SUCRALFATE

SUCRALFATE

1 g Tablet

DRUG CATEGORY: Cytoprotector

BRAND NAME:Iselpin®

FORMULATION

Each tablet contains 1 g of Sucralfate

DESCRIPTION

Sucralfate is a white, amorphous powder which is soluble in strong acids and in alkalis but practically insoluble in water and in alcohol. It is a basic, aluminum complex of sucrose octasulfate.

Sucralfate has the chemical name, α-D-Glucopyranoside β-D-fructofuranosyl, octakis (hydrogen sulfate), aluminum complex. Its molecular formula is C₁₂H_mAl₁₆O_nS₈ (m and n are approximately 54 and 75 respectively, resulting in an average molecular of about 2086 daltons).

PHARMACOLOGY

Sucralfate is a unique anti-ulcer agent in that it is chemically unrelated to antacids, anticholinergics, or H₂receptor antagonists. Although the exact mechanism of action of Sucralfate has been fully defined, the therapeutic effects of the drug are the result of a local action rather than a systemic effect.

Sucralfate exerts a generalized cytoprotective effect, thereby preventing injury to the gastrointestinal mucosa. Sucralfate binds to the surface of both gastric and duodenal ulcers. Studies in human subjects and animal models demonstrate that Sucralfate forms an ulcer adherent complex with the proteinaceous exudate at the ulcer site. These insoluble complexes form a protective barrier over the ulcer lesion which affords sustained protection against the penetration and action of gastric acid, pepsin and bile. Studies both in human and animals show that Sucralfate protects the gastric mucosa from various irritants such as alcohol, acetylsalicylic acid and sodium taurocholate.

Sucralfate inhibits the proteolytic effect of pepsin and has been shown to adsorb bile salts in vitro. This substance exhibits only weak antacid activity.

Sucralfate does not alter gastric emptying time or normal digestive function.

PHARMACOKINETICS

Sucralfate is minimally absorbed from the gastrointestinal tract following oral administration. Animal studies indicate that only 3-5% of an oral dose reaches the systemic circulation. It appears in the blood as sucrose sulfate which is formed in the stomach following the reaction of Sucralfate with hydrochloric acid. Binding to the ulcer site for up to 6 hours following oral administration has been demonstrated. This prolonged action is due to the drug's viscous adhesiveness, slow reaction with gastric acid, and high affinity for damaged mucosa. In animal models, more that 90% of an orally administered dose of sucrose sulfate is excreted unchanged in feces in 48 hours. The small amount of Sucralfate that is absorbed as sucrose sulfate is excreted unchanged in urine within 48 hours.

INDICATIONS

Sucralfate is indicated in the treatment of duodenal ulcer, gastric ulcer, and chronic gastritis.

PRECAUTIONS

While short-term (usually up to 8 weeks) treatment can completely heal the ulcer, this disease state is a chronic and recurrent one. Sucralfate cannot be expected to alter the post-healing frequency or severity of ulceration.

Carcinogenesis, Mutagenesis and Impairment of Fertility – There was no evidence of carcinogenesis in mice and rats receiving oral Sucralfate in dosages up to 1 g/kg daily (12 times the usual human dosage) for 2 years. Mutagenicity studies have not been conducted. A reproduction study in rats given 38 times the usual human dosage of Sucralfate did not reveal evidence of impaired fertility. The effect of Sucralfate of human fertility is not known.

Using During Pregnancy – Teratogenicity studies in mice, rats and rabbits using dosages of Sucralfate up to 50 times the usual human dosage have revealed no evidence of harm to the fetus. There are, however, no adequate and well-controlled studies in pregnant women. Therefore, the safety of Sucralfate for use during pregnancy has not been established. It should not be used in pregnant women unless in the judgment of the physician, the expected benefits substantially outweigh the potential risk to the fetus.

Use During Lactation – it is not known if Sucralfate is excreted in breast milk. Because many drugs are excreted in breast milk, a decision should be made whether to discontinue nursing or to discontinue Sucralfate taking into account the importance of the drug to the mother and the potential risk to the infant.

Use in Children – the safety and effectiveness of Sucralfate in children have not been established; its use in this age group is therefore not recommended.

CONTRAINDICATIONS

1. Individuals with a known hypersensitivity to any of the ingredients.
2. Patients receiving dialysis (Long-term administration of this product may result in aluminum accumulation and toxicity. Aluminum toxicity has been implicated in encephalopathy and osteomalacia).

CAREFUL ADMINISTRATION

Patients with renal impairment (Long-term administration of this product may result in aluminum accumulation and toxicity. Aluminum toxicity has been implicated in encephalopathy and osteomalacia. Blood levels such as aluminum, phosphate, calcium, and alkaline phosphatase should be monitored periodically).

DRUG INTERACTIONS

1. Since this product may inhibit absorption of new quinolones such as ciprofloxacin hydrochloride and norfloxacin, this product should not be administered concomitantly with new quinolones.
2. Since this product may alter absorption and excretion of some co-administered drugs, this product should be carefully administered in concomitant therapy.

ADVERSE REACTIONS

Adverse reactions to Sucralfate in clinical trials were minor and rarely led to discontinuation of the drug. In studies including over 2500 patients treated with Sucralfate, adverse effects were only reported in 121 (4.7%). The most frequent complaint was constipation (2.2%). Other adverse effects, reported in not greater that 1 in every 350 patients treated were diarrhea, nausea, gastric discomfort, indigestion, dry mouth, rash, pruritus, back pain dizziness, drowsiness, and vertigo.

ADMINISTRATION TO THE ELDERLY

Since physiologic function are usually reduced in elderly patients, caution must be exercised with careful consideration give to dosage.

DOSAGE AND ADMINISTRATION

The recommended adult oral dosage is 1 g four times a day 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.

Although healing with Sucralfate may occur during the first week or two, continuation of treatment is suggested for 4-8 weeks unless healing has been demonstrated by X-ray or endoscopic examination. In resistant cases, up to 12 weeks may be needed.

OVERDOSAGE

There is limited information available on eh acute toxicity of Sucralfate. Following oral administration of a single 12 g dose to healthy adults, no serious toxicity was observed. Acute oral toxicity studies in animals with doses to 12 g/kg could not establish a lethal dose. Risks associated with overdosage should, therefore, be minimal.

STORAGE CONDITIONS

Store at a temperature not exceeding 25^oC. Keep bottle tightly closed.