What Is the Maximum Dose of Mesalamine for Ulcerative Colitis?

Julie M. Sease, PharmD, BCPS


August 15, 2008


What is the maximum daily dose of mesalamine when administered both orally and topically for ulcerative colitis?

Response From the Expert


Julie M. Sease, PharmD, BCPS
Clinical Assistant Professor, Department of Clinical Pharmacy and Outcomes Sciences, South Carolina College of Pharmacy, Columbia, South Carolina; Clinical Pharmacy Specialist, William Jennings Bryan Dorn VA Medical Center, Columbia, South Carolina


Mesalamine is an aminosalicylate (5-aminosalicylate, 5-ASA) given orally or rectally for ulcerative colitis (UC).[1] The utility of mesalamine may be due to decreased production of prostaglandins and leukotrienes at the site of disease by inhibition of cyclooxygenase and lipoxygenase pathways.[1]

Mesalamine is considered safe for both short- and long-term treatment of UC, having dose-response efficacy without dose-related toxicity.[1] The anti-inflammatory effect of mesalamine is closely linked to its mucosal concentration.[2] Therefore, mesalamine is available in many dosage forms with the intent to provide local absorption. Systemic effects are minimized secondary to local action on the gastric mucosa. Commonly reported adverse effects include headache, diarrhea, bloating, and nausea. Adverse effects (eg, hematologic) are uncommon.

Several trials have evaluated the combination of oral and topical mesalamine for patients with ulcerative proctitis and extensive UC involving the distal left-sided colon.

Eighteen patients with pancolitis or left colitis in clinical remission with a 2-year history of moderate-to-severe relapses were evaluated during a 2-year longitudinal study.[2] Treatment consisted of increasing oral mesalamine treatment to 3.2-4.8 g daily (baseline, 2.4-3.2 g daily) and adding topical mesalamine (by enema) 4 g daily. After 6 months, the enema was decreased to 3 times weekly. Patients had significantly fewer UC relapses during combination therapy compared with the previous 2 years during oral mesalamine monotherapy. No courses of steroids or hospitalization were needed during combination treatment. Higher rectal mucosal mesalamine concentrations were detected after 1 year of combination therapy as compared with oral therapy alone. Finally, no side effects due to therapy occurred during the trial.

The Rowasa Study Group evaluated 60 patients with mild-to-moderate distal ulcerative colitis in a 6-week, multicenter, randomized, double-blind trial.[3] Patients received mesalamine 800 mg 3 times daily, mesalamine 4 g by rectal enema every evening, or both. Combination therapy resulted in greater improvement in disease activity index scores compared with either oral or rectal mesalamine monotherapy after 6 weeks. Patients receiving combination therapy reported an absence of rectal bleeding significantly sooner. The highest percentage of patients reporting no rectal bleeding consisted of the combination therapy patients.

A randomized, double-blind study examined 127 patients with extensive mild-to-moderate active UC who were taking 2 g of oral mesalamine twice daily for 8 weeks.[4] During the first 4 weeks, patients were randomized to receive either a 1 g mesalamine enema or placebo at bedtime. The combination therapy group had higher remission rates at both 4 and 8 weeks. Adverse effects were considered mild to moderate and were similar for both groups.

Combination oral plus rectal mesalamine administration has demonstrated superior efficacy compared with oral monotherapy in patients with mild-to-moderate UC. [2,3,4] Doses of up to 4.8 g per day of oral mesalamine in combination with up to 4 g of mesalamine administered rectally have demonstrated efficacy without serious adverse effects.[2] Larger studies are needed to establish optimal dosing and duration of mesalamine combination therapy.


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