What is mesalamine?

What is Mesalamine

Mesalamine (5-aminosalicylic acid or 5-ASA) is an anti-inflammatory medication used primarily to treat ulcerative colitis and, to a lesser extent, Crohn's disease, working through topical anti-inflammatory effects on the intestinal lining. 1, 2

Chemical Structure and Basic Properties

• Mesalamine is 5-amino-2-hydroxybenzoic acid with a molecular weight of 153.14 1
• It is the active therapeutic component of sulfasalazine, but without the sulfa carrier molecule that causes most adverse effects 3, 4

Mechanism of Action

• Mesalamine exerts a topical anti-inflammatory effect on colonic epithelial cells, though the complete mechanism is not fully understood 1, 2
• It blocks cyclooxygenase and inhibits prostaglandin production in the colon, reducing mucosal production of arachidonic acid metabolites 1, 2
• The drug also modulates leukotriene synthesis and affects cytokines and reactive oxygen species 5

Pharmacokinetics and Drug Delivery

• Only approximately 21-22% of the administered dose is absorbed systemically, with most remaining in the intestinal lumen to provide topical effects 5, 1, 2
• Delayed-release formulations are coated with pH-dependent polymer films that dissolve at pH ≥6.0-6.8, typically in the terminal ileum, allowing drug release in the colon 6, 1, 2
• Plasma concentrations become detectable after 2 hours and reach maximum levels at 9-12 hours post-administration 1, 2
• The poor systemic absorption and high local concentrations explain why topical formulations (suppositories, enemas) are often more effective than oral therapy for distal disease 5

Clinical Indications

Ulcerative Colitis (Primary Use)

• For active mild-to-moderate ulcerative colitis: Higher doses of 4 g/day orally are more effective than placebo, with clinical improvement occurring at twice the remission rate 7
• For ulcerative proctitis: Mesalamine 1 g suppository once daily is the preferred first-line treatment, superior to topical steroids 7, 8
• For maintenance of remission: Mesalamine 2 g/day reduces relapse rates 7
• Topical mesalamine is more effective than oral alone for distal disease, and combination therapy (topical plus oral) is superior to either alone 7, 8

Crohn's Disease (Limited Role)

• For active Crohn's ileocolitis, Pentasa 4 g daily shows modest benefit (mean CDAI reduction of 263 points vs 245 for placebo, p=0.04), though clinical significance is unclear 7
• Mesalamine 2 g/day reduces post-surgical relapse after small bowel resection (40% reduction at 18 months, NNT=8) 7
• It is ineffective for maintaining remission after steroid-induced remission, except in high-risk patients given 4 g/day 7
• The benefits in Crohn's disease are questionable compared to ulcerative colitis, and alternative treatments are usually more appropriate 4

Dosing Regimens

• Active ulcerative colitis: 4 g/day orally for induction 7
• Maintenance therapy: 1.5-2.4 g/day orally 6, 3
• Proctitis: 1 g suppository once daily 7, 8
• Left-sided colitis: Combination of topical 1 g daily plus oral 2-4 g daily 8
• Once-daily dosing is as effective as divided doses for topical therapy 7

Adverse Effects

• Common side effects include headache (2%), nausea (2%), diarrhea (3%), and rash (1%) 7, 5
• Paradoxical worsening of diarrhea occurs in approximately 3% of patients and may resemble a colitis flare with bloody diarrhea; recurrence on rechallenge confirms the diagnosis 7, 9
• Rare but serious idiosyncratic reactions include Stevens-Johnson syndrome, pancreatitis, agranulocytosis, alveolitis, interstitial nephritis, and nephrotic syndrome 7, 5
• Blood dyscrasias (agranulocytosis, neutropenia, pancytopenia) occur more frequently in patients ≥65 years old 1, 2
• Overall, mesalamine is well tolerated by approximately 85% of patients who are intolerant to sulfasalazine 3

Monitoring Requirements

• Evaluate renal function before initiation and periodically during therapy, as mesalamine is substantially excreted by the kidney 1, 2
• Monitor complete blood counts and platelet counts, especially in elderly patients 1, 2
• Discontinue if renal function deteriorates during treatment 1, 2

Important Clinical Considerations

• Mesalamine is substantially excreted by the kidney, and toxic reactions are more likely in patients with impaired renal function 1, 2
• Systemic exposures are increased in elderly subjects; consider starting at the low end of the dosing range 1, 2
• The medication has no role in maintenance therapy for Crohn's disease in most cases 7
• Suppositories are more appropriate than enemas for proctitis as they better target the rectum and are better tolerated 7
• Combination oral and topical therapy maximizes local drug exposure for distal disease 5