A closer look at new FDA actions: Shire Pharmaceutical's Lialda

Shire Pharmaceutical?s LialdaShire Pharmaceutical's mesalamine (Lialda) has received approval from the FDA as the first once-daily treatment for inducing remission of mild-to-moderate ulcerative colitis (UC) in adults.^{1,2 Traditional first-line treatments for UC carry a heavy pill burden?regimens can be dosed 2 to 4 times daily and may total up to 16 pills a day. Previous studies concluded noncompliant patients to be at a five-fold greater risk for UC exacerbations than compliant patients.}3Mesalamine's once-daily dosing is a result of the tablet's MMX technology. This delivery system uses a pH-dependent, gastro-resistant coating to delay the medication's release until the tablet reaches the colon.3UC is a chronic inflammatory autoimmune disease of the bowel that creates sores or ulcerations inside the large intestine. The disease is usually diagnosed between ages 15 and 30 and often displays symptoms such as severe abdominal pain, bloody diarrhea that may be frequent or uncontrollable, fatigue, and weight loss.3 Patients with UC are at an increased risk for developing colon cancer.^{3,4 An estimated 700,000 Americans have the condition.}3Mechanism of Action Like other members of the aminosalicylate class, the exact mechanism of mesalamine is not known. It is believed to act topically to reduce inflammation in the colon by blocking cyclooxygenase and inhibiting the production of prostaglandin in the colon. Mesalamine also may inhibit the activation of a nuclear transcription factor responsible for the genes of proinflammatory proteins.1Clinical TrialsTwo randomized, double-blind, placebo-controlled trials evaluated the safety and efficacy of mesalamine in the induction of remission in adult patients with UC.1The first study of 262 patients compared either mesalamine 2.4 g given twice a day or 4.8 g given once a day with placebo. The second study of 255 patients compared mesalamine 2.4 g given once a day or 4.8 g given once a day with placebo. Both studies lasted 8 weeks, and at the end of each study, mesalamine was determined to be superior to placebo.1,2Dosage Mesalamine can be given as either 2.4 or 4.8 g once daily with a meal for up to 8 weeks. The tablet should be swallowed whole; any disruption to the tablet's integrity may affect its delayed-release mechanism.1Safety Mesalamine is contraindicated in patients with a known hypersensitivity to any of the components of mesalamine or to salicylates.1Caution should be used in patients with pyloric stenosis. Although most patients with an allergy to sulfasalazine are not sensitive to mesalamine, caution should be used in this population. Approximately 3% of patients in clinical trials of mesalamine or sulfasalazine have exhibited an acute intolerance syndrome. Symptoms of this syndrome include cramping, acute abdominal pain, bloody diarrhea, fever, headache, and rash and are often difficult to differentiate from a flare-up of UC. Should an acute intolerance syndrome occur, treatment with mesalamine should be stopped immediately. Other forms of mesalamine have been associated with mesalamine-induced cardiac hypersensitivity reactions such as myocarditis and pericarditis. Patients should have a baseline evaluation of renal function performed before beginning treatment and periodically thereafter, as mesalamine preparations and prodrugs have been associated with renal impairment. Mesalamine is not approved for pediatric use. Mesalamine is a pregnancy category B medication.1The most common adverse effects of mesalamine are headache and flatulence.3References

1. Lialda complete prescribing information. Lialda Web site. Available at: www.lialda.com/Professional/pdf/pi.pdf. Accessed May 2007.

2. LIALDA (mesalamine) with MMX technology?the first oral once-daily mesalamine for active, mild to moderate ulcerative colitis?now available [press release]. Philadelphia, Pa: Shire plc; March 19, 2007. Available at: http://ww7.investorrelations.co.uk/shire/uploads/press/shire/LIALDALaunch03072.pdf. Accessed May 2007.

3. Ulcerative colitis (UC) sufferers find UC quite disruptive to many aspects of daily life [press release]. Wayne, Pa: Shire plc; May 17, 2007. Available at: www.shire.com/shire/NewsAndMedia/PressReleases/showShirePress.jsp?ref=782&tn=3 &m1=8&m2=. Accessed May 2007.

4. About ulcerative colitis (UC). Lialda Web site. Available at: www.lialda.com/about/about.asp. Accessed May 2007.