Sucralfate - Drug Monograph

Introduction

Sucralfate is a complex of sulfated sucrose and aluminum hydroxide that functions as a locally-acting gastrointestinal medication. First approved by the FDA in 1981, it remains an important therapeutic option for various acid-peptic disorders. Unlike systemic acid-suppressing agents, sucralfate exerts its effects primarily through local mechanisms within the gastrointestinal tract, making it a unique addition to the gastroenterological armamentarium.

Mechanism of Action

Sucralfate's mechanism of action is multifaceted and primarily local. In the acidic environment of the stomach, sucralfate dissociates into its negatively charged sucrose sulfate ions and aluminum hydroxide. These sucrose sulfate polymers polymerize and form a viscous, adhesive substance that binds selectively to eroded or ulcerated gastrointestinal mucosa, creating a protective barrier that lasts approximately 6 hours. This barrier:

• Protects ulcers from further damage by acid, pepsin, and bile
• Adsorbs pepsin and bile acids
• Stimulates mucosal prostaglandin synthesis and bicarbonate secretion
• Enhances mucosal defense mechanisms through growth factor binding

The drug requires an acidic environment (pH <4) for optimal activation and efficacy.

Indications

FDA-approved indications:

• Short-term treatment (up to 8 weeks) of active duodenal ulcers
• Maintenance therapy for healed duodenal ulcers

Off-label uses (supported by clinical evidence):

• Prevention of stress ulcers in critically ill patients
• Treatment of gastric ulcers
• Management of gastroesophageal reflux disease (GERD)
• Treatment of oral and esophageal ulcers
• Prevention of NSAID-induced gastrointestinal damage

Dosage and Administration

• Active duodenal ulcers: 1g orally four times daily on an empty stomach (1 hour before meals and at bedtime)
• Maintenance therapy: 1g orally twice daily on an empty stomach

• Should be taken on an empty stomach (at least 1 hour before meals)
• Tablets should be swallowed whole with water
• Antacids may be used concomitantly but should be administered at least 30 minutes before or after sucralfate
• Typical treatment duration: 4-8 weeks for active ulcers

• Renal impairment: Use with caution; aluminum may accumulate
• Hepatic impairment: No dosage adjustment typically needed
• Elderly: No specific dosage adjustment, but monitor for constipation
• Pediatrics: Safety and effectiveness not established for children

Pharmacokinetics

Contraindications

• Hypersensitivity to sucralfate or any component of the formulation
• Patients with known aluminum toxicity
• Patients with dialysis-dependent renal failure (relative contraindication)

Warnings and Precautions

Drug Interactions

• Antacids: May decrease sucralfate efficacy (separate administration by at least 30 minutes)
• Warfarin: May decrease INR (monitor closely and adjust warfarin dose as needed)
• Digoxin: May decrease serum digoxin levels (monitor levels)
• Phenytoin: May decrease phenytoin absorption (separate administration by at2 hours)
• Quinolone antibiotics: Markedly reduces absorption (separate administration by at least 2 hours before or 6 hours after sucralfate)
• Levothyroxine: Decreases absorption (separate administration by at least 4 hours)
• Ketoconazole: Decreases absorption (separate administration by at least 2 hours)

Adverse Effects

• Constipation (2%)
• Dry mouth
• nausea
• Gastric discomfort
• Diarrhea
• Indigestion

• Back pain
• Dizziness
• Drowsiness
• Skin rash
• Pruritus

• Aluminum toxicity (in renal impairment)
• Intestinal obstruction
• Bezoar formation
• Hypophosphatemia
• Allergic reactions including anaphylaxis

Monitoring Parameters

• Symptom improvement (pain relief, healing)
• Signs of gastrointestinal bleeding if indicated

• Bowel function (constipation)
• Renal function (serum creatinine, BUN)
• Serum aluminum levels in patients with renal impairment or long-term use
• Serum phosphate levels with prolonged therapy
• Signs of aluminum toxicity (microcytic anemia, osteomalacia, encephalopathy)

• Endoscopic confirmation of ulcer healing if clinically indicated
• Assessment of need for continued maintenance therapy

Patient Education

• Take on an empty stomach (1 hour before meals and at bedtime)
• Swallow tablets whole with a full glass of water
• Do not crush or chew tablets
• Space other medications at least 2 hours apart from sucralfate doses
• Report severe constipation or abdominal discomfort
• Notify all healthcare providers about sucralfate use
• Diabetic patients should be aware of sucrose content
• Complete full course of therapy even if symptoms improve
• Follow recommended dietary modifications for ulcer management

• Store at room temperature (15-30°C)
• Keep in original container with lid tightly closed
• Protect from moisture

References

1. US Food and Drug Administration. (2021). Sucralfate prescribing information. 2. McCarthy DM. (1991). Sucralfate. New England Journal of Medicine, 325(14), 1017-1025. 3. Lanza FL. (1989). Review of sucralfate in the treatment of peptic ulcer disease. Journal of Clinical Gastroenterology, 11(1), 1-6. 4. Nagashima R. (1981). Mechanisms of action of sucralfate. Journal of Clinical Gastroenterology, 3(2), 117-127. 5. Lam S. (1995). Sucralfate in the prevention of NSAID-induced gastropathy. Journal of Rheumatology, 22(10), 2013-2016. 6. American Society of Health-System Pharmacists. (2023). AHFS Drug Information: Sucralfate. 7. Micromedex Solutions. (2023). Sucralfate Drug Monograph. 8. Thomson MICROMEDEX. (2023). Sucralfate: Drug Interactions. 9. National Institutes of Health. (2022). LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. 10. UpToDate. (2023). Sucralfate: Drug information.