Sucralfate


Continuing Education Activity

Sucralfate is a medication used to treat duodenal ulcers, epithelial wounds, chemotherapy-induced mucositis, radiation proctitis, ulcers in Behcet disease, and burn wounds. Sucralfate exhibits its action by forming a protective layer, increasing bicarbonate production, exhibiting anti-peptic effects, promoting tissue growth, regeneration, and repair. The most common side effect seen with this drug is constipation. Some of the more severe side effects are hypophosphatemia, aluminum intoxication seen in end-stage disease patients. The medication has a relatively safe profile as there is negligible absorption from the enteral system. This activity outlines the indications, mechanism of action, methods of administration, significant adverse effects, contraindications, toxicity, and monitoring, of sucralfate, so providers can direct patient therapy in conditions where it has therapeutic benefit as part of the interprofessional team.

Objectives:

  • Identify the mechanism of action of sucralfate.
  • Describe the adverse effects of sucralfate.
  • Review the toxicity of sucralfate.
  • Summarize interprofessional team strategies for improving care coordination and communication to advance sucralfate use and improve outcomes.

Indications

Sucralfate is a unique anti-ulcer drug. It is a basic aluminum salt of sucrose octasulfate. The labeled use of sucralfate is as below:

Treatment of duodenal ulcer: Sucralfate is FDA approved for the treatment of duodenal ulcers up to 8 weeks (short term). Duodenal ulcers are treated with 1g four times daily for eight weeks, followed by 1 g twice daily for maintenance therapy. The efficacy of sucralfate in the treatment of duodenal ulcers is shown to be comparable to that of cimetidine and intensive antacid therapy.[1] Sucralfate forms a protective coat and protects the gastric mucosa from pepsin, pectic acid, and bile salts. It binds to positively charged proteins in exudates, forming a thick viscous substance locally. 

Sucralfate has also been used to treat various other conditions that are non-FDA approved, as outlined below.

  1. Dyspepsia: It is shown to reduce the frequency and intensity of dyspeptic symptoms during NSAID therapy, and the efficacy is similar to that of an H-2 receptor blocker.[2] 
  2. Treatment of epithelial wounds: Sucralfate has also seen use as a topical drug in treating various epithelial wounds such as ulcers, inflammatory dermatitis, mucositis, and burns wounds. Several studies have been conducted to study the efficacy of sucralfate in the treatment of epithelial wounds. A study done by Tsakayannis et al. showed that the venous ulcer that failed conventional therapy responded to treatment with topical sucralfate.[3] Sucralfate increases the bio-availability of growth factors, especially fibroblast growth factor (FGF), which has a pivotal role in angiogenesis and, in turn, promotes epithelial wound healing.  
  3. Treatment of chemotherapy-induced mucositis: A study done by McCullough showed that high potency sucralfate accelerates the activation of growth factor and is useful in treating chemotherapy-induced mucositis of the oropharynx and alimentary tract. This resulted from administering 1.5 g of sucralfate three times daily at the onset of mucositis for two days, followed by 1.5 g two times daily throughout the course of cancer therapy and two weeks after the completion of treatment. 
  4. Treatment of radiation proctitis: Sucralfate paste enema has shown clinical improvement in hemorrhagic radiation proctitis treatment. This therapy uses a low volume paste in an enema applicator, and pre and post-treatment improvements were assessed using clinical proctitis scores with a positive outcome.[4] A study done by Kocchar et al. has shown that sucralfate enema is better than oral sulfasalazine in the short-term treatment of radiation proctitis.[5]
  5. Prevention of ulceration of diversion colitis: The use of enemas containing sucralfate is shown to preserve the mucus layer covering the epithelium, thereby reducing inflammation in diversion colitis. The concentration of sucralfate used in the enema is 2 g/kg/day.[6] 
  6. Stress ulcer prophylaxis in ventilated patients: Research has shown that sucralfate is better for stress ulcer prophylaxis when compared to H-2 blockers or antacids in patients receiving ventilation therapy as the latter increases the pH of gastric contents causing stagnation of gram-negative bacilli and subsequently increasing the risk of nosocomial pneumonia.[7]
  7. Behcet Disease: Topical sucralfate 1 g/5mL four times daily alone or in combination with topical corticosteroids reduced pain and promotes healing of oral ulcers in Behcet disease. Sucralfate in the form of suspension is the dosage form for the treatment of oral ulcers in Behcet disease.

Mechanism of Action

The principal action of sucralfate is unknown. The following actions of sucralfate have been the object of study in vitro, but the in vivo actions remain unknown[2]

  1. Antipeptic effects - It prevents hydrolysis by preventing the formation of the enzyme-substrate complex. It adsorbs to pepsin and decreases its concentration.
  2. Site-protective effects - By forming a polyanion gel, it acts as a physical barrier between luminal contents and mucosa.
  3. Effects on mucus - Increases mucous hydrophobicity, viscosity, sulfation, and aluminum and carbohydrate content, which leads to improved mucosal protection from acid. It also increases the production of mucus by increasing prostaglandin production. Sucralfate prevents the breakdown of mucus by pepsin A, reducing ulcerogenesis.
  4. Effect on bicarbonate output - It increases prostaglandin-dependent and independent production of bicarbonate by stomach and duodenum. 
  5. Effects on tissue growth, regeneration, and repair - It binds epidermal growth factor and tissue growth factor to tissues and facilitates repair. 

Administration

Sucralfate administration can be via oral, rectal, and topical routes:

  1. Oral forms:
    • Tablet - Sucralfate is a basic aluminum salt of sucrose octasulfate. When given orally, it disintegrates in the stomach in the presence of acid and binds to normal and damaged mucosa forming a protective layer. It releases aluminum and binds to positively charged compounds like proteins, peptides, glycoproteins, and glycolipoproteins, forming an adhesive layer, thereby protecting the mucosa. The onset of action is within 1 to 2 hours, and 1 g of sucralfate can neutralize 14 to 16 mEq of acid. The tablets are available as 1 g tablets.
    • Suspension: Suspension is available as 1 g/10 mL or 500 mg/5mL. 
  2. Rectal: Sucralfate tablets have been mixed with water to form a sucralfate paste enema: 2 tablets (that is 2g of sucralfate) mixed with 4.5 ml of water and is an option in the treatment of hemorrhagic radiation proctitis. Sucralfate enema is also useful in solitary rectal ulcer syndrome and diversion colitis.
  3. Topical: Sucralfate is used topically in the treatment of skin conditions and also for mucosal ulcers. 

Adverse Effects

Sucralfate acts locally with negligible absorption making it relatively safe. The most common side effect is constipation seen in 1-10% of patients. Hyperglycemia is also reported in diabetic patients using sucralfate. Some of the other negligible side effects are nausea, vomiting, flatulence, headache, dry mouth, pruritis, skin rash, gastric bezoar formation, aluminum intoxication, hypophosphatemia. Inadvertent IV use of sucralfate has caused fatal complications such as pulmonary emboli and cerebral edema.

Long-term users of sucralfate are shown to retain aluminum that is negligible, except when a patient has renal insufficiency. Uremia causes increased absorption of aluminum from the gut, and the quantity of aluminum absorbed is similar to that of aluminum hydroxide. Sucralfate should be used with caution in patients with end-stage renal disease or avoided altogether to prevent aluminum intoxication.[2][8]

Sucralfate has several drug interactions and can decrease the serum concentrations of digoxin, levothyroxine, furosemide, quinolones, oral phosphate supplements, warfarin, antiretrovirals like raltegravir, bisphosphonates, among others. Sucralfate administration should have at least a 2-hour gap from the administration of these medications. Multivitamins can increase the serum concentration of sucralfate and aluminum. A few medications like antacids administered within 15 minutes of sucralfate can reduce its efficacy by decreasing the binding ability of sucralfate to gastric ulcers.

Contraindications

Documented hypersensitivity to sucralfate is an absolute contraindication as it can cause an anaphylactic reaction. Some of the relative contraindications include end-stage renal disease, uncontrolled diabetes mellitus with hyperglycemia, impaired swallowing/gag reflex. Sucralfate was an FDA category B medication under the prior pregnancy classification system, and its safety in pregnancy, during breastfeeding, and in infants is not established.

Monitoring

No therapeutic monitoring has been recommended for this medication as it undergoes minimal absorption from the enteral system.

Toxicity

Risks associated with sucralfate overdosing are minimal as sucralfate has minimal absorption from the gastrointestinal system; many patients that overdosed on sucralfate remained asymptomatic. Due to the small amount of aluminum absorbed with oral intake of sucralfate, it can cause aluminum accumulation and toxicity in patients with chronic kidney disease or those receiving dialysis.

Enhancing Healthcare Team Outcomes

Patient satisfaction and relief of symptoms are very valuable to caregivers in the age of medicine. Managing the side effects of chemotherapy and radiation has become a challenge and encountered more often by physicians with new treatment regimens and prolonged survival of oncology patients. The incidence of peptic ulcer disease is also on the rise, with population migration from regions endemic to Helicobacter pylori, lifestyle changes, and overuse of pain medications like NSAIDs. Understanding and using medications like sucralfate requires the effort of an interprofessional healthcare team, including clinicians, mid-level practitioners, nurses, and pharmacists can provide the best patient outcomes. [Level 5]


Article Details

Article Author

Pujitha Kudaravalli

Article Editor:

Savio John

Updated:

3/31/2021 10:03:34 AM

PubMed Link:

Sucralfate

References

[1]

Garnett WR, Sucralfate--alternative therapy for peptic-ulcer disease. Clinical pharmacy. 1982 Jul-Aug;     [PubMed PMID: 6764389]

[2]

McCarthy DM, Sucralfate. The New England journal of medicine. 1991 Oct 3;     [PubMed PMID: 1886624]

[3]

Masuelli L,Tumino G,Turriziani M,Modesti A,Bei R, Topical use of sucralfate in epithelial wound healing: clinical evidences and molecular mechanisms of action. Recent patents on inflammation     [PubMed PMID: 19832693]

[4]

McElvanna K,Wilson A,Irwin T, Sucralfate paste enema: a new method of topical treatment for haemorrhagic radiation proctitis. Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland. 2014 Apr;     [PubMed PMID: 24299100]

[5]

Kochhar R,Patel F,Dhar A,Sharma SC,Ayyagari S,Aggarwal R,Goenka MK,Gupta BD,Mehta SK, Radiation-induced proctosigmoiditis. Prospective, randomized, double-blind controlled trial of oral sulfasalazine plus rectal steroids versus rectal sucralfate. Digestive diseases and sciences. 1991 Jan;     [PubMed PMID: 1670631]

[6]

Fernandez OOA,Pereira JA,Campos FG,Araya CM,Marinho GE,Novo RS,Oliveira TS,Franceschi YT,Martinez CAR, EVALUATION OF ENEMAS CONTAINING SUCRALFATE IN TISSUE CONTENT OF MUC-2 PROTEIN IN EXPERIMENTAL MODEL OF DIVERSION COLITIS. Arquivos brasileiros de cirurgia digestiva : ABCD = Brazilian archives of digestive surgery. 2017 Apr-Jun;     [PubMed PMID: 29257850]

[7]

Driks MR,Craven DE,Celli BR,Manning M,Burke RA,Garvin GM,Kunches LM,Farber HW,Wedel SA,McCabe WR, Nosocomial pneumonia in intubated patients given sucralfate as compared with antacids or histamine type 2 blockers. The role of gastric colonization. The New England journal of medicine. 1987 Nov 26;     [PubMed PMID: 2891032]

[8]

Burgess E, Aluminum toxicity from oral sucralfate therapy. Nephron. 1991;     [PubMed PMID: 1758558]