Balsalazide

357.32

357.32

1312995-182-4

P80AL8J7ZP

DTXSID7040653

A - Alimentary tract and metabolism

148.65000

1.00

yellow to orange crystalline powder

1.4±0.1 g/cm3

254-255°C

1.650

Freely soluble as disodium salt

-20°C Freezer

R20/21/22

S36/37

A single oral dose of balsalazide disodium at 5 grams/kg or 4-aminobenzoyl-(beta)-alanine, a metabolite of balsalazide disodium, at 1 gram/kg was non-lethal in mice and rats. No symptoms of acute toxicity were seen at these doses.

In large registration trials of various forms of mesalamine, serum enzyme elevations were no more common with the products than with placebo therapy and were less common than with sulfasalazine. In these large studies, there were no reported instances of clinically apparent liver injury. Since approval and wide scale usage, however, there have been isolated reports of acute and chronic liver injury with jaundice attributed to mesalamine therapy. Clinically apparent liver injury is estimated to occur at an incidence of 3.2 cases per million prescriptions. Several patterns of injury have been reported, including asymptomatic and mild elevations in serum ALT levels, mild hepatitis accompanying a hypersensitivity reaction within a few days or weeks of starting (sometimes following a similar reaction to sulfasalazine), drug fever with accompanying serum enzyme elevations or mild hepatitis, and more typically, idiosyncratic cholestatic or hepatocellular liver injury (Cases 1 and 2), which typically arises after 1 to 6 months of treatment and is not accompanied by signs of hypersensitivity (rash, fever, eosinophilia). Most cases of liver injury with jaundice have been mild-to-moderate in severity and resolve rapidly upon stopping. In cases with hypersensitivity reactions, corticosteroid therapy is often used and appears to speed recovery. There have been no convincing reports of fatal acute liver injury, chronic hepatitis or vanishing bile duct syndrome attributable to mesalamine.

≥99%

For the treatment of mildly to moderately active ulcerative colitis.|FDA Label

Mesalamine, also known as mesalazine and 5-aminosalicylate, is an orally available, antiinflammatory agent used for the treatment of ulcerative colitis to both induce and maintain remissions in disease. Mesalamine therapy has been associated with a low rate of serum enzyme elevations during therapy and with rare instances of clinically apparent acute liver injury.

Gastrointestinal Agents

Balsalazide is a prodrug that has little or no pharmacologic activity until it is enzymatically cleaved in the colon to produce mesalamine (5-aminosalicylic acid), an anti inflammatory drug indicated for the treatment of mildly to moderately active ulcerative colitis. Balsalazide disodium is delivered intact to the colon where it is cleaved by bacterial azoreduction to release equimolar quantities of mesalamine, which is the therapeutically active portion of the molecule, and the intert 4-aminobenzoyl-(beta)-alanine. As a result, the spectrum of pharmacologic activity of balsalazide is similar to that of mesalamine.

Anti-inflammatory agents that are non-steroidal in nature. In addition to anti-inflammatory actions, they have analgesic, antipyretic, and platelet-inhibitory actions.They act by blocking the synthesis of prostaglandins by inhibiting cyclooxygenase, which converts arachidonic acid to cyclic endoperoxides, precursors of prostaglandins. Inhibition of prostaglandin synthesis accounts for their analgesic, antipyretic, and platelet-inhibitory actions; other mechanisms may contribute to their anti-inflammatory effects. (See all compounds classified as Anti-Inflammatory Agents, Non-Steroidal.)|Drugs used for their effects on the gastrointestinal system, as to control gastric acidity, regulate gastrointestinal motility and water flow, and improve digestion. (See all compounds classified as Gastrointestinal Agents.)

Low and variable, intact balsalazide is poorly absorbed systemically.|The products of the azoreduction of this compound, 5-ASA and 4-aminobenzoyl-ß-alanine, and their N-acetylated metabolites have been identified in plasma, urine and feces. Following single-dose administration of 2.25 g COLAZAL (three 750 mg capsules) under fasting conditions in healthy subjects, mean urinary recovery of balsalazide, 5-ASA, and N-Ac-5-ASA was 0.20%, 0.22% and 10.2%, respectively.

Cleaved in the colon via bacterial azoreduction to 5–aminosalicylic acid (5–ASA) and 4–aminobenzoyl-beta-alanine, the inactive carrier moiety.

Half-life could not be determined.

The mechanism of action of 5-aminosalicylic acid is unknown, but appears exert its anti-inflammatory effects locally (in the GI tract) rather than systemically. Mucosal production of arachidonic acid metabolites, both through the cyclooxygenase pathways (catalyzes the formation of prostaglandin precursors from arachidonic acid), and through the lipoxygenase pathways (catalyzes the formation of leukotrienes and hydroxyeicosatetraenoic acids from arachidonic acid and its metabolites), is increased in patients with chronic inflammatory bowel disease. Therefore, it is possible that 5-aminosalicylic acid diminishes inflammation by blocking production of arachidonic acid metabolites in the colon through both the inhibition of cyclooxygenase and lipoxygenase.

5-(carboxyethylcarbamoyl-4-phenylazo)salicylic acid

Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients