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.