Mesalamine

Mesalamine. Rowasa, Asacol, and Pentasa are trade names for mesalamine [89-57-6] (5-ASA, 5-amino-2-hydroxybenzoic acid). It is a white to pinkish crystalline substance that is slightly soluble in cold water and alcohol, more soluble in hot water, and soluble in hydrochloric acid. It may be prepared by the reduction of y -nitrobenzoic acid with zinc dust and HCl. 

The miscellaneous GI drugs include bismuth subsalicylate, mesalamine, misoprostol, olsalazine, sucralfate, and sulfasalazine... 

Bismudi subsalicylate is used in combination witii otiier dru > to treat gastric and duodenal ulcers caused by H. pylori bacteria Mesalamine is used in the treatment of chronic inflammatoiy bowel disease Misoprostol is used to prevent gastric ulcers in those taking aspirin or nonsteroidal anti-inflammatory dragp in high doses for a prolonged time Olsalazine is used in the treatment of ulcerative colitis in those allergic to sulfasalazine. Sulfasalazine is used in the treatment of Crohn s disease and ulcerative colitis. Sucralfate is used in the treatment of duodenal ulcer. 

Oral administration of mesalamine may cause abdominal pain, nausea, headache dizziness, fever, and weakness. The adverse reactions associated witii rectal administration are less than those seen witii oral administration, but headache abdominal discomfort, flu-like syndrome, and weakness may still occur. Olsalazine administration may result in diarrhea, abdominal discomfort, and nausea Sulfasalazine is a sulfonamide witii adverse reactions the same as for the sulfonamide drugs (see Chap. 6). 

Misoprostol is used cautiously in women of childbearing age. Mesalamine, olsalazine, sucralfate, and sulfasalazine are Pregnancy Category B drugs all are used with caution during pregnancy (safety has not been established) and lactation. 

Mesalamine—Swallow tablets whole do not chew them. For the suppository, remove foil wrapper and immediately insert tiie pointed end into the rectum without using force. For tiie suspension form, instructions are included with the product. Shake well, remove the protective sheath from the applicator tip, and gently insert the tip into the rectum. Partially intact tablets may be found in the stool if this occurs, notify the primary health care provider. 

Angiotensin converting enzyme inhibitors, azathioprine, mer-captopurine, mesalamine, sulfasalazine, sulfonamide antimicrobials, and tetracyclines... 

The prototypical aminosalicylate is sulfasalazine, which is comprised of mesalamine linked by a diazo bond to the carrier molecule sulfapyridine. This linkage prevents premature absorption of mesalamine in the small intestine. Once sulfasalazine is delivered to the colon, bacterial degradation of... 

Mesalamine Rowasa Enema 4 g/60 mL 4g Distal left colon and rectum... 

Newer mesalamine products utilize non-sulfapyridine methods for drug delivery. Olsalazine uses two mesalamine molecules linked together, while balsalazide uses the inert carrier molecule 4-aminobenzoyl-P-alanine. Both drugs use a diazo bond similar to sulfasalazine. Other mesalamine formulations are pH-dependent formulations that release mesalamine at various points throughout the GI tract. 

Treatment of acute episodes of ulcerative colitis is dictated by the severity and extent of disease, and first-line therapy of mild to moderate disease involves oral or topical aminosalicylate derivatives. Topical suppositories and enemas are preferred for active distal UC (left-sided disease and proctitis), as they deliver mesalamine directly to the site of inflammation. Topical mesalamine is superior to both topical corticosteroids and oral aminosalicylates for inducing remission in active mild to moderate UC.1,33,34 Enemas are appropriate for patients with... 

Proctitis Mesalamine suppository 1 g rectally daily May reduce suppository frequency to 1 g 3 times/week... 

Left-sided disease Mesalamine enema 1 g rectally daily, or Mesalamine 2.4-4.8 g/day or sulfasalazine 4-6 g/day orally May reduce enema frequency to 1 g every other day, or Taper to mesalamine 1.6-2.4 g/day or sulfasalazine 2-4 g/day orally... 

Proctitis Mesalamine suppository 1 g rectally daily If no response to mesalamine Prednisone 40-60 mg/day orally May reduce suppository frequency to 1 g 3 times/week taper prednisone as soon as possible Consider adding azathioprine or 6-MP 1.5-2.5 mg/kg per day orally... 

Disease x 7 days, or Infliximab 5 mg/kg IV at weeks 0, 2, and 6 If no response to IV corticosteroids or infliximab Cyclosporine 4 mg/kg per day IV possible Restart oral mesalamine or sulfasalazine May continue infliximab at maintenance doses of 5 mg/kg every 8 weeks... 

Topical mesalamine products provide a more rapid response than oral preparations. Improvement in symptoms may be seen in as little as 2 days, but 2 to 4 weeks of treatment may be necessary for maximal response. Response rates of up to 90% after 4 weeks of topical therapy have been reported, compared to 45% to 62% response rates with oral therapy.6,18 Oral and topical mesalamine preparations may be used together to provide maximal effect. Oral mesalamine may also be used for patients who are unwilling to use topical preparations. 

Topical corticosteroids are typically reserved for patients who do not respond to topical mesalamine. Patients should be properly educated regarding appropriate use of topical products. This includes proper administration and adequate retention of topical mesalamine products in order to maximize efficacy. 

For patients with more extensive disease extending proximal to the splenic flexure, oral sulfasalazine or any of the newer oral mesalamine products is considered first-line therapy.1 Doses should provide 4 to 6 g of sulfasalazine or 4.8 g of mesalamine. While little differences in efficacy exist between... 

Oral corticosteroids may be used for patients who are unresponsive to sulfasalazine or mesalamine. Prednisone doses of 40 to 60 mg per day (or equivalent) are recommended.1 Azathioprine or 6-MP is used for patients unresponsive to corticosteroids or those who become steroid-dependent. Over a 12-month period, these agents have been shown to reduce the relapse rate to 36% versus 59% seen with placebo.1 Infliximab 5 mg/kg may also be used for patients who are unresponsive to conventional oral therapies and may reduce the need for colectomy after 3 months of treatment.35... 

Patients with severe UC symptoms require hospitalization for management of their disease. If the patient is unresponsive to oral or topical mesalamine and oral corticosteroids, then a course of intravenous corticosteroids should be initiated.1 Hydrocortisone 300 mg/day given in three divided doses or methylprednisolone 60 mg daily for 7 to 10 days are the preferred therapies. 

Maintenance of remission of ulcerative colitis may be achieved with oral or topical aminosalicylates. Mesalamine suppositories 1 g daily may prevent relapse in up to 90% of patients with proctitis.1 Mesalamine enemas are appropriate for left-sided disease and may often be dosed three times weekly. Oral mesalamine at lower doses (e.g., 1.6 g per day) may be combined with topical therapies to maintain remission. Topical or oral corticosteroids are not effective for maintaining remission of distal UC and should be avoided. 

Oral sulfasalazine or mesalamine is effective in maintaining remission in patients with more extensive disease.1,26 Lower daily doses (e.g., 2 to 4 g sulfasalazine or 1.6 to 2.4 g mesalamine) may be used for disease maintenance. As with distal UC, oral corticosteroids are not effective for maintaining remission and should be avoided due to the high incidence of adverse effects. 

Induction of remission of mild to moderate active CD is accomplished with oral aminosalicylates. Sulfasalazine 4 to 6 g per day is most effective for patients with colonic involvement, with response rates of 50%.2,5 Mesalamine products have... 

A 57-year-old African-American man presents to the clinic for follow-up management of UC. He has had left-sided disease for 3 years and has been maintained in remission on maximal doses of oral mesalamine and prednisone 35 mg orally once daily. His provider has attempted several times to taper the prednisone dose, but the patient experiences a reappearance of symptoms if the dose is lowered below this level. Medical history is also significant for hypertension and heart failure. He has no known drug allergies. 

Azathioprine, mycophenolate mofetil, and enteric-coated MPA are not metabolized through the CYP isozyme system therefore, they do not experience the same DDI profiles as cyclosporine, tacrolimus, and sirolimus. Azathioprine s major DDIs involve allopurinol, angiotensin-converting enzyme (ACE) inhibitors, aminosalicylates (e.g., mesalamine and sulfasalazine), and warfarin.11 The interaction with allopurinol is seen frequently and has clinical significance. Allopurinol inhibits xanthine oxidase, the enzyme responsible for metabolizing azathioprine. Combination of azathioprine and allopurinol has resulted in severe toxicities, particularly myelosuppression. It is recommended that concomitant therapy with azathioprine and allopurinol be avoided, but if combination therapy is necessary, the azathioprine doses must be reduced to one-third or one-fourth of the current dose. Use of azathioprine with the ACE inhibitors or aminosalicylates also can result in enhanced myelosuppression.11 Some case reports exist demonstrating that warfarin s therapeutic effects may be decreased by azathioprine.43-45... 

Sulfasalazine, an agent that combines a sulfonamide (sulfapyridine) antibiotic and mesalamine (5-aminosahcyhc acid) in the same molecule, has been used for many years to treat IBD. Mesalamine-based products are listed in Table 26-5. 

Mesalamine Rowasa, Salofalk, Enema 1-4 g Rectum, termi-... 

Asacol Mesalamine tablet coated 2.4-4.8 g Distal ileum... 

Pentasa Mesalamine capsules encap- 2-4 g Small bowel... 

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