Aminosalicylates

Key examples

• Mesalazine
• Sulfasalazine

 

Common indications

• Mesalazine is used first-line in the treatment of mild-to-moderate ulcerative colitis; sulfasalazine is an alternative but has largely been replaced by mesalazine for this indication.
• Sulfasalazine is one of several options for the management of rheumatoid arthritis, in which it is used as a disease-modifying antirheumatic drug (DMARD), usually as part of combination therapy.

 

Mechanisms of action

• In ulcerative colitis (UC), mesalazine and sulfasalazine both exert their therapeutic effects by releasing 5-aminosalicylic acid (5-ASA). The precise mechanism of action of 5-ASA is unknown, but it has both anti-inflammatory and immunosuppressive effects, and appears to act topically on the gut rather than systemically. For this reason, 5-ASA preparations are designed to delay delivery of the active ingredient to the colon. The oral form of mesalazine comprises a tablet with a coating that resists gastric breakdown, instead releasing 5-ASA further down the gut. Sulfasalazine consists of a molecule of 5-ASA linked to sulfapyridine. In the colon, bacterial enzymes break this link and release the two molecules. Sulfapyridine does not contribute to its therapeutic effect in UC, but it does cause side effects, and for this reason it has largely been replaced by mesalazine for this indication. By contrast, sulfapyridine is probably active in rheumatoid arthritis, though its mechanism is unclear. Mesalazine has no role in rheumatoid arthritis.

 

Important adverse effects

• Mesalazine generally causes fewer side effects than sulfasalazine. Most commonly, these are gastrointestinal upset (e.g. nausea, dyspepsia) and headache. Both drugs can cause rare but serious blood abnormalities (e.g. leucopenia, thrombocytopenia) and renal impairment. In men, sulfasalazine may induce a reversible decrease in the number of sperm (oligospermia). It can also cause a serious hypersensitivity reaction comprising fever, rash and liver abnormalities.

 

Warnings

• Mesalazine and sulfasalazine are salicylates, like aspirin. 
• Patients who have aspirin hypersensitivity should not take these drugs.

 

Important interactions

• Mesalazine tablets with a pH-sensitive coating (e.g. Asacol® MR) may interact with drugs that alter gut pH. 
• For example, proton pump inhibitors increase gastric pH so may cause the coating to be broken down prematurely. 
• Lactulose lowers stool pH and may prevent 5-ASA release in the colon.