Mesalamine is useful in the induction or maintenance of remission in ulcerative colitis. It is usually used in mildly to moderately active ulcerative colitis.[1] For off-label use, clinicians may use mesalamine in Crohn disease after surgical resection of the affected bowel.[2][3][4]

The first-line treatment for mild to moderate ulcerative colitis is topical mesalamine.[5] For disease localized to the rectum, a suppository formulation is an option, but for the disease that extends into the sigmoid colon, mesalamine enemas are preferable. Overall, topical mesalamine formulations are preferred over oral forms and topical glucocorticoids unless the patient is unable to tolerate or is unwilling to use topical mesalamine.[6]

If the patient does not feel any relief after four weeks of therapy, mesalamine can be supplemented with other drug options such as an addition of topical or oral glucocorticoid, oral 5-ASA, budesonide multi-matrix, or a TNFα inhibitor depending on the severity of the disease.[7][5]

Mesalamine is also used in maintenance therapy for those who had more than one episode or flare-up per year, patients with ulcerative proctosigmoiditis, or ulcerative colitis that extends into the sigmoid colon. The use of topical mesalamine significantly decreases the risk of relapse.[6][7][8][4]

The exact mechanism of mesalamine is unknown. However, the hypothesis is that it modulates the inflammatory response derived from the cyclooxygenase and lipooxygenase pathways, thus decreasing the synthesis of prostaglandins and leukotrienes. Other potential mechanisms include interference with the production of inflammatory cytokines via decreasing the activity nuclear factor­ κB (NF-κB), and inhibition of tumor necrosis factor (TNF), cellular functions of mucosal lymphocytes, macrophages, and natural killer cells. Mesalamine has also been postulated to be a free radical scavenger and an antioxidant.[3][9]

Depending on the formulation of the drug, mesalamine can get released at different sites along the GI tract. For example, the 5-ASA delayed-release capsules can be released anywhere from the jejunum to the rectum, the 5-ASA pH-dependent release can be released anywhere from the ileum to the rectum, Sulfasalazine (prodrug) can be released anywhere from the proximal colon to the rectum, 5-ASA enemas get released in the distal colon and rectum, and 5-ASA suppositories are released only in the rectum.[6][10]

Mesalamine can be taken orally as a capsule or a tablet with or without food. Some formulations are delayed-release or pH-dependent to target specific inflamed sites along the GI tract. The effectiveness of mesalamine depends on the concentration at the site of active disease and is thought to work topically.[4]

Mesalamine can also be administered rectally as an enema, foam, or a suppository. Topical formulations such as the suppository and the enema are preferable for the treatment of ulcerative colitis.[3]

Patients tolerate most mesalamine (5-ASA) formulations well. However, adverse effects may include nausea, GI upset, abdominal pain, headaches, nasopharyngitis, rash, arthralgias, agranulocytosis, aplastic anemia, myalgias, bone marrow suppression, oligospermia, hematuria, and cholestatic hepatitis. Renal impairment, including interstitial nephritis, nephrotic syndrome, and renal failure, can be seen and must be carefully monitored before initiating treatment and during treatment for these reasons.[4]

Hypersensitivity reactions are also common and have been reports on pericarditis, myocarditis, hepatitis, nephritis, pneumonitis, and hematology associated reactions. Patients may also be intolerant to mesalamine and cause symptoms such as cramping, headache, fever, malaise, pruritis, rash, and abdominal pain. Treatment must discontinue if such issues occur.

Drug interactions:

• Antacids: May disrupt the pH-dependent formulations of mesalamine. This condition can result in the premature release and a decrease in the therapeutic effect of mesalamine.
• Heparin: 5-ASA can enhance the pharmacologic effects of heparin and can subsequently increase the risk of bleeding or bruising.
• Cardiac glycosides: 5-ASA may decrease the concentration of cardiac glycosides in the blood.
• Myelosuppressive agents (e.g., mercaptopurine): Increase bone marrow suppression risk.
• H2 receptor blocker: May increase gastrointestinal pH and cause premature release of mesalamine and decrease its therapeutic effect.
• NSAIDs: Increases the risk of nephrotoxicity.
• Thiopurine analogs (e.g., mercaptopurine): Interaction with 5-ASA may decrease the metabolism of thiopurine analogs.
• Proton pump inhibitors: May increase gastrointestinal pH and cause premature release of mesalamine and decrease the therapeutic effect.
• Varicella vaccine: Increases risk of Reye syndrome and may enhance the toxic effects of these vaccines.[4]

Contraindications for mesalamine include hypersensitivity to mesalamine, salicylates, or aminosalicylates. Contraindications also include patients with severe renal or hepatic impairment due to the toxic nature of mesalamine in the kidneys and the liver. Other contraindications for the use of mesalamine are urinary tract obstruction, use in infants, and patients with existing gastric or duodenal ulcers.[4]