Sucralfate

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: 

• Antipeptic effects: Sucralfate prevents hydrolysis by preventing the enzyme-substrate complex formation. This drug adsorbs pepsin and decreases its concentration.
• Site-protective effects: By forming a polyanion gel, sucralfate is a physical barrier between luminal contents and mucosa, protecting ulcers from acid and pepsin.
• Effects on mucus: Sucralfate increases mucous hydrophobicity, viscosity, sulfation, and aluminum and carbohydrate content, improving mucosal protection from acid. Additionally, sucralfate increases mucus production by increasing prostaglandin production and prevents the breakdown of mucus by pepsin A, thus reducing ulcerogenesis.
• Effect on bicarbonate output: Sucralfate increases prostaglandin-dependent and independent bicarbonate production by the stomach and duodenum. 
• Effects on tissue growth, regeneration, and repair: Sucralfate binds epidermal growth and tissue growth factors to tissues and facilitates repair.[2]

Pharmacokinetics 

Absorption: Only 5% of an orally administered dose is absorbed. The onset of action is 1 to 2 hours. The drug's duration of action is up to 6 hours.[9]

Distribution: Sucralfate is primarily distributed to lesions in the gastrointestinal tract.

Metabolism: Sucralfate is degraded to aluminum and sucrose octasulfate in the GI tract; the liver or kidney does not metabolize it.

Elimination: Small amounts of absorbed sulfated disaccharides are excreted in the urine.[10]

Administration

Available Dosage Forms and Strengths

Oral dosage forms 

Tablet: Sucralfate is a basic aluminum salt of sucrose octasulfate. When given orally, it disintegrates in the stomach with acid and binds to normal and damaged mucosa, forming a protective layer. In addition, it releases aluminum and binds to positively charged compounds like proteins, peptides, glycoproteins, and glycolipoproteins, including an adhesive layer protecting the mucosa; 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/5 mL. 

Rectal: According to the American Society of Colon and Rectal Surgeons, sucralfate retention enemas are an effective treatment for rectal bleeding resulting from chronic radiation proctitis.[11] Sucralfate tablets have been mixed with water to form a sucralfate paste enema: 2 tablets (2 g of sucralfate) mixed with 4.5 mL of water. This is an option in the treatment of hemorrhagic radiation proctitis. Sucralfate enema is also helpful in solitary rectal ulcer syndrome and diversion colitis.

Topical: Sucralfate is used topically in the treatment of skin conditions and also for mucosal ulcers.[12]

Adult Dosing

For active duodenal ulcers, the recommended adult dosage is 1 gram 4 times daily on an empty stomach. Treatment with sucralfate should be continued for 4 to 8 weeks. The maintenance dosage is 1 g twice daily. 

Specific Patient Populations 

Hepatic impairment: No information is provided in manufacturer labeling. Caution is advised. According to the American Association for the Study of Liver Diseases (AASLD), patients with an acute liver injury should receive PPI or H2 blockers for stress ulcer prophylaxis. However, sucralfate can also be considered.[13][14]

Renal impairment: Aluminum accumulation and toxicity have been documented due to sucralfate in patients with impaired renal function. Use with caution.[15]

Pregnancy considerations: Sucralfate is an FDA category B medication under the prior pregnancy classification system. Sucralfate has minimal systemic absorption. No significant maternal or fetal adverse effects have been marked; sucralfate is usually considered safe during pregnancy.[16]

Breastfeeding considerations: Clinical data regarding sucralfate use during breastfeeding are lacking. However, as sucralfate is minimally absorbed, it is considered safe during breastfeeding, and no precautions are necessary.[17]

Pediatric patients: The safety and efficacy of systemic sucralfate in pediatric patients have not been demonstrated. Use with caution. Topical sucralfate is used off-label in pediatric patients with adenotonsillectomy in the postoperative period to reduce oropharyngeal pain.[18]

Older patients: Caution is advised as sucralfate can reduce the absorption of other medications. In addition, renal function monitoring is recommended for older patients.[19]

Adverse Effects

Sucralfate acts locally with negligible absorption, making it relatively safe. The most common side effect is constipation, seen in 1% to 10% of patients. Hyperglycemia is also reported in diabetic patients using sucralfate. Other adverse effects include nausea, vomiting, flatulence, headache, dry mouth, pruritis, skin rash, gastric bezoar formation, aluminum intoxication, and 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 negligible levels of aluminum, 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 cautiously in patients with end-stage renal disease or avoided altogether to prevent aluminum intoxication.[2][20]

Drug-Drug Interactions

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 administering these medications. In addition, 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.

Concurrent administration of sucralfate decreases the bioavailability and concentration of phenytoin. Avoid simultaneous administration.[9]

Sucralfate may reduce the serum concentration of quinidine. Avoid concurrent administration.[21]

Sucralfate may also decrease the absorption or delay the onset of action of several drugs; some medications that are so affected include:

• Naproxen (delayed onset of action)
• Potassium phosphate
• Leveoketoconazole
• Deferasirox
• Baloxavir

Contraindications

Documented hypersensitivity to sucralfate or excipients is an absolute contraindication, as it can result in an anaphylactic reaction.[22] Relative contraindications include uncontrolled diabetes with hyperglycemia, impaired swallowing/gag reflex, and end-stage renal disease.[15] 

As discussed above, sucralfate has significant drug-drug interactions, so a complete medication reconciliation should be performed before initiating therapy.[9]

Monitoring

No therapeutic monitoring has been recommended for this medication as it undergoes minimal absorption from the enteral system. If the patient has diabetes, blood glucose monitoring may be necessary as the sucralfate oral suspension contains glucose. Renal function should be monitored in patients with a history of renal impairment.[15]

Toxicity

Risks associated with sucralfate overdosing are minimal as sucralfate has minimal absorption from the gastrointestinal system; many patients who 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.[15][23] Serum aluminum should be obtained in these patients, and treatment with deferoxamine and EDTA should be considered for aluminum toxicity.[24]

Enhancing Healthcare Team Outcomes

Managing the side effects of chemotherapy and radiation has become a challenge and is often encountered by clinicians with new treatment regimens that contribute to the 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, particularly with the move away from opioids. 

Interprofessional team coordination can take on several forms. MDs, DOs, NPs, or PAs will order or prescribe the medication. Nurses can provide patient counseling, coordinate refills, and serve as the contact point for the prescribing clinician. The pharmacist is tasked with checking the dosing and frequency of administration, providing additional patient counseling regarding how to use the medication, watching for potential adverse events, and contacting the prescriber with any concerns. Nurses will often administer the medication to inpatients and are in the best position to note any issues; they must report to the prescribing clinician and recommend changes in the patient's regimen.

Gastroenterologist consultation is required in patients with refractory peptic ulcer disease. Critical care physicians and toxicologists should be consulted for accidental overdose. These are just a few examples showing how interprofessional team coordination and information sharing will optimize patient outcomes.