Aminosalicylates

Aminosalicylates deliver 5-aminosalicylic acid (mesalazine) to the colonic mucosa, where it reduces local inflammation. They are first-line for inducing and maintaining remission in mild to moderate ulcerative colitis and have little role in Crohn disease.

Mechanism. Topical inhibition of cyclo-oxygenase and lipoxygenase products, scavenging of free radicals and activation of PPAR-gamma. Benefit depends on drug reaching the diseased mucosa, not on blood levels.

Pharmacokinetics. Mesalazine given alone is absorbed in the upper gut, so oral forms use pH-dependent, time-dependent or matrix release to reach the colon. Sulfasalazine, balsalazide and olsalazine are prodrugs split by colonic bacteria.

• Mesalazine oral: induction 2.4 to 4.8 g daily; maintenance 1.6 to 2.4 g daily, once daily dosing being as effective as divided dosing.
• Mesalazine rectal: suppository 1 g daily for proctitis; enema 1 to 4 g at night for left-sided disease.
• Sulfasalazine 1 g four times daily for induction; 2 g daily for maintenance, with folic acid 5 mg daily.
• Balsalazide 2.25 g three times daily for induction; 2.25 g twice daily for maintenance.
• Olsalazine 500 mg twice daily, increased to 1 g three times daily.

Differences. Sulfasalazine is cheap and also treats inflammatory arthritis, but the sulfapyridine moiety causes most of its adverse effects. Mesalazine formulations are broadly equivalent. Olsalazine commonly causes diarrhoea.

• Proctitis: mesalazine suppository 1 g daily.
• Left-sided or extensive ulcerative colitis: oral mesalazine plus rectal mesalazine; the combination works better than either alone.
• Maintenance: lowest effective dose; continue long term.
• Crohn disease: limited value; sulfasalazine may help mild colonic disease.

Selection. Reassess at 4 weeks; if no response, add a corticosteroid and escalate.

Contraindications. Salicylate hypersensitivity, severe kidney impairment (creatinine clearance under 30 mL/min), severe liver impairment, and children under 2 years. Sulfasalazine in sulphonamide allergy and, with caution, G6PD deficiency.

Adverse effects. Headache, nausea, abdominal pain, rash. Acute intolerance with worsening colitis, interstitial nephritis, pancreatitis, hepatitis, pericarditis, myocarditis and pneumonitis. Sulfasalazine adds blood dyscrasias (agranulocytosis), haemolysis in G6PD deficiency, Stevens-Johnson syndrome, and reversible male oligospermia.

Interactions. Thiopurines (mesalazine inhibits thiopurine methyltransferase and may increase myelosuppression), warfarin (sulfasalazine), digoxin (absorption reduced by sulfasalazine), methotrexate.

Special groups.

• Pregnancy: mesalazine acceptable at the lowest effective dose; sulfasalazine acceptable with folic acid 5 mg daily before conception and throughout pregnancy.
• Breastfeeding: acceptable; infant diarrhoea is occasional; with sulfasalazine, avoid in jaundiced, premature or G6PD deficient infants.
• Children: weight-based specialist dosing.
• Older adults: monitor kidney function closely.
• Kidney impairment: avoid in advanced impairment.
• Male fertility: sulfasalazine impairs sperm count; switch to mesalazine when conceiving.

Monitoring. Creatinine and urinalysis at baseline, at 3 months, then yearly. For sulfasalazine, full blood count and liver enzymes monthly for 3 months, then every 3 months.

Referral and escalation. No response after 4 weeks of optimised oral and rectal therapy, severe bloody diarrhoea, fever or tachycardia (acute severe colitis), or unexplained rise in creatinine.