Sulfasalazine

Structural formula
General
Non-proprietary name	Sulfasalazine
other names	Salazosulfapyridine; 2-Hydroxy-5 - [( E ) -4- (pyridin-2-ylsulfamoyl) phenyldiazenyl] benzoic acid ( IUPAC ); 5- [4- (2-pyridylsulfamoyl) phenylazo] salicylic acid;
Molecular formula	C 18 H 14 N 4 O 5 S
External identifiers / databases
EC number	209-974-3
ECHA InfoCard	100.009.069
PubChem	5353980
DrugBank	DB00795
Wikidata	Q420035
Drug information
ATC code	A07 EC01
Drug class	Intestinal anti-inflammatory
properties
Molar mass	398.39 g · mol -1
Physical state	firmly
Melting point	220 ° C (decomposition)
safety instructions
	Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances danger
H and P phrases	H: 317-334
	P: 261-280-284-304 + 340-333 + 313-342 + 311
Toxicological data	15.6 g kg −1 ( LD 50 , rat , oral ) ; 12.5 g kg −1 ( LD 50 , mouse , oral ) ; 3.2 g kg −1 31 D −1 ( LD Lo , human , oral ) ;
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Sulfasalazine ( INN ) or salazosulfapyridine is an anti-inflammatory drug that is used in particular to treat chronic inflammatory bowel disease . Examples include Crohn's disease or ulcerative colitis , but also chronic polyarthritis . Chemically, it is a compound of the sulfonamide sulfapyridine with 5-aminosalicylic acid (5-ASA, also called mesalazine ).

Salazosulfapyridine is an inactive pro-drug and (taken orally) is only split into its active components sulfapyridine and 5-ASA by colon bacteria. Therefore, it can only work in the colon. The prodrug effect prevents the substance from being absorbed in the small intestine, which means that no effective amount can reach the large intestine.

Mode of action

The prodrug sulfasalazine is partially absorbed in the upper small intestine ( jejunum ), but a larger part is only split into sulfapyridine and 5-aminosalicylic acid in the colon by the bacterial enzyme azoreductase. The sulfonamide sulfapyridine itself is also anti-inflammatory and is used to treat rheumatoid arthritis, but is also responsible for a large part of the side effects of sulfasalazine. The 5-aminosalicylic acid has an anti-inflammatory effect by inhibiting the arachidonic acid metabolism , as a radical scavenger and by inhibiting the immune system. The individual mechanisms are detailed in the article on 5-ASA .

application areas

Salazosulfapyridine is mainly used in the acute treatment and prevention of recurrence of ulcerative colitis. But also with Crohn's disease, here it is mainly used for colon involvement. Another area of application is in joint diseases ( arthropathies ), which typically occur as side effects of chronic inflammatory bowel diseases. After all, it is also considered a basic therapeutic agent for chronic polyarthritis.

Side effects

Depending on the dose of the drug, nausea, vomiting, loss of appetite, decreased absorption of the vitamin folic acid and headaches can occur. Irrespective of the dose, changes in the blood count with a reduction in white blood cells ( leukocytes ), a shortened lifespan and increased breakdown of the red blood cells ( hemolytic anemia ) or a decrease in the number of blood platelets ( thrombocytopenia ) often occur . In rare cases, these side effects result in a threatening complete disappearance of the so-called granulocytes ( agranulocytosis ) or a complete failure of the bone marrow . Common side effects also include skin rashes, which can rarely turn into Stevens-Johnson syndrome , abdominal pain, nausea and vomiting, and increases in liver enzymes, which in turn can rarely be an expression of hepatitis .

Fertility

In women, is fertility is not affected by the medication of sulfasalazine. In men, the preparation can impair the mobility of the sperm. The number of sperm cells also appears to be reduced during therapy. It is therefore possible that men are unable to reproduce during sulfasalazine therapy. However, this normalizes 2–3 months after the drug is stopped.

Pregnancy, breastfeeding and the desire to have children

Women should definitely take folic acid before or after a pregnancy has occurred under the medication of sulfasalazine. Sulfasalazine appears to decrease folic acid absorption. Breastfeeding is not advised.

Trade names

Monopreparations

Azulfidine (D), Azulfidine RA (D), Colo-Pleon (D), Pleon RA (D), Salazopyrin (A, CH), various generics (D, A)

Individual evidence

↑ ^a ^b ^c ^d Entry on sulfasalazine in the ChemIDplus database of the United States National Library of Medicine (NLM) .
↑ ^a ^b ^c data sheet Sulfasalazine ≥ 98% from Sigma-Aldrich , accessed on May 13, 2017 ( PDF ).
^ Drugs in Japan. P. 420, 1990.
^ Journal of the Royal Society of Medicine. Vol. 73, p. 587, 1980.
↑ ^a ^b German Society for Rheumatology eV . (As of July 1, 2008).
↑ HE Langer: As a man, do I have to stop sulfasalazine before I plan to have children . As of November 21, 2006.

[chemid-1] Entry on sulfasalazine in the ChemIDplus database of the United States National Library of Medicine (NLM) .

[Sigma-2] ta sheet Sulfasalazine ≥ 98% from Sigma-Aldrich , accessed on May 13, 2017 ( PDF ).

[3] Drugs in Japan. P. 420, 1990.

[4] Journal of the Royal Society of Medicine. Vol. 73, p. 587, 1980.

[dgrh.de-2544-5] German Society for Rheumatology eV . (As of July 1, 2008).

[6] HE Langer: As a man, do I have to stop sulfasalazine before I plan to have children . As of November 21, 2006.