Active ingredient: Mesalamine - Basic Profile / Key Facts

Basic Profile / Key Facts

Drug Category

• Anti-Inflammatory Agents, Non-Steroidal

Dosage Forms

• Rectal suppository (500 mg or 1000 mg)

Indications

For the treatment of active ulcerative proctitis.

Pharmacology

Sulfasalazine has been used in the treatment of ulcerative colitis for over 55 years. It is split by bacterial action in the colon into sulfapyridine (SP) and mesalamine (5-ASA). It is thought that the mesalamine component only is therapeutically active in ulcerative colitis.

Mechanism of Action

Although the mechanism of action of mesalamine (and sulfasalazine) is not fully understood, it appears to be topical rather than systemic. Mucosal production of arachidonic acid metabolites, both through the cyclooxygenase pathways, i.e., prostanoids, and through the lipoxygenase pathways, i.e., leukotrienes and hydroxyeicosatetraenoic acids, is increased in patients with chronic inflammatory bowel disease, and it is possible that mesalamine diminishes inflammation by blocking cyclooxygenase and inhibiting prostaglandin production in the colon.

Absorption

20 to 30% absorbed following oral administration. 10 to 35% absorbed from the colon (rectal suppository) - extent of absorption is determined by the length of time the drug is retained in the colon.

Toxicity

Oral, mouse: LD₅₀ = 3370 mg/kg; Oral, rat: LD₅₀ = 2800 mg/kg; Skin, rabbit: LD₅₀ = >5 gm/kg. There have been no documented reports of serious toxicity in man resulting from massive overdosing with mesalamine. Under ordinary circumstances, mesalamine absorption from the colon is limited.

Biotrnasformation / Drug Metabolism

Rapidly and extensively metabolized, mainly to N-acetyl-5-ASA (Ac-5-ASA) in the intestinal mucosal wall and the liver. Ac-5-ASA is further acetylated (deactivated) in at least 2 sites, the colonic epithelium and the liver.

Contraindications

CANASA® 500 mg and 1000 mg Suppositories are contraindicated in patients who have demonstrated hypersensitivity to mesalamine (5-aminosalicylic acid) or to the suppository vehicle [saturated vegetable fatty acid esters (Hard Fat, NF)], or to salicylates (including aspirin).

Drug Interactions

No information provided.