Pharmacology Update
Balsalazide Disodium Capsules (Colazal—Salix Pharmaceuticals)
By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD
The fda has approved balsalazide disodium for the treatment of ulcerative colitis, the first new drug approved for this indication in more than 10 years. Balsalazide is the prodrug of mesalamine in which the sulfapyridine moiety of sulfasalazine is replaced with aminobenzoyl-beta-alanine. It will be marketed by Salix Pharmaceuticals as Colazal.
Indications
Balsalazide is indicated for the treatment of mildly to moderately active ulcerative colitis.
Dosage
The usual dose is three 750 mg capsules taken three times a day for eight weeks. Some patients may require treatment up to 12 weeks.1
Balsalazide will be supplied as 750 mg capsules.
Potential Advantages
A report suggests that balsalazide is more effective and better tolerated than delayed-release mesalamine (Asacol).2 In this study, more patients had symptomatic remission (78% vs 45%; P = 0.012) and complete remission (54% vs 22%; P = 0.0018) as assessed by sigmoidocopy at eight weeks with balsalazide vs. mesalamine. In addition, fewer patients reported adverse events (48% vs 71%; P = 0.024). Balsalazide also had a more rapid action with the median time to the first completely symptom-free day of 10 vs. 25 days (P = 0.0039). Patients with more severe disease who were treated with balsalazide had a higher probability of achieving complete remission than patients with milder disease treated with mesalamine.
Potential Disadvantages
Balsalazide requires three times a day dosing. The most common adverse event is abdominal pain (11%).3 Balsalazide has not been FDA approved for the maintenance of ulcerative colitis.
Comments
Balsalazide is a prodrug of mesalamine where the sulfapyridine of sulfasalazine is replaced with an inert carrier, 4-aminobenzoyl-beta alanine. After oral administration, mesalamine is released by cleavage by colonic bacterial azoreductase. In a randomized, double-blind study (n = 99) balsalazide (6.75 g/d) was found to be more effective and better tolerated in the treatment of ulcerative colitis than a delayed-release mesalazine (Asacol; 2.4 g/d). Balsalazide has not been approved by the FDA for the maintenance of ulcerative colitis, although data suggest that it may be comparable to mesalazine over a 12-month study period for this indication.4
Clinical Implications
Ulcerative colitis is an inflammatory disease of the colon and rectum with an estimated annual incidence of 2-6 per 100,000 in the United States.5 The disease is believed to be caused by a genetically based regulatory disturbance of the intestinal mucosa or systemic immune response. Pharmacotherapy includes anti-inflammatory drugs such as 5-aminosalicylate (mesalamine) and corticosteroids and immune-modulating agents such as azathioprine and 6-mercaptopurine. Mesalamine is generally used for mild-to-moderately active disease and for maintaining remission. Sulfasalazine, the oldest mesalamine prodrug, is limited by its side effects, most of which are attributed to sulfapyridine. Several delivery systems of mesalamine have been developed which include two pH-dependent controlled-released formulations (Asacol, Pentasa) and olsalazine which is a linked pair of mesalamine molecules requiring colonic bacterial cleavage. The objective of all these agents is to deliver mesalamine to the colon while reducing systemic absorption.
Sulfasalazine is limited by various side effects, olsalazine causes diarrhea, and controlled-release formulations have shown systemic absorption.6
Balsalazide may prove to be a well tolerated and more colon specific delivery system for mesalamine. Balsalazide is expected to be launched in January 2001.
References
1. Colazal Product Information. Salix Pharmaceuticals, July 2000.
2. Green JR, et al. Gastroenterology 1998;114:15-22.
3. Prakash A, CM Spencer. Drugs 1998;56(1):83-86.
4. Green JRB, et al. Aliment Pharmacol Ther 1998;12: 1207-1216.
5. Kornbluth A, Sachat DB. Am J Gastroenterol 1997; 92(2):204-211.
6. Christensen LA. Dan Med Bull 2000;47(1):20.
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