Introduction
Mesalamine (also known as mesalazine or 5-aminosalicylic acid) is an anti-inflammatory medication primarily used in the management of inflammatory bowel diseases. As a first-line therapy for mild to moderate ulcerative colitis, mesalamine represents a cornerstone treatment that directly targets colonic inflammation with minimal systemic absorption. This aminosalicylate compound has revolutionized IBD management since its introduction, offering effective mucosal healing with a favorable safety profile.
Mechanism of Action
Mesalamine exerts its therapeutic effects through multiple anti-inflammatory mechanisms within the gastrointestinal tract. The drug acts locally on the colonic mucosa to inhibit cyclooxygenase and lipoxygenase pathways, reducing prostaglandin and leukotriene production. Additionally, mesalamine scavenges reactive oxygen species, inhibits neutrophil chemotaxis and mast cell degranulation, and interferes with cytokine production (particularly IL-1 and TNF-α). Through these actions, mesalamine reduces mucosal inflammation and promotes tissue healing without significant systemic immunosuppression.
Indications
- Treatment of mildly to moderately active ulcerative colitis
- Maintenance of remission in ulcerative colitis
- Mild to moderate Crohn's disease (although less commonly used than for UC)
- Proctosigmoiditis and proctitis
Dosage and Administration
Ulcerative Colitis (Active Disease):- Oral: 2.4-4.8 g/day in divided doses
- Rectal: 1-4 g daily depending on formulation (enema or suppository)
- Oral: 1.5-4.8 g/day in divided doses
- Rectal: 500 mg suppository twice daily or 1 g nightly
- Renal impairment: Use with caution; contraindicated in severe impairment
- Hepatic impairment: No dosage adjustment typically needed
- Elderly: Consider reduced dosage due to potential renal impairment
- Pediatrics: Safety and effectiveness established for specific formulations in children 5+ years
- Swallow delayed-release tablets whole; do not crush or chew
- Take with or without food consistently
- Separate dosing from antacids by 2-3 hours
- Rectal formulations should be retained for several hours
Pharmacokinetics
Absorption: Minimal systemic absorption (10-30% of oral dose); primarily local action in colon Distribution: Low volume of distribution; poorly penetrates blood-brain barrier Metabolism: Extensive acetylation in gut wall and liver via N-acetyltransferase Elimination: Primarily excreted in feces as unchanged drug; renal excretion of metabolites Half-life: 5-10 hours for acetylated metaboliteContraindications
- Hypersensitivity to mesalamine, salicylates, or any component of formulation
- Severe renal impairment (CrCl <30 mL/min)
- History of salicylate sensitivity
- Patients with pyloric stenosis (for specific formulations)
Warnings and Precautions
Renal Toxicity: May cause nephrotoxicity including interstitial nephritis; monitor renal function at baseline and periodically during treatment Acute Intolerance Syndrome: May mimic ulcerative colitis flare with cramping, abdominal pain, bloody diarrhea Hypersensitivity Reactions: Rash, fever, myocarditis, pericarditis reported Hepatic Effects: Rare reports of hepatitis, liver function abnormalities Pulmonary Effects: Rare cases of interstitial lung disease Blood Dyscrasias: Monitor for signs of blood disordersDrug Interactions
- Anticoagulants: Potential increased risk of bleeding
- NSAIDs: May increase nephrotoxic potential
- Lactobacillus preparations: Theoretical interaction with pH-dependent formulations
- Probenecid: May decrease mesalamine excretion
- Thiopurines: Increased risk of blood dyscrasias when combined
Adverse Effects
Common (>1%):- Headache (15%)
- Abdominal pain (8%)
- Nausea (6%)
- Diarrhea (5%)
- Flatulence (4%)
- Rash (3%)
- Nephrotoxicity (interstitial nephritis)
- Pancreatitis
- Pericarditis
- Hepatitis
- Blood dyscrasias (agranulocytosis, aplastic anemia)
- Severe hypersensitivity reactions
Monitoring Parameters
- Renal function: Serum creatinine at baseline, then every 3-6 months
- Urinalysis: For proteinuria and cellular casts
- Liver function tests: Periodically
- Complete blood count: At baseline and as clinically indicated
- Disease activity: Symptom monitoring, endoscopic evaluation
- Therapeutic response: Improvement in bowel symptoms, inflammatory markers
Patient Education
- Take medication exactly as prescribed; do not alter dosage without medical advice
- Report any of the following immediately: fever, rash, unusual bleeding/bruising, dark urine, decreased urine output, severe abdominal pain
- Understand that improvement may take several weeks
- Keep all follow-up appointments for monitoring
- Inform all healthcare providers about mesalamine use
- Store medication properly according to specific formulation requirements
- Do not use during pregnancy without medical supervision (Category B)
- Breastfeeding is generally considered safe but discuss with healthcare provider
References
1. Kornbluth A, Sachar DB; Practice Parameters Committee of the American College of Gastroenterology. Ulcerative colitis practice guidelines in adults: American College of Gastroenterology, Practice Parameters Committee. Am J Gastroenterol. 2010;105(3):501-523. 2. Sandborn WJ, Hanauer SB. Systematic review: the pharmacokinetic profiles of oral mesalazine formulations and mucosal drug concentrations in inflammatory bowel disease. Aliment Pharmacol Ther. 2003;17(1):29-42. 3. Ford AC, Achkar JP, Khan KJ, et al. Efficacy of 5-aminosalicylates in ulcerative colitis: systematic review and meta-analysis. Am J Gastroenterol. 2011;106(4):601-616. 4. Lichtenstein GR, Kamm MA, Boddu P, et al. Effect of once- or twice-daily MMX mesalamine (SPD476) for the induction of remission of mild to moderately active ulcerative colitis. Clin Gastroenterol Hepatol. 2007;5(1):95-102. 5. Product Information: Lialda® (mesalamine) delayed-release tablets. Shire US Inc.; 2021. 6. Feagan BG, Macdonald JK. Oral 5-aminosalicylic acid for maintenance of remission in ulcerative colitis. Cochrane Database Syst Rev. 2012;10:CD000544.