Balsalazide is used in the management of mildly to moderately active ulcerative colitis.1, 2, 3, 4, 7, 8, 9 Safety and efficacy of balsalazide therapy have not been established beyond 12 weeks.1
Safety and efficacy of balsalazide have been evaluated in 2 randomized, double-blind studies of 8 weeks' duration in patients with mildly to moderately active ulcerative colitis with sigmoidoscopic findings of friable or spontaneously bleeding mucosa.1, 2, 4, 6, 7, 8 In these studies, improvements in rectal bleeding,6 stool frequency, or sigmoidoscopic findings were reported in 55-65, 49-59, or 74-79% of patients, respectively, who received balsalazide 6.75 g daily for 8 weeks.1, 8 Balsalazide also reduced abdominal pain and improved functional assessment scores.1, 8
Results of clinical studies indicate that balsalazide 6.75 g daily appears to be at least as effective as sulfasalazine 3 g daily or mesalamine 2.4 g daily in improving symptoms in patients with ulcerative colitis who received the drugs orally for up to 12 weeks.2, 3, 9 In one randomized, double-blind study, symptomatic improvement or complete remission (defined as asymptomatic or with mild symptoms, sigmoidoscopy grade 0 or 1, and no rectal steroid use within 4 days) was achieved in 88 or 62%, respectively, of patients receiving balsalazide 6.75 mg daily and in 57 or 37%, respectively, of those who received mesalamine 2.4 g daily for 12 weeks.2, 3, 9 Treatment with balsalazide appears to be associated with more rapid symptomatic improvement (12-14 days earlier) compared to that with mesalamine.2, 3, 7 However, some clinicians state that a relative therapeutic advantage of balsalazide over mesalamine remains to be established.9
Although controlled studies assessing the efficacy of balsalazide are lacking, limited data indicate that use of the drug may be beneficial in the management of Crohn's disease† involving the colon.10, 11, 12, 13
Balsalazide disodium is administered orally 3 times daily.1
Dosage of balsalazide disodium is expressed in terms of balsalazide.6 The recommended adult dosage of balsalazide is 6.75 g (equivalent to 2.4 g of mesalamine) daily administered as 3 equally divided doses of 2.25 g (three 750-mg capsules 3 times daily) for 8 weeks;1, 9 some patients may require up to 12 weeks of therapy.1 The total daily dosage of balsalazide (6.75 g) is equivalent to approximately 2.4 g of mesalamine.1, 2, 6
For the management of Crohn's disease† (involving the colon), a balsalazide dosage of 2-6 g daily may be used.12
No special population dosage recommendations at this time.6
Known hypersensitivity to salicylates, balsalazide, or its metabolites, or any ingredient in the formulation.1
Exacerbation of preexisting symptoms of ulcerative colitis has been reported rarely.1
Potential for prolonged gastric retention of the drug in patients with pyloric stenosis.1
Category B. (See Users Guide.)
It is not known whether balsalazide is distributed in human milk.1 Because many drugs are excreted in human milk, caution is advised if the drug is administered in nursing women.1
Safety and efficacy not established in children younger than 18 years of age.6
Experience in those 65 years of age and older insufficient to determine whether they respond differently from younger adults.6
Safety and efficacy not established in patients with hepatic impairment.1
Safety and efficacy not established in patients with renal impairment.1 However, since renal toxicity has been reported in patients receiving other preparations of mesalamine, the manufacturer recommends that balsalazide be used with caution in patients with renal impairment or a history of renal disease.1
Adverse effects occurring in 4% or more of patients receiving balsalazide include headache,1, 2, 3, 9 abdominal pain,1, 2, 3, 9 diarrhea,1, 2, 9 nausea,1, 2, 3, 9 vomiting,1, 3 respiratory infection,1 arthralgia,1 flatulence,2 and fatigue.2
Some adverse effects (e.g., abdominal pain, fatigue, nausea) appear to occur more frequently in women.1 The manufacturer states that certain adverse effects (e.g., abdominal pain, rectal bleeding, anemia) may be manifestations of ulcerative colitis.1, 6
No formal drug interaction studies have been performed.1
Potential pharmacologic interaction (e.g., interference with release of mesalamine in the colon).1
Azathioprine and 6-Mercaptopurine
Potential pharmacokinetic interaction (balsalazide may interfere with metabolism of these drugs by inhibition of thiopurine methyltransferase, an enzyme involved in the metabolism of the immunosuppressants).5, 9
Balsalazide is a GI anti-inflammatory agent.1, 2, 3 Balsalazide is a prodrug of mesalamine (5-aminosalicylic acid) and has little or no pharmacologic activity until enzymatically cleaved in the colon to provide mesalamine and the inert 4-aminobenzoyl-β-alanine.1, 2, 3, 9 Thus, the spectrum of pharmacologic activity of balsalazide generally is similar to that of mesalamine.6
Mesalamine exhibits anti-inflammatory activity in the GI tract.1, 2 Although the exact mechanism of action of mesalamine has not been fully elucidated, the drug appears to exert its anti-inflammatory effects locally, in the GI tract, rather than systemically.1, 6, 9 Limited data indicate that mesalamine may reduce inflammation in the colon by inhibiting cyclooxygenase, an enzyme that catalyzes the formation of prostaglandin precursors (endoperoxides) from arachidonic acid.1, 6 Mesalamine also inhibits leukotriene synthesis, possibly by inhibiting lipoxygenase, an enzyme that catalyzes the formation of leukotrienes and hydroxyeicosatetraenoic acids (HETEs) from arachidonic acid and its metabolites.1, 2 Although the role of arachidonic acid metabolites in the pathogenesis of inflammatory bowel disease remains to be determined, mucosal production of these metabolites, both through the cyclooxygenase and the lipoxygenase pathways, appears to be increased in patients with inflammatory bowel disease.1
Following oral administration, balsalazide disodium passes intact into the colon where the azo-linkage is cleaved by intestinal flora to form mesalamine and 4-aminobenzoyl-β-alanine.1, 2, 3, 9 A small portion of mesalamine is absorbed and undergoes N 4-acetylation.1, 2, 6 Balsalazide and/or its metabolites are excreted principally in feces.1 Approximately 65% of an administered dose is excreted in feces as mesalamine, 4-aminobenzoyl-β-alanine, or N -acetylated metabolites, and up to 25% is excreted in urine as N -acetylated metabolites;1, 6 less than 1% of the dose is excreted in urine or feces as unchanged drug.6 (For further information on chemistry, pharmacology, and pharmacokinetics of mesalamine, see Mesalamine 56:36.)
Each g of balsalazide disodium (as commercially available 750-mg capsules) provides approximately 5 mEq (115 mg) of sodium.1, 14
Importance of women informing clinicians if they are or plan to become pregnant or to breast-feed.1, 6
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.1
Additional Information
Overview (see Users Guide). For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
1. Salix Pharmaceuticals. Colazal® (balsalazide disodium) capsules prescribing information. Raleigh, NC; 2003Aug.
2. Prakash A, Spencer CM. Balsalazide. Drugs . 1998; 56:83-9. [PubMed 9664201]
3. Green JRB, Lobo AJ, Holdsworth CD et al. Balsalazide is more effective and better tolerated than mesalamine in the treatment of acute ulcerative colitis. Gastroenterology . 1998; 114:15-22. [PubMed 9428213]
4. Gross V. Efficacy of different mesalamine-releasing drugs. Gastroenterology . 1998; 115:1306-7. [PubMed 9797396]
5. Lowry PW, Szumlanski CL, Weinshilboum RM et al. Balsalazide and azathioprine or 6-mercaptopurine: evidence for a potentially serious drug interaction. Gastroenterology . 1999; 116:1505-6. [PubMed 10391741]
6. Novartis, East Hanover, NJ: Personal communication.
7. Pruitt R, Hanson J, Safdi M et al. Balsalazide is superior to mesalamine in the time to improvement of signs and symptoms of acute ulcerative colitis. Gastroenterology . 2000; 118(Suppl 2 Part 1): A120-1.
8. Levine DS, Pruitt R, Riff D et al. A multi-center double-blind dose-response trial of Colazide® (balsalazide disodium) and Asacol® (mesalamine) for mild-moderately active ulcerative colitis. Gastroenterology . 1997; 112(Suppl):A1026. [PubMedCentral]
9. Anon. Oral balsalazide (Colazal®) for ulcerative colitis. Med Lett Drugs Ther . 2001; 43:62-3. [PubMed 11468602]
10. Biancone L, Tosti V, Fina D et al. Review article: maintenance treatment of Crohn's disease. Aliment Pharmacol Ther . 2003; 17(Suppl. 2):31-37. [PubMed 12786610]
11. Podolsky DK. Inflammatory Bowel Disease. N Engl J Med . 2002; 347:417-29. [PubMed 12167685]
12. Hanauer SB. Inflammatory bowel disease. N Engl J Med . 1996; 334:841-8. [PubMed 8596552]
13. Pardi DS, Loftus EV Jr, Camilleri M. Treatment of inflammatory bowel disease in the elderly: an update. Drugs Aging . 2002; 19:355-63. [PubMed 12093322]
14. Salix Pharmaceuticals. Raleigh, NC: Personal communication.