Sucralfate

Sucralfate: A Comprehensive Review

Sucralfate is a unique gastroprotective agent, primarily indicated for the treatment of peptic ulcer disease and related gastrointestinal conditions. Unlike most pharmacologic interventions that exert systemic effects, sucralfate acts locally within the gastrointestinal tract. Composed of sucrose octasulfate and aluminium hydroxide, it reacts with gastric acid to form a sticky, gel-like complex that adheres to ulcerated mucosa. This barrier protects damaged tissue from the corrosive effects of acid, pepsin, and bile salts, thereby facilitating mucosal healing without significantly altering gastric pH.

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Therapeutic Indications

Sucralfate is principally used in the treatment and prevention of duodenal ulcers. It also has off-label applications in gastric ulcers, gastroesophageal reflux disease (GERD), stress-related mucosal injury, and oral mucositis in oncology patients. Additionally, it is beneficial in managing rectal inflammation caused by radiation therapy (radiation proctitis) and in preventing gastrointestinal bleeding among critically ill patients.

Dosage and Administration

The standard adult dosage is 1 g four times daily, ideally taken on an empty stomach before meals and at bedtime. Maintenance therapy typically involves 1 g twice daily. Sucralfate tablets may be taken whole or crushed and suspended in water for patients with dysphagia. For paediatric patients or those with difficulty swallowing, the liquid suspension (1 g/10 mL) is recommended. Administering the medication at the appropriate time is essential for optimal mucosal adherence and efficacy.

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Dose Adjustments in Special Populations

• Renal Impairment: In patients with chronic kidney disease, the aluminium component of sucralfate may accumulate, leading to toxicity such as encephalopathy and osteomalacia. Close monitoring of renal function and serum aluminium levels is advised during prolonged therapy.

• Hepatic Impairment: Given its negligible systemic absorption, sucralfate usually does not require dosage adjustments in hepatic dysfunction. However, clinicians should assess individual risk factors before prescribing.

• Pregnancy: Categorised as pregnancy category B, sucralfate is considered safe based on animal studies and clinical experience. Its minimal systemic absorption and localised action make it suitable for managing GERD and other gastric symptoms during pregnancy under medical supervision.

Adverse Effects

Sucralfate is generally well tolerated. The most common side effect is constipation, occurring in approximately 2% of users. Other reported adverse events include bloating, nausea, dry mouth, and epigastric discomfort. Rarely, hypersensitivity reactions such as urticaria or angioedema have been observed. In renally impaired patients, chronic use can result in aluminium toxicity, underscoring the need for vigilant monitoring.

Mechanism of Action

In an acidic environment, sucralfate undergoes polymerisation, forming a viscous gel that selectively binds to ulcerated mucosa. This protective barrier persists for up to six hours, shielding the lesion from irritants such as gastric acid and enzymes. Additionally, sucralfate enhances mucosal defence by stimulating prostaglandin production, increasing bicarbonate secretion, and promoting epithelial regeneration.

Combination Therapy and Enteral Administration Considerations

Sucralfate is often prescribed alongside proton pump inhibitors (PPIs) like omeprazole or H2 receptor antagonists such as famotidine. Because it may reduce the bioavailability of concurrently administered oral medications, a two-hour interval between doses is recommended. When used via enteral feeding tubes, flushing the tube before and after administration helps prevent clogging.

Available Formulations

Formulation	Strength	Recommended Use
Tablet	1 g	Oral; may be crushed or suspended
Oral Suspension	1 g/10 mL	Preferred for paediatrics and dysphagia
Sachet	1 g	Mix in water for oral administration

Pharmacokinetics and Pharmacodynamics

Systemic absorption of sucralfate is minimal (<5%). Its onset of action is within 1–2 hours, with protective effects lasting up to 8 hours. Although it lacks direct antimicrobial properties, it enhances mucosal defences and can reduce colonisation by pathogens such as Helicobacter pylori. Its pharmacodynamic activity includes stimulation of local prostaglandin synthesis and mucosal repair mechanisms.

Drug Interactions

Sucralfate may form insoluble complexes with various orally administered drugs, including digoxin, warfarin, phenytoin, fluoroquinolones, levothyroxine, and tetracyclines, thereby reducing their bioavailability. To mitigate this, stagger administration by at least two hours. Additional caution is needed with citrate-containing compounds, which may increase aluminium absorption and toxicity.

Comparative Table of Gastroprotective Agents

Drug	Mechanism	Dosing Regimen	Key Considerations
Sucralfate	Mucosal barrier formation	4 times/day	Minimal systemic absorption
Omeprazole	Proton pump inhibition	Once daily	Highly effective acid suppression
Ranitidine	H2 receptor antagonism	Twice daily	Withdrawn due to NDMA contamination risks
Misoprostol	Prostaglandin analogue	4 times/day	Teratogenic; common GI side effects

Clinical Precautions

Use sucralfate with caution in patients with renal impairment, especially those on dialysis, due to the risk of aluminium toxicity. Ensure adequate fluid intake to reduce constipation. For maximum therapeutic benefit, administer the drug on an empty stomach. Older adults may require additional monitoring for gastrointestinal side effects.

Overdose and Toxicity

Overdose is rare and generally benign. Symptoms may include nausea, vomiting, and abdominal discomfort. The main concern in overdose, particularly in patients with renal insufficiency, is aluminium accumulation. Supportive measures such as fluid therapy and gastrointestinal decontamination are typically sufficient. In severe toxicity, chelation with deferoxamine may be required.

Guideline Updates (2025)

The British Society of Gastroenterology's 2025 guidelines reaffirm sucralfate’s value in managing stress-related mucosal disease, especially in mechanically ventilated ICU patients. Sucralfate is also recognised as a safe and effective option for treating pregnancy-associated GERD when PPIs are contraindicated. These updates support a broader use of non-systemic mucosal protectants.

Key Clinical Insight

Sucralfate’s mechanism, focused on mucosal protection rather than acid suppression, distinguishes it from other ulcer treatments. This makes it particularly suitable for patients who cannot tolerate acid-suppressive therapies.

Did You Know?

Sucralfate’s stability and minimal systemic effects led to its consideration for space medicine applications. It is also being investigated for use in veterinary medicine, particularly for managing gastrointestinal ulcers in small animals.

References

1. British National Formulary (BNF), 2025 Edition

2. NICE Guidelines on Peptic Ulcer and GERD, 2025 Update

3. Goodman & Gilman’s The Pharmacological Basis of Therapeutics, 14th Ed.

4. Martindale: The Complete Drug Reference, 40th Edition

5. British Society of Gastroenterology Guidelines, 2025

6. Journal of Clinical Gastroenterology, Feb 2025

7. International GERD Management Consensus, 2025 Update