Sulfasalazine

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Sulfasalazine
Clinical data
Trade namesAzulfidine, Salazopyrin, Sulazine, others
Other namesSulphasalazine
AHFS/Drugs.comMonograph
MedlinePlusa682204
Pregnancy
category
Routes of
administration		by mouth
ATC code
Pharmacokinetic data
Bioavailability<15%
Elimination half-life5-10 hours
Identifiers
  • 2-hydroxy-5-[(E)-2-{4-[(pyridin-2-yl)sulfamoyl]phenyl}diazen-1-yl]benzoic acid
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.009.069 Edit this at Wikidata
Chemical and physical data
FormulaC18H14N4O5S
Molar mass398.394 g/mol g·mol−1
3D model (JSmol)
  • O=S(=O)(Nc1ccccn1)c3ccc(/N=N/c2cc(C(O)=O)c(O)cc2)cc3
  • InChI=1S/C18H14N4O5S/c23-16-9-6-13(11-15(16)18(24)25)21-20-12-4-7-14(8-5-12)28(26,27)22-17-3-1-2-10-19-17/h1-11,23H,(H,19,22)(H,24,25) checkY
  • Key:NCEXYHBECQHGNR-UHFFFAOYSA-N checkY
 ☒NcheckY (what is this?)  (verify)

Sulfasalazine (SSZ), sold under the trade name Azulfidine among others, is a medication used to treat rheumatoid arthritis, ulcerative colitis, and Crohn's disease.[1] It is often considered as a first line treatment in rheumatoid arthritis.[2] It is taken by mouth.[1]

Significant side effects occur in about 25% of people.[2] Commonly these include loss of appetite, nausea, headache, and rash.[1] Severe side effects include bone marrow suppression, liver problems, and kidney problems.[2][3] It should not be used in people allergic to aspirin or sulfonamide.[2] Use during pregnancy appears to be safe for the baby.[1] Sulfasalazine is in the disease-modifying antirheumatic drugs (DMARDs) family of medications.[1] It is unclear exactly how it works but is broken down into sulfapyridine and 5-aminosalicylic acid.[1]

Sulfasalazine was approved for medical use in the United States in 1950.[1] It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system.[4] Sulfasalazine is available as a generic medication.[1] The wholesale cost in the developing world is about 9 to 33 USD a month.[5] In the United States it costs 25 to 50 USD per month.[3]

Medical uses

Sulfasalazine is used in the treatment of inflammatory bowel disease, including ulcerative colitis and Crohn's disease. It is also indicated for use in rheumatoid arthritis and used in other types of inflammatory arthritis (e.g. psoriatic arthritis and reactive arthritis).[6][7]

It is usually not given to children under 2 years of age.[7]

Side effects

Sulfasalazine metabolizes to sulfapyridine. Serum levels should be monitored every three months, and more frequently at the outset. Serum levels above 50 μg/l are associated with side effects. In rare cases, Sulfasalazine can cause severe depression in young males. It can also cause temporary infertility. Immune thrombocytopenia has been reported.[8]

Sulfasalazine inhibits dihydropteroate synthase, and can cause folate deficiency and megaloblastic anemia.[9][10][11] and various other undesirable effects.[12]

Sulfasalazine can cause hemolytic anemia in people with G6PD deficiency.[13]

Sulfasalazine may cause stomach upset, nausea, vomiting, loss of appetite, headache, dizziness, or unusual tiredness. Skin and urine can become orange, with occasional allergic reactions.[14]

Pharmacology

Around 90% of a dose of sulfasalazine reaches the colon, where most of it is metabolized by bacteria into sulfapyridine and mesalazine (also known as 5-aminosalicylic acid or 5-ASA). Both metabolites are active; most of the sulfapyridine is absorbed and then further metabolized, but most mesalazine is not, and remains in the colon.[7]

A mix of unchanged, hydroxylated, and glucuronidated sulfapyridine is eliminated in urine, as is acetylated mesalazine and unmetabolized sulfasalazine.[7]

The mechanism of action is not clear, but it appears that sulfasalazine and its metabolites have immunosuppressive, antibacterial, and anti-inflammatory effects.[6][7] It also appears to inhibit the cystine-glutamate antiporter.[15]

Research

Sulfasalazine has been studied in cirrhosis[16], idiopathic urticaria,[17] and amyloidosis.[18]

References

  1. ^ a b c d e f g h i "Sulfasalazine". The American Society of Health-System Pharmacists. Archived from the original on 21 December 2016. Retrieved 8 December 2016. {{cite web}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)
  2. ^ a b c d WHO Model Formulary 2008 (PDF). World Health Organization. 2009. p. 41,45. ISBN 9789241547659. Archived from the original (PDF) on 13 December 2016. Retrieved 8 December 2016. {{cite book}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)
  3. ^ a b Hamilton, Richart (2015). Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition. Jones & Bartlett Learning. p. 464. ISBN 9781284057560.
  4. ^ "WHO Model List of Essential Medicines (19th List)" (PDF). World Health Organization. April 2015. Archived from the original (PDF) on 13 December 2016. Retrieved 8 December 2016. {{cite web}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)
  5. ^ "Sulfasalazine". International Drug Price Indicator Guide. Archived from the original on 10 May 2017. Retrieved 8 December 2016. {{cite web}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)
  6. ^ a b "US Sulfasalazine label" (PDF). FDA. February 2014. Archived from the original (PDF) on 2017-02-16. {{cite web}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help) For updates see index page at FDA for NDA 007073 Archived 2017-04-16 at the Wayback Machine
  7. ^ a b c d e "Salazopyrin Tablets - Summary of Product Characteristics". UK Electronic Medicines Compendium. February 2014. Archived from the original on 2017-04-16. {{cite web}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)
  8. ^ Cantarini L, Tinazzi I, Biasi D, Fioravanti A, Galeazzi M (June 2007). "Sulfasalazine-induced immune thrombocytopenia". Postgraduate Medical Journal. 83 (980): e1. doi:10.1136/pgmj.2006.055194. PMC 2600053. PMID 17551063.
  9. ^ Inflammatory Bowel Disease~workup at eMedicine
  10. ^ Women With Autoimmune Diseases: Medications During Pregnancy and Lactation: Sulfasalazine; "Archived copy". Archived from the original on 2011-10-21. Retrieved 2012-03-08. {{cite web}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)CS1 maint: archived copy as title (link)
  11. ^ Hernández-Díaz, Sonia; Werler, Martha M.; Walker, Alexander M.; Mitchell, Allen A. (2000). "Folic Acid Antagonists during Pregnancy and the Risk of Birth Defects". New England Journal of Medicine. 343 (22): 1608–14. doi:10.1056/NEJM200011303432204. PMID 11096168.
  12. ^ Dixon, Scott J; Patel, Darpan N; Welsch, Matthew; Skouta, Rachid; Lee, Eric D; Hayano, Miki; Thomas, Ajit G; Gleason, Caroline E; Tatonetti, Nicholas P (2014-05-20). "Pharmacological inhibition of cystine–glutamate exchange induces endoplasmic reticulum stress and ferroptosis". eLife. 3. doi:10.7554/eLife.02523. ISSN 2050-084X. PMC 4054777. PMID 24844246.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  13. ^ "SulfaSALAzine: Drug Information Provided by Lexi-Comp". Merck & Co., Inc. Jan 2012. Archived from the original on 2011-08-29. Retrieved 2012-07-28. {{cite web}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)
  14. ^ "DRUGS & MEDICATIONS Sulfasalazine". WebMD. WebMD. Archived from the original on 2016-01-26. {{cite web}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)
  15. ^ Bridges, Richard J; Natale, Nicholas R; Patel, Sarjubhai A (2012-01-01). "System xc- cystine/glutamate antiporter: an update on molecular pharmacology and roles within the CNS". British Journal of Pharmacology. 165 (1): 20–34. doi:10.1111/j.1476-5381.2011.01480.x. ISSN 0007-1188. PMC 3252963. PMID 21564084.
  16. ^ Fiona Oakley; Muriel Meso; John P. Iredale; Karen Green; Carylyn J. Marek; Xiaoying Zhou; Michael J. May; Harry Millward-Sadler; Matthew C. Wright; Derek A. Mann (Jan 2005). "Inhibition of inhibitor of κB kinases stimulates hepatic stellate cell apoptosis and accelerated recovery from rat liver fibrosis". Gastroenterology. 128 (1): 108–120. doi:10.1053/j.gastro.2004.10.003.
  17. ^ McGirt LY, Vasagar K, Gober LM, Saini SS, Beck LA (Oct 2006). "Successful treatment of recalcitrant chronic idiopathic urticaria with sulfasalazine". Arch Dermatol. 142 (10): 1337–1342. doi:10.1001/archderm.142.10.1337. PMID 17043190.
  18. ^ Brumshtein B, Esswein SR, Salwinski L, Phillips ML, Ly AT, Cascio D, Sawaya MR, Eisenberg DS (Nov 2015). "Inhibition by small-molecule ligands of formation of amyloid fibrils of an immunoglobulin light chain variable domain". eLIFE. 4: e10935. doi:10.7554/eLife.10935. PMID 26576950.{{cite journal}}: CS1 maint: unflagged free DOI (link)

External links

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