WARNINGS
ROWASA® 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.
PRECAUTIONS
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 steriod therapy
and two weeks later a pancolectomy was required.
Although renal abnormalities were not noted in the clinical
trials with ROWASA® 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® suspension
enema, especially those on concurrent oral products which
liberate mesalamine and those with preexisting renal disease,
should be carefully monitored with urinalysis, BUN 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® Rectal Suspension Enema some patients
have developed pancolitis. However, extension of upper
disease boundary and/or flare-ups occurred less often
in the ROWASA® suspension enema treated group than
in the placebo-treated group.
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® 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®
Rectal Suspension Enema should be investigated with this
information in mind. Discontinuation of ROWASA® 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 two-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
have not been reported 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.
Nursing Mothers
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.
Pediatric Use
Safety and effectiveness in pediatric patients
have not been established.
| 
