Sulfasalazine

Sulfasalazine, sold under the brand name Azulfidine among others, is a medication used to treat rheumatoid arthritis, ulcerative colitis, and Crohn's disease.<ref name=AHFS2016/> It is considered by some to be a first-line treatment in rheumatoid arthritis.<ref name=WHO2008/> It is taken by mouth or can be administered rectally.<ref name=AHFS2016/>

Significant side effects occur in about 25% of people.<ref name=WHO2008/> Commonly these include loss of appetite, nausea, headache, and rash.<ref name=AHFS2016/> Severe side effects include bone marrow suppression, liver problems, Stevens–Johnson syndrome, and kidney problems.<ref name=WHO2008/><ref name=Ric2015>Template:Cite book</ref><ref name=Dav2014>Template:Cite book</ref> It should not be used in people allergic to aspirin or sulfonamide.<ref name=WHO2008>Template:Cite book</ref> Use during pregnancy appears to be safe for the baby.<ref name=AHFS2016/>

Sulfasalazine is in the disease-modifying antirheumatic drugs (DMARDs) family of medications.<ref name=AHFS2016/> It is unclear exactly how it works.<ref name=AHFS2016/> One proposed mechanism is the inhibition of prostaglandins, resulting in local anti-inflammatory effects in the colon.<ref name=Dav2014 /> The medication is broken down by intestinal bacteria into sulfapyridine and 5-aminosalicylic acid.<ref name="AHFS2016" />

Sulfasalazine was approved for medical use in the United States in 1950.<ref name=AHFS2016>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> It is on the World Health Organization's List of Essential Medicines.<ref name="WHO21st">Template:Cite book</ref> Sulfasalazine is available as a generic medication.<ref name=AHFS2016/> In 2020, it was the 284th most commonly prescribed medication in the United States, with more than 1Template:Nbspmillion prescriptions.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

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).<ref name=USlabel2014>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref name=UKlabel2014>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref name="UK sulfasalazine label" />

It is usually not given to children under two years of age.<ref name=UKlabel2014/><ref name="UK sulfasalazine label" />

Side effects

Use of sulfasalazine is contraindicated in people with sulfa allergies and in those with urinary tract obstructions, intestinal obstructions, and severe liver or kidney problems.<ref name=Dav2014 />

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 oligospermia and temporary infertility. Immune thrombocytopenia has been reported.<ref name="pmid17551063">Template:Cite journal</ref>

Sulfasalazine inhibits dihydropteroate synthase, and can cause folate deficiency and megaloblastic anemia.<ref>Template:EMedicine</ref><ref>Women With Autoimmune Diseases: Medications During Pregnancy and Lactation: Sulfasalazine; {{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>Template:Cite journal</ref> and various other undesirable effects.<ref>Template:Cite journal</ref>

Sulfasalazine can cause hemolytic anemia in people with G6PD deficiency.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Sulfasalazine can cause kidney stones.<ref>Template:Cite journal</ref> Sulfasalazine may cause stomach upset, nausea, vomiting, loss of appetite, headache, dizziness, or unusual tiredness.<ref name=AHFS2016/> Skin and urine can become orange, with occasional allergic reactions.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref name=AHFS2016/>

Sulfasalazine may cause sulfhemoglobinemia.Template:Citation needed

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.<ref name=UKlabel2014/>

A mix of unchanged, hydroxylated, and glucuronidated sulfapyridine is eliminated in urine, as is acetylated mesalazine and unmetabolized sulfasalazine.<ref name=UKlabel2014/><ref name="UK sulfasalazine label" />

The mechanism of action is not clear, but it appears that sulfasalazine and its metabolites have immunosuppressive, antibacterial, and anti-inflammatory effects.<ref name=USlabel2014/><ref name=UKlabel2014/> It also appears to inhibit the cystine-glutamate antiporter,<ref>Template:Cite journal</ref> as well as sepiapterin reductase.<ref name="pmid22178186">Template:Cite journal</ref>

Chemistry

It is a codrug which is a combination of sulfapyridine and 5-aminosalicylic acid coupled with an azo linkage.

Cost

In people with rheumatoid arthritis, the cost-effectiveness of sulfasalazine is improved by combining it with other drugs.<ref>Template:Cite journal</ref> It is commonly used in treating inflammatory bowel disease in part due to its cost effectiveness.<ref name="Bau2017">Template:Cite book</ref>

Research

Sulfasalazine has been studied in cirrhosis,<ref name=Oakely2005>Template:Cite journal</ref> psoriasis,<ref name=Aditya1990>Template:Cite journal</ref> idiopathic urticaria,<ref name="pmid17043190">Template:Cite journal</ref> and amyloidosis.<ref name="pmid26576950">Template:Cite journal</ref>