Balsalazide Disodium

Pronunciation

Class: Anti-inflammatory Agents
VA Class: GA900
Chemical Name: 5-[[4-[[(2-carboxyethyl)amino]carbonyl]-phenyl]azo]-2-hydroxybenzoic acid disodium dihydrate
Molecular Formula: C17H13N3Na2O6•2H2O
CAS Number: 150399-21-6
Brands: Colazal

Introduction

Anti-inflammatory agent with GI tract activity; prodrug of mesalamine.1 2 3 9

Uses for Balsalazide Disodium

Ulcerative Colitis

Management of active, mild to moderate ulcerative colitis.1 2 3 4 7 8 9

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Crohn’s Disease

May be beneficial in the management of Crohn's disease involving the colon.10 11 12 13

Balsalazide Disodium Dosage and Administration

Administration

Oral Administration

Administer orally 3 times daily.1

Dosage

Available as balsalazide disodium; dosage expressed in terms of the salt.6

Daily dosage of 6.75 g is equivalent to mesalamine 2.4 g.1

Adults

Ulcerative Colitis
Oral

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

Crohn’s Disease
Oral

2–6 g daily may be used.12

Prescribing Limits

Adults

Safety and efficacy not established beyond 12 weeks.1

Cautions for Balsalazide Disodium

Contraindications

  • Known hypersensitivity to salicylates, balsalazide or its metabolites, or any ingredient in the formulation.1

Warnings/Precautions

Major Toxicities

GI Effects

Exacerbation of preexisting symptoms of ulcerative colitis has been reported rarely.1

General Precautions

Gastric Retention

Potential for prolonged gastric retention of basalazide capsules in patients with pyloric stenosis.1

Sodium Content

Each g of balsalazide disodium (as commercially available 750-mg capsules) provides approximately 5 mEq (115 mg) of sodium.1 14

Specific Populations

Pregnancy

Category B.1

Lactation

Not known whether balsalazide is distributed into milk.1 Caution if used in nursing women.1

Pediatric Use

Safety and efficacy not established in children <18 years of age.1 6

Geriatric Use

Insufficient experience in patients >65 years of age to determine whether geriatric patients respond differently than younger adults.6

Hepatic Impairment

Safety and efficacy not established in patients with hepatic impairment.1

Renal Impairment

Safety and efficacy not established in patients with renal impairment.1 Use with caution in patients with renal impairment or a history of renal disease, since renal toxicity has been reported in patients receiving other mesalamine preparations.1

Common Adverse Effects

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 fatigue.2

Interactions for Balsalazide Disodium

Specific Drugs

Drug

Interaction

Comments

Anti-infectives, oral

Potential for interference with bacterial metabolism and release of mesalamine in the colon1

Theoretical; no formal interaction studies to date1

Immunosuppressive agents (azathioprine, mercaptopurine)

Potential for interference with metabolism of immunosuppressive agents by thiopurine methyltransferase5 9

Balsalazide Disodium Pharmacokinetics

Absorption

Bioavailability

Absolute bioavailability undetermined in healthy individuals; absorption very limited and variable.1

Systemic exposure (based on mean AUC) in ulcerative colitis patients receiving 1.5 g twice daily for 1 year is up to 60 times greater than that in healthy individuals receiving the same dosage.1

Distribution

Plasma Protein Binding

>99%.1

Elimination

Metabolism

Azo-linkage is cleaved in the colon by intestinal flora to form mesalamine and 4-aminobenzoyl-β-alanine.1 2 3 9

Elimination Route

In healthy individuals, excreted principally in feces as metabolites (65%) and unchanged drug (<1%); also excreted in urine as N-acetylated metabolites (up to 25%) and unchanged drug (<1%).1 6

In ulcerative colitis patients in remission after 1 year of balsalazide therapy, excreted in urine as N-acetylated metabolites (20–25%), mesalamine (<4%), and unchanged drug (<1%); fecal elimination not studied.1

Stability

Storage

Oral

Capsules

25°C (may be exposed to 15–30°C).1

Actions

  • Prodrug with little or no pharmacologic activity until cleaved to form mesalamine (active moiety) and 4-aminobenzoyl-β-alanine.1 2 3 9

  • Exerts local (not systemic) anti-inflammatory effects in the GI tract.1 6 9

  • May reduce inflammation in the colon by inhibiting cyclooxygenase and lipoxygenase, which catalyze the formation of prostaglandin precursors (endoperoxides) and of leukotrienes and hydroxyeicosatetraenoic acids, respectively, from arachidonic acid and/or its metabolites.1 2 6

Advice to Patients

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 6

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.1

  • Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Balsalazide Disodium

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules

750 mg

Colazal

Salix

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Balsalazide Disodium 750MG Capsules (MYLAN): 280/$319.98 or 840/$945.97

Colazal 750MG Capsules (SALIX PHARMACEUTICALS): 280/$449.96 or 560/$865.92

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions May 1, 2006. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

1. Salix Pharmaceuticals. Colazal (balsalazide disodium) capsules prescribing information. Raleigh, NC; 2003 Aug.

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. [IDIS 399117] [PubMed 9428213]

4. Gross V. Efficacy of different mesalamine-releasing drugs. Gastroenterology. 1998; 115:1306-7. [IDIS 418378] [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. [IDIS 430613] [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.

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. [IDIS 484721] [PubMed 12167685]

12. Hanauer SB. Inflammatory bowel disease. N Engl J Med. 1996; 334:841-8. [IDIS 361805] [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.

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