Sucralfate

Sucralfate

Clinical data
Trade names	Carafate
AHFS/Drugs.com	Monograph
MedlinePlus	a681049
Pregnancy category	B
Routes of administration	oral, suspension, rectal suspension
ATC code	A02BX02 (WHO)
Legal status
Legal status	℞ (Prescription only)
Pharmacokinetic data
Bioavailability	3-5% (local acting)
Metabolism	GI; liver: unknown
Biological half-life	unknown
Excretion	feces, urine
Identifiers
IUPAC name Hexadeca-μ-hydroxytetracosahydroxy[μ8-[1,3,4,6-tetra-O-sulfo-β-Dfructofuranosyl-α-D-glucopyranoside tetrakis(hydrogen sulfato)8-)]]hexadecaaluminum[1]
CAS Number	54182-58-0
PubChem (CID)	6398525
DrugBank	DB00364
ChemSpider	4911161
UNII	XX73205DH5
ChEMBL	CHEMBL611727
ECHA InfoCard	100.053.636
Chemical and physical data
Formula	C12H54Al16O75S8
Molar mass	2086.75 g/mol[1]
(what is this?)  (verify)

Sucralfate is a medication primarily taken to treat active duodenal ulcers.^[2] Sucralfate is also used for the treatment of gastroesophageal reflux disease (GERD) and stress ulcers.^[3]

Sucralfate is a sucrose sulfate-aluminium complex that binds to the ulcer, creating a physical barrier that protects the gastrointestinal tract from stomach acid and prevents the degradation of mucus.^[4][5] It also promotes bicarbonate production and acts like an acid buffer with cytoprotective properties.^[6]

Medical uses

Sucralfate is used for the treatment of active duodenal ulcers not related to the use of nonsteroidal anti-inflammatory drugs (NSAIDs), as the mechanism behind these ulcers is due to acid oversecretion.^[2] It is not FDA approved for gastric ulcers, as the main mechanism is not due to acid oversecretion but rather from diminished protection. The use for sucralfate in peptic ulcer disease has diminished recently, but it is still the preferred agent for stress ulcer prevention.^{[7][8][9][10]}

Sucralfate has also been used for the following conditions:

• Active duodenal ulcer not related to NSAID use
• Maintenance therapy for resolved duodenal ulcers
• Gastric ulcer not related to NSAID use and gastritis due to GERD. Triple combination therapy with lansoprazole + cisapride + sucralfate can significantly improve symptoms and quality of life and was more cost-effective than ranitidine combination group.^[11]
• Aphthous ulcer and stomatitis due to radiation or chemotherapy
• Proctitis from radiation or ulcerative colitis^[12]
• Gastro-esophageal reflux disease during pregnancy -- first-line drug therapy combined with lifestyle and diet modification.^[13]
• Stress ulcer prophylaxis—The use of sucralfate rather than H₂ antagonists for stress ulcer prophylaxis, and measures to prevent aspiration, such as continuous subglottic suctioning, have been shown to reduce the risk of ventilator-associated pneumonia (VAP).^[14]
• Prevention of stricture formation—sucralfate has an inhibitory effect on stricture formation in experimental corrosive burns and can be used in the treatment of corrosive esophageal burns to enhance mucosal healing and suppress stricture formation^[15]
• Rectal bleeding and its management after irradiation for uterine cervical cancer
  • Grade 1 bleeding experienced immediate relief with sucrasulfate enema for 1 month.
  • Grade 2 bleeding, sucrasulfate enema and/or coagulation were effective.
  • Grade 3 bleeding lasted for 1 year despite frequent transfusions and coagulation.
  • Grade 2 and 3 rectal bleeding occurred in 8.5% of people. The most significant risk factor was the ICRU-CRBED. Prompt treatment with a combination of sucrasulfate enema and coagulation is effective in controlling Grade 1 and 2 rectal bleeding without the development of fistula or stricture.^[16]
• Treatment of anastomotic ulcer after Gastric bypass surgery

Side effects

The most common side effect seen is constipation (2-3%). Less commonly reported side effects (<0.5%) include flatulence, headache, hypophosphatemia, xerostomia (dry mouth), and bezoar formation.^[17][18][19] Avoid using this drug in people with chronic kidney failure, as it might cause aluminium accumulation and toxicity. There is a limited number of well-controlled studies investigating the safety and efficacy of sucralfate in children and pregnant women (Pregnancy Category B).^[2][20][21]

Mechanism of action

Sucralfate is a locally acting substance that in an acidic environment (pH < 4) reacts with hydrochloric acid in the stomach to form a cross-linking, viscous, paste-like material capable of acting as an acid buffer for as long as 6 to 8 hours after a single dose.^[4] It also attaches to proteins on the surface of ulcers, such as albumin and fibrinogen, to form stable insoluble complexes. These complexes serve as protective barriers at the ulcer surface, preventing further damage from acid, pepsin, and bile.^[4] In addition, sucralfate prevents back diffusion of hydrogen ions, and adsorbs both pepsin and bile acids.

Recently, it has been thought that sucralfate also stimulates the production of prostaglandin E₂, epidermal growth factors (EGF), bFGF, and gastric mucus.^[2][5]

Pharmacokinetics

Onset: 1-2 hr (initial onset for peptic ulcer disease (PUD))

Absorption: <5% Orally

Duration: Up to 6 hours due to high affinity for defective mucosa (PUD)

Bioavailability: 5% as sucralfate is considered non-systemic, sucrose octasulfate: 5%, aluminum:0.005%

Metabolism: Not metabolized, excreted unchanged in urine

Excretion: Primarily in urine as unchanged drug^[21][22]

Names

Brand names include Carafate in U.S.A., Sucramal in Italy, Sucrafil, Sufrate, Sucralpro, Sucralcoat, Pepsigard, Sucral, Hapifate in India, Sutra or Musin in parts of South-East Asia, Sulcrate in Canada, Ulsanic in South Africa and Israel, Andapsin in Sweden and Antepsin in Turkey.

References

1. Merck Index, 12th Edition, 9049.
2. "DailyMed - CARAFATE - sucralfate suspension". dailymed.nlm.nih.gov. Retrieved 2015-11-04.
3. Maton PN (2003). "Profile and assessment of GERD pharmacotherapy". Cleve Clin J Med. 70 Suppl 5: S51–70. doi:10.3949/ccjm.70.Suppl_5.S51. PMID 14705381.
4. Brogden, R. N.; Heel, R. C.; Speight, T. M.; Avery, G. S. (1984-03-01). "Sucralfate. A review of its pharmacodynamic properties and therapeutic use in peptic ulcer disease". Drugs. 27 (3): 194–209. doi:10.2165/00003495-198427030-00002. ISSN 0012-6667. PMID 6368184.
5. Korman, M. G.; Bolin, T. D.; Szabo, S.; Hunt, R. H.; Marks, I. N.; Glise, H. (1994-08-01). "Sucralfate: the Bangkok review". Journal of Gastroenterology and Hepatology. 9 (4): 412–415. doi:10.1111/j.1440-1746.1994.tb01264.x. ISSN 0815-9319. PMID 7948825.
6. Lam, Shiu Kum; Ching, Chi Kong (1994). "Sucralfate in clinical practice". Journal of Gastroenerology and Hepatology. 9 (4).
7. Hunt, R. H. (1991-08-08). "Treatment of peptic ulcer disease with sucralfate: a review". The American Journal of Medicine. 91 (2A): 102S–106S. ISSN 0002-9343. PMID 1882894.
8. Fashner, Julia; Gitu, Alfred C. (2015-02-15). "Diagnosis and Treatment of Peptic Ulcer Disease and H. pylori Infection". American Family Physician. 91 (4): 236–242. ISSN 1532-0650. PMID 25955624.
9. "ASHP Therapeutic Guidelines on Stress Ulcer Prophylaxis. ASHP Commission on Therapeutics and approved by the ASHP Board of Directors on November 14, 1998". American Journal of Health-System Pharmacy. 56 (4): 347–379. 1999-02-15. ISSN 1079-2082. PMID 10690219.
10. Monnig, Andrea A.; Prittie, Jennifer E. (2011-10-01). "A review of stress-related mucosal disease". Journal of Veterinary Emergency and Critical Care (San Antonio, Tex.: 2001). 21 (5): 484–495. doi:10.1111/j.1476-4431.2011.00680.x. ISSN 1476-4431. PMID 22316196.
11. Jian-Min, Si; Liang-Jing, Wang; Shu-Jie, Chen; Lan, Zhao; Ning, Dai (2003). "Quality of life and cost-effectiveness of combined therapy for reflux esophagitis". Journal of Zhejiang University SCIENCE A. 4 (5): 602–6. doi:10.1631/jzus.2003.0602. PMID 12958722.
12. Mendenhall, William M.; McKibben, Brian T.; Hoppe, Bradford S.; Nichols, Romaine C.; Henderson, Randal H.; Mendenhall, Nancy P. (2014-10-01). "Management of radiation proctitis". American Journal of Clinical Oncology. 37 (5): 517–523. doi:10.1097/COC.0b013e318271b1aa. ISSN 1537-453X. PMID 23241500.
13. Richter, J. E. (2005-11-01). "Review article: the management of heartburn in pregnancy". Alimentary Pharmacology & Therapeutics. 22 (9): 749–757. doi:10.1111/j.1365-2036.2005.02654.x. ISSN 0269-2813. PMID 16225482.
14. Safdar, Nasia; Crnich, Christopher J.; Maki, Dennis G. (2005-06-01). "The pathogenesis of ventilator-associated pneumonia: its relevance to developing effective strategies for prevention". Respiratory Care. 50 (6): 725–739; discussion 739–741. ISSN 0020-1324. PMID 15913465.
15. Temir, Z. Günyüz; Karkiner, Aytaç; Karaca, Irfan; Ortaç, Ragip; Ozdamar, Aykut (2005-01-01). "The effectiveness of sucralfate against stricture formation in experimental corrosive esophageal burns". Surgery Today. 35 (8): 617–622. doi:10.1007/s00595-004-3005-0. ISSN 0941-1291. PMID 16034539.
16. Chun, Mison; Kang, Seunghee; Kil, Hoon-Jong; Oh, Young-Taek; Sohn, Jeong-Hye; Ryu, Hee-Suk (2004-01-01). "Rectal bleeding and its management after irradiation for uterine cervical cancer". International Journal of Radiation Oncology, Biology, Physics. 58 (1): 98–105. doi:10.1016/s0360-3016(03)01395-6. ISSN 0360-3016. PMID 14697426.
17. http://medsfacts.com/study-SUCRALFATE-causing-BEZOAR.php
18. "Carafate Package Insert" (PDF). September 12, 2013. Retrieved November 2, 2015.
19. "ASHP Therapeutic Guidelines on Stress Ulcer Prophylaxis. ASHP Commission on Therapeutics and approved by the ASHP Board of Directors on November 14, 1998". American Journal of Health-System Pharmacy. 56 (4): 347–379. 1999-02-15. ISSN 1079-2082. PMID 10690219.
20. Phupong, Vorapong; Hanprasertpong, Tharangrut (2015-01-01). "Interventions for heartburn in pregnancy". The Cochrane Database of Systematic Reviews. 9: CD011379. doi:10.1002/14651858.CD011379.pub2. ISSN 1469-493X. PMID 26384956.
21. Steiner, K.; Bühring, K. U.; Faro, H. P.; Garbe, A.; Nowak, H. (1982-01-01). "Sucralfate: pharmacokinetics, metabolism and selective binding to experimental gastric and duodenal ulcers in animals". Arzneimittel-Forschung. 32 (5): 512–518. ISSN 0004-4172. PMID 6896647.
22. McEvoy, GK (2007). AHFS drug information McEvoy GK, ed. Sucralfate. AHFS. pp. 2983–5.

External links

• Medline Plus
• Medicine Net
• Rx List
• Drugs.com
• Kyoto Encyclopedia of Genes and Genomes
• Carafate prescribing information