Sulfasalazine


Sulfasalazine, sold under the trade name Azulfidine among others, is a medication used to treat rheumatoid arthritis, ulcerative colitis, and Crohn's disease. It is considered by some to be a first line treatment in rheumatoid arthritis. It is taken by mouth.
Significant side effects occur in about 25% of people. Commonly these include loss of appetite, nausea, headache, and rash. Severe side effects include bone marrow suppression, liver problems, Stevens–Johnson syndrome, and kidney problems. It should not be used in people allergic to aspirin or sulfonamide. Use during pregnancy appears to be safe for the baby.
Sulfasalazine is in the disease-modifying antirheumatic drugs family of medications. It is unclear exactly how it works. One proposed mechanism is the inhibition of prostaglandins, resulting in local anti-inflammatory effects in the colon. The medication is broken down by intestinal bacteria into sulfapyridine and 5-aminosalicylic acid. That which is absorbed is excreted by the kidneys and in the bile.
Sulfasalazine was approved for medical use in the United States in 1950. It is on the World Health Organization's List of Essential Medicines, the safest and most effective medicines needed in a health system. Sulfasalazine is available as a generic medication and is cost effective with respect to inflammatory bowel disease as of 2017.

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.
It is usually not given to children under two years of age.

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.
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.
Sulfasalazine inhibits dihydropteroate synthase, and can cause folate deficiency and megaloblastic anemia. and various other undesirable effects.
Sulfasalazine can cause hemolytic anemia in people with G6PD deficiency.
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.
Sulfasalazine may cause sulfhemoglobinemia.

Pharmacology

Around 90% of a dose of sulfasalazine reaches the colon, where most of it is metabolized by bacteria into sulfapyridine and mesalazine. Both metabolites are active; most of the sulfapyridine is absorbed and then further metabolized, but most mesalazine is not, and remains in the colon.
A mix of unchanged, hydroxylated, and glucuronidated sulfapyridine is eliminated in urine, as is acetylated mesalazine and unmetabolized sulfasalazine.
The mechanism of action is not clear, but it appears that sulfasalazine and its metabolites have immunosuppressive, antibacterial, and anti-inflammatory effects. It also appears to inhibit the cystine-glutamate antiporter.

Chemistry

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

Cost

Use for rheumatoid arthritis cost about US$500 per year for sulfazalazine in the United States in 2002 versus up to $25,000 per year for TNF blocking agents. This was for a 2 gm per day dose of the 500 mg tablets. In the United States in 2020 the wholesale cost is 0.16 for the 500 mg immediate release tablets and 0.23 for the 500 mg slow release tablets. The wholesale cost in 4 countries in the developing world varies from 0.11 to 0.24 per 500 mg tablet as of 2015. The daily defined dose is 2 grams. It is commonly used in IBD in part due to its cost effectiveness.

Research

Sulfasalazine has been studied in cirrhosis, psoriasis, idiopathic urticaria, and amyloidosis.