Once-daily oral formulation of anti-inflammatory agent approved for the induction of remission in patients with active, mild-to-moderate ulcerative colitis
SHIREOnce-daily oral formulation of anti-inflammatory agent approved for the induction of remission in patients with active, mild-to-moderate ulcerative colitis
The mechanism of action of mesalamine is not fully understood. Patients with chronic inflammatory bowel disease have increased mucosal production of arachidonic acid metabolites through both the cyclooxygenase and lipoxygenase pathways; mesalamine may decrease inflammation by blocking cyclooxygenase and inhibiting prostaglandin production in the colon. Mesalamine may also inhibit the activation of nuclear factor-kappa B, which regulates the transcription of many genes for pro-inflammatory proteins. This new once-daily oral formulation of mesalamine was approved on January 16, 2007, for the induction of remission in patients with active, mild-to-moderate ulcerative colitis.
Safety. Mesalamine is contraindicated in patients with hypersensitivity to salicylates. Caution should be used in treating patients who are allergic to sulfasalazine. Patients with pyloric stenosis may experience prolonged gastric retention of mesalamine, which could delay the release of the drug in the colon. Treatment with mesalamine has been associated with an acute intolerance syndrome, the symptoms of which can include cramping, acute abdominal pain, bloody diarrhea, fever, headache, and rash. This syndrome may be difficult to distinguish from a flare-up of inflammatory bowel disease. If this syndrome is suspected, mesalamine treatment should immediately be discontinued. Cardiac hypersensitivity reactions (myocarditis and pericarditis) have been reported in patients treated with other mesalamine formulations. Caution should be exercised in the treatment of patients with conditions predisposing them to the development of myocarditis or pericarditis. Renal impairment, including minimal change nephropathy, and acute or chronic interstitial nephritis have also been reported in patients treated with mesalamine or prodrugs of mesalamine. Caution should be used in treating patients with known renal dysfunction; treatment should be initiated only if the benefits outweigh the risks. Patients should have an evaluation of renal function before initiation of therapy and periodically during treatment. Patients treated concurrently with nephrotoxic agents, including nonsteroidal anti-inflammatory drugs, may have an increased risk of renal reactions. Patients being treated concurrently with azathioprine or 6-mercaptopurine and mesalamine may have an increased risk of blood disorders. Caution is recommended in the treatment of patients with hepatic impairment. The most common adverse events associated with once-daily mesalamine treatment include headache, flatulence, increased alanine aminotransferase, alopecia, and pruritus.
Dosing. The recommended dose of this formulation of mesalamine for the induction of remission in adult patients with mild, active-to-moderate ulcerative colitis is two to four 1.2-g tablets (total dose, 2.4–4.8 g) taken once daily with a meal. Clinical trials with this dosage evaluated a treatment duration of ≤8 weeks. The safety and efficacy of treatment with this agent for >8 weeks have not been established.