Introduction
Balsalazide disodium is a prodrug mesalamine (5-aminosalicylic acid) formulation used in the management of inflammatory bowel disease. It represents an important therapeutic option in the treatment of ulcerative colitis, designed to deliver the active anti-inflammatory component specifically to the colon while minimizing systemic exposure and adverse effects.
Mechanism of Action
Balsalazide is a prodrug that undergoes enzymatic cleavage by colonic bacterial azoreductases to release mesalamine (5-aminosalicylic acid or 5-ASA), the active therapeutic moiety. Mesalamine acts locally in the colonic mucosa through multiple anti-inflammatory mechanisms:
- Inhibition of cyclooxygenase and lipoxygenase pathways
- Scavenging of reactive oxygen species
- Inhibition of cytokine production (particularly IL-1 and TNF-α)
- Interference with neutrophil chemotaxis and activation
- Reduction of nuclear factor kappa B (NF-κB) activation
The 4-aminobenzoyl-β-alanine carrier molecule ensures targeted delivery to the colon, with less than 1% of the prodrug absorbed systemically.
Indications
FDA-approved indications:- Treatment of mildly to moderately active ulcerative colitis in patients 5 years and older
- Maintenance of remission of ulcerative colitis in adults
- Crohn's colitis (limited evidence)
- Pouchitis (limited evidence)
Dosage and Administration
Adults:- Active disease: 2.25 g three times daily (6.75 g total daily dose) for 8-12 weeks
- Maintenance therapy: 1.5 g twice daily (3 g total daily dose) or 2.25 g three times daily (6.75 g total daily dose)
- Active disease:
- 6.75 g/day for patients 5 to <17 years weighing ≥55 kg - 2.25-6.75 g/day based on weight for patients 5 to <17 years weighing <55 kg
Administration:- Administer whole capsules with water; do not crush or chew
- May be taken with or without food
- Maintain adequate hydration during therapy
- Renal impairment: Use with caution; monitor renal function
- Hepatic impairment: No dosage adjustment recommended
- Elderly: Use with caution due to potential age-related renal impairment
Pharmacokinetics
Absorption: Minimal systemic absorption of intact prodrug (<1%) Distribution: Primarily local to gastrointestinal tract Metabolism: Cleaved by colonic bacterial azoreductases to release mesalamine and 4-aminobenzoyl-β-alanine Elimination:- Mesalamine: Primarily excreted in feces; renal excretion of acetylated metabolite
- 4-aminobenzoyl-β-alanine: Absorbed and excreted renally
Contraindications
- Hypersensitivity to salicylates, mesalamine, or any component of the formulation
- Patients with history of hypersensitivity to sulfasalazine
Warnings and Precautions
Boxed Warning:- Renal impairment: May cause renal toxicity; monitor renal function before and during therapy
- Mesalamine-induced acute intolerance syndrome (fever, cramping, acute abdominal pain, bloody diarrhea)
- Hypersensitivity reactions (myocarditis, pericarditis, pneumonitis)
- Hepatic failure (rare)
- Exacerbation of ulcerative colitis symptoms
- Photosensitivity
- Blood dyscrasias (agranulocytosis, aplastic anemia)
- Use caution in patients with pyloric stenosis or structural gastrointestinal obstruction
Drug Interactions
Significant interactions:- Nephrotoxic drugs (NSAIDs, aminoglycosides, cyclosporine): Increased risk of renal toxicity
- Azathioprine/6-mercaptopurine: Potential increased risk of blood dyscrasias
- Anticoagulants: Theoretical increased risk of bleeding
- Probiotics: May affect bacterial metabolism of prodrug
Adverse Effects
Common (≥5%):- Headache (15%)
- Abdominal pain (12%)
- Nausea (11%)
- Diarrhea (9%)
- Upper respiratory infection (7%)
- Arthralgia (7%)
- Rhinitis (6%)
- Renal impairment (0.3%)
- Pancreatitis (<0.1%)
- Hepatic failure (<0.1%)
- Pericarditis (<0.1%)
- Blood dyscrasias (<0.1%)
- Severe cutaneous reactions (Stevens-Johnson syndrome)
Monitoring Parameters
Baseline:- Complete blood count with differential
- Renal function tests (BUN, serum creatinine)
- Liver function tests
- Urinalysis
- Renal function every 3-6 months during first year, then annually
- CBC periodically
- Liver function tests as clinically indicated
- Monitor for signs of acute intolerance syndrome
- Assess therapeutic response and disease activity
- Annual renal function assessment
- Periodic monitoring for pulmonary and cardiac symptoms
Patient Education
- Take medication exactly as prescribed; do not crush or chew capsules
- Report any of the following immediately:
- Unexplained fever, sore throat, or bruising - Chest pain or shortness of breath - Severe abdominal pain, cramping, or bloody diarrhea - Rash or skin reactions - Decreased urine output
- Maintain adequate fluid intake
- Regular follow-up appointments are essential
- Inform all healthcare providers about balsalazide use
- Protect from light and moisture; store at room temperature
- Do not discontinue medication without consulting your physician
References
1. Sandborn WJ, Hanauer SB. Systematic review: the pharmacokinetic profiles of oral mesalazine formulations and mesalazine pro-drugs used in the management of ulcerative colitis. Aliment Pharmacol Ther. 2003;17(1):29-42. 2. Pruitt R, Hanson J, Safdi M, et al. Balsalazide is superior to mesalamine in the time to improvement of signs and symptoms of acute mild-to-moderate ulcerative colitis. Am J Gastroenterol. 2002;97(6):1398-1407. 3. Green JR, Lobo AJ, Holdsworth CD, et al. Balsalazide is more effective and better tolerated than mesalamine in the treatment of acute ulcerative colitis. Gastroenterology. 1998;114(1):15-22. 4. Package Insert. Balsalazide disodium. Revised 2022. 5. Kornbluth A, Sachar DB; Practice Parameters Committee of the American College of Gastroenterology. Ulcerative colitis practice guidelines in adults: update 2010. Am J Gastroenterol. 2010;105(3):501-523. 6. 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. 7. Feagan BG, Macdonald JK. Oral 5-aminosalicylic acid for maintenance of remission in ulcerative colitis. Cochrane Database Syst Rev. 2012;10:CD000544.