ROWASA® (Mesalamine) Rectal Suspension Enema contains potassium metabisulfite, a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown but probably low. Sulfite sensitivity is seen more frequently in asthmatic or in atopic nonasthmatic persons. Epinephrine is the preferred treatment for serious allergic or emergency situations even though epinephrine injection contains sodium or potassium metabisulfite with the above-mentioned potential liabilities. The alternatives to using epinephrine in a life-threatening situation may not be satisfactory. The presence of a sulfite(s) in epinephrine injection should not deter the administration of the drug for treatment of serious allergic or other emergency situations.
Mesalamine has been implicated in the production of an acute intolerance syndrome characterized by cramping, acute abdominal pain and bloody diarrhea, sometimes fever, headache and a rash; in such cases prompt withdrawal is required. The patient's history of sulfasalazine intolerance, if any, should be re-evaluated. If a rechallenge is performed later in order to validate the hypersensitivity it should be carried out under close supervision and only if clearly needed, giving consideration to reduced dosage. In the literature one patient previously sensitive to sulfasalazine was rechallenged with 400 mg oral mesalamine; within eight hours she experienced headache, fever, intensive abdominal colic, profuse diarrhea and was readmitted as an emergency. She responded poorly to steroid therapy and two weeks later a pancolectomy was required.
Although renal abnormalities were not noted in the clinical trials with ROWASA® (Mesalamine) Rectal Suspension Enema, the possibility of increased absorption of mesalamine and concomitant renal tubular damage as noted in the preclinical studies must be kept in mind. Patients on ROWASA® (Mesalamine) Rectal Suspension Enema, especially those on concurrent oral products which liberate mesalamine and those with preexisting renal disease, should be carefully monitored with urinalysis, BUN (blood urea nitrogen), and creatinine studies.
In a clinical trial most patients who were hypersensitive to sulfasalazine were able to take mesalamine enemas without evidence of any allergic reaction. Nevertheless, caution should be exercised when mesalamine is initially used in patients known to be allergic to sulfasalazine. These patients should be instructed to discontinue therapy if signs of rash or fever become apparent.
While using ROWASA® (Mesalamine) Rectal Suspension Enema, some patients have developed pancolitis. However, extension of upper disease boundary and/or flare-ups occurred less often in the ROWASA® (Mesalamine) Rectal Suspension Enema treated group than in the placebo-treated group.
Worsening of colitis or symptoms of inflammatory bowel disease, including melena and hematochezia, may occur after commencing mesalamine.
Rare instances of pericarditis have been reported with mesalamine containing products including sulfasalazine. Cases of pericarditis have also been reported as manifestations of inflammatory bowel disease. In the cases reported with ROWASA® (Mesalamine) Rectal Suspension Enema, there have been positive rechallenges with mesalamine or mesalamine containing products. In one of these cases, however, a second rechallenge with sulfasalazine was negative throughout a 2-month follow-up. Chest pain or dyspnea in patients treated with ROWASA® (Mesalamine) Rectal Suspension Enema should be investigated with this information in mind. Discontinuation of ROWASA® (Mesalamine) Rectal Suspension Enema may be warranted in some cases, but rechallenge with mesalamine can be performed under careful clinical observation should the continued therapeutic need for mesalamine be present.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Mesalamine caused no increase in the incidence of neoplastic lesions over controls in a 2-year study of Wistar rats fed up to 320 mg/kg/day of mesalamine admixed with diet. Mesalamine is not mutagenic to Salmonella typhimurium tester strains TA98, TA100, TA1535, TA1537, TA1538. There were no reverse mutations in an assay using E. coli strain WP2UVRA. There were no effects in an in vivo mouse micronucleus assay at 600 mg/kg and in an in vivo sister chromatid exchange at doses up to 610 mg/kg. No effects on fertility were observed in rats receiving up to 320 mg/kg/day. The oligospermia and infertility in men associated with sulfasalazine has very rarely been reported among patients treated with mesalamine.
Pregnancy (Category B)
Teratologic studies have been performed in rats and rabbits at oral doses up to five and eight times respectively, the maximum recommended human dose, and have revealed no evidence of harm to the embryo or the fetus. There are, however, no adequate and well-controlled studies in pregnant women for either sulfasalazine or 5-ASA. Because animal reproduction studies are not always predictive of human response, 5-ASA should be used during pregnancy only if clearly needed.
It is not known whether mesalamine or its metabolite(s) are excreted in human milk. As a general rule, nursing should not be undertaken while a patient is on a drug since many drugs are excreted in human milk.
Safety and effectiveness in pediatric patients have not been established.