Introduction
Colazal (balsalazide disodium) is an oral prodrug mesalamine (5-aminosalicylic acid) formulation specifically designed for the treatment of inflammatory bowel disease. As a colon-specific anti-inflammatory agent, it delivers the active therapeutic component directly to the site of inflammation in the colon while minimizing systemic exposure.
Mechanism of Action
Balsalazide disodium is a prodrug that remains intact until it reaches the colon, where bacterial azoreductases cleave the compound to release mesalamine (5-aminosalicylic acid). Mesalamine acts locally in the colonic mucosa to exert anti-inflammatory effects through multiple mechanisms:
- Inhibition of cyclooxygenase and lipoxygenase pathways
- Scavenging of reactive oxygen species
- Inhibition of cytokine production (IL-1, TNF-α)
- Interference with neutrophil chemotaxis and function
- Reduction of nuclear factor kappa B (NF-κB) activation
Indications
- Treatment of mildly to moderately active ulcerative colitis in patients 5 years and older
- Maintenance of remission in ulcerative colitis
Dosage and Administration
Adults:- Active ulcerative colitis: 2.25 g three times daily for 8 weeks
- Maintenance therapy: 2.25 g twice daily or 1.5 g three times daily
- Either 2.25 g or 6.75 g once daily for 8 weeks
- Dosing based on body weight: 50-70 kg: 2.25 g daily; >70 kg: 6.75 g daily
- Administer with or without food
- Swallow capsules whole; do not crush or chew
- For patients who cannot swallow capsules, contents may be sprinkled on applesauce
- Renal impairment: Use with caution; monitor renal function
- Hepatic impairment: No specific dosage adjustment recommended
- Elderly: Consider potential decreased renal function
Pharmacokinetics
Absorption: Minimal systemic absorption; primarily delivered to colon Distribution: Localized to colonic mucosa; minimal systemic distribution Metabolism: Cleaved by colonic bacterial azoreductases to release mesalamine and 4-aminobenzoyl-β-alanine Elimination: Primarily excreted in feces as mesalamine and metabolites; minimal renal excretion Half-life: Approximately 1 hour for balsalazide; mesalamine half-life is 5-10 hoursContraindications
- Hypersensitivity to salicylates, balsalazide, or any component of the formulation
- Patients with history of hypersensitivity to mesalamine or sulfasalazine
Warnings and Precautions
- Renal impairment: Monitor renal function at baseline and during therapy
- Mesalamine-induced acute intolerance syndrome: May present with cramping, acute abdominal pain, bloody diarrhea, fever, headache, and rash
- Hepatic effects: Rare reports of hepatotoxicity; monitor liver enzymes
- Pulmonary effects: Interstitial lung disease reported with mesalamine derivatives
- Blood dyscrasias: Rare reports of agranulocytosis, aplastic anemia
- Pregnancy: Category B - Use only if clearly needed
- Lactation: Mesalamine excreted in breast milk; use with caution
Drug Interactions
- Anticoagulants: Potential increased risk of bleeding
- Nonsteroidal anti-inflammatory drugs: May increase risk of nephrotoxicity
- Azathioprine/6-mercaptopurine: Potential additive myelosuppression
- Probenecid: May decrease renal excretion of mesalamine metabolites
- Thiopurine methyltransferase inhibitors: Potential additive effects
Adverse Effects
Common (≥5%):- Headache (15%)
- Abdominal pain (12%)
- Diarrhea (10%)
- Nausea (9%)
- vomiting (6%)
- Respiratory infection (10%)
- Arthralgia (7%)
- Renal impairment (0.3%)
- Pancreatitis (<0.1%)
- Pericarditis (<0.1%)
- Hepatic failure (<0.1%)
- Blood dyscrasias (<0.1%)
- Severe cutaneous adverse reactions
Monitoring Parameters
- Baseline: Complete blood count, renal function (BUN, creatinine), liver function tests
- During therapy: Renal function every 3-6 months, liver enzymes periodically
- Symptom monitoring: Abdominal pain, diarrhea pattern, rectal bleeding
- Therapeutic response: Improvement in ulcerative colitis symptoms
- Adverse effects: Monitor for signs of intolerance syndrome
Patient Education
- Take medication exactly as prescribed; do not stop abruptly
- Swallow capsules whole; do not crush or chew
- Report any of the following immediately:
- Worsening abdominal pain - Bloody diarrhea - Fever, rash, or headache - Unusual bleeding or bruising - Yellowing of skin or eyes - Difficulty breathing
- Inform all healthcare providers about Colazal use
- Keep all follow-up appointments for monitoring
- Store at room temperature away from moisture
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. 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. 3. Colazal [package insert]. San Diego, CA: Salix Pharmaceuticals; 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, 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.