Introduction
Lialda (mesalamine) is an oral aminosalicylate anti-inflammatory medication used primarily for the treatment of ulcerative colitis. It is designed to deliver mesalamine directly to the colon, where it exerts its therapeutic effects with minimal systemic absorption.
Mechanism of Action
Mesalamine, the active component of Lialda, acts locally in the colon through several anti-inflammatory mechanisms. It inhibits cyclooxygenase and lipoxygenase pathways, reducing prostaglandin and leukotriene production. Mesalamine also scavenges reactive oxygen species, inhibits neutrophil chemotaxis and degranulation, and decreases cytokine production (particularly IL-1 and TNF-α). The multi-matrix (MMX) delivery system ensures targeted release throughout the colon.
Indications
- Treatment of mildly to moderately active ulcerative colitis in adults
- Maintenance of remission of ulcerative colitis in adults
Dosage and Administration
Active Ulcerative Colitis: 2.4-4.8 g orally once daily with meal for 8 weeks Maintenance Therapy: 2.4 g orally once daily with meal Special Populations:- Renal impairment: Use with caution; monitor renal function
- Hepatic impairment: No specific dosage adjustment recommended
- Elderly: Consider reduced dosage due to potential decreased renal function
- Pediatrics: Safety and effectiveness not established
Pharmacokinetics
Absorption: Minimal systemic absorption (<20%); primarily local action in colon Distribution: Low volume of distribution; poorly penetrates tissues Metabolism: Primarily metabolized via N-acetylation in colonic mucosa and liver Elimination: Half-life approximately 7 hours; excreted mainly in feces as unchanged drug and metabolites; renal excretion of absorbed portionContraindications
- Hypersensitivity to mesalamine, salicylates, or any component of formulation
- Patients with history of hypersensitivity to sulfasalazine
Warnings and Precautions
- Renal impairment: May cause interstitial nephritis; monitor renal function at baseline and periodically during treatment
- Mesalamine-induced acute intolerance syndrome: Symptoms may include cramping, acute abdominal pain, bloody diarrhea, and sometimes fever, headache, and rash
- Hepatic effects: Rare reports of hepatitis, liver function abnormalities
- Pulmonary effects: Rare reports of pulmonary fibrosis, interstitial pneumonitis
- Skin reactions: Severe cutaneous adverse reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis
- Pericarditis: Rare reports, usually in patients with history of pericarditis
Drug Interactions
- Warfarin: May enhance anticoagulant effect; monitor INR closely
- Azathioprine/6-mercaptopurine: Potential increased risk of blood dyscrasias
- Nonsteroidal anti-inflammatory drugs: May increase risk of renal adverse effects
- Probenecid: May decrease renal elimination of mesalamine metabolites
Adverse Effects
Common (>5%):- Headache (8%)
- Flatulence (6%)
- Abdominal pain (5%)
- Nausea, vomiting, diarrhea
- Dyspepsia, constipation
- Rash, pruritus
- Fatigue, fever
- Acute renal failure
- Pancreatitis
- Pericarditis
- Hepatitis
- Blood dyscrasias
- Severe cutaneous reactions
- Pulmonary fibrosis
Monitoring Parameters
- Baseline: Complete blood count, renal function tests (BUN, creatinine), liver function tests
- During therapy: Renal function every 3-6 months, liver function periodically
- Symptoms monitoring: Abdominal pain, bloody diarrhea, fever, rash
- Therapeutic response: Reduction in ulcerative colitis symptoms, endoscopic improvement
Patient Education
- Take with food to enhance delivery to colon
- Swallow tablets whole; do not crush or chew
- Report any of the following immediately: fever, rash, difficulty breathing, chest pain, unusual bleeding or bruising, severe abdominal pain, or bloody diarrhea
- Maintain adequate hydration
- Regular follow-up with healthcare provider for monitoring
- Inform all healthcare providers of Lialda use before any new medications
- Report any symptoms of kidney problems (decreased urine output, swelling, fatigue)
References
1. Sandborn WJ, et al. Once-daily mesalamine formulation for maintenance of remission in ulcerative colitis: randomized clinical trial. Am J Gastroenterol. 2009;104(2):363-373. 2. Lichtenstein GR, et al. Mesalamine capsules for the treatment of active ulcerative colitis: results of a controlled trial. Am J Gastroenterol. 2007;102(4):845-851. 3. Lialda [package insert]. Lexington, MA: Shire Pharmaceuticals Inc.; 2021. 4. Kornbluth A, Sachar DB. Ulcerative colitis practice guidelines in adults: American College of Gastroenterology, Practice Parameters Committee. Am J Gastroenterol. 2010;105(3):501-523. 5. Ford AC, et al. Efficacy of 5-aminosalicylates in ulcerative colitis: systematic review and meta-analysis. Am J Gastroenterol. 2011;106(4):601-616.