have known conditions that may impair swallowing, such as recent or prolonged intubation, tracheostomy, prior history of aspiration, dysphagia, or any other conditions that may alter gag and cough reflexes, or diminish oropharyngeal coordination or motility.

Special Populations

Chronic Renal Failure and Dialysis Patients

When sucralfate is administered orally, small amounts of aluminum are absorbed from the gastrointestinal tract. Concomitant use of sucralfate with other products that contain aluminum, such as aluminum-containing antacids, may increase the total body burden of aluminum. Patients with normal renal function receiving the recommended doses of sucralfate and aluminum-containing products adequately excrete aluminum in the urine. Patients with chronic renal failure or those receiving dialysis have impaired excretion of absorbed aluminum. In addition, aluminum does not cross dialysis membranes because it is bound to albumin and transferrin plasma proteins. Aluminum accumulation and toxicity (aluminum osteodystrophy, osteomalacia, encephalopathy) have been described in patients with renal impairment. Sucralfate should be used with caution in patients with chronic renal failure.

Drug Interactions

Some studies have shown that simultaneous sucralfate administration in healthy volunteers reduced the extent of absorption (bioavailability) of single doses of the following: cimetidine, digoxin, fluoroquinolone antibiotics, ketoconazole, l-thyroxine, phenytoin, quinidine, ranitidine, tetracycline, and theophylline. Subtherapeutic prothrombin times with concomitant warfarin and sucralfate therapy have been reported in spontaneous and published case reports. However, two clinical studies have demonstrated no change in either serum warfarin concentration or prothrombin time with the addition of sucralfate to chronic warfarin therapy.

The mechanism of these interactions appears to be nonsystemic in nature, presumably resulting from sucralfate binding to the concomitant agent in the gastrointestinal tract. In all case studies to date (cimetidine, ciprofloxacin, digoxin, norfloxacin, ofloxacin, and ranitidine), dosing the concomitant medication 2 hours before sucralfate eliminated the interaction. Because of the potential of sucralfate to alter the absorption of some drugs, sucralfate should be administered separately from other drugs when alterations in bioavailability are felt to be critical. In these cases, patients should be monitored appropriately.