WARNINGS AND PRECAUTIONS
Renal Impairment
Renal impairment, including minimal change nephropathy,
acute and chronic interstitial nephritis, and, rarely, renal
failure, has been reported in patients given products such as
APRISO that contain mesalamine or are converted to
mesalamine.
It is recommended that patients have an evaluation of
renal function prior to initiation of APRISO therapy and
periodically while on therapy. Exercise caution when using
APRISO in patients with known renal dysfunction or a history of
renal disease.
In animal studies, the kidney was the principal organ for
toxicity
[See Nonclinical
Toxicology (
13.2
)]
Mesalamine-Induced Acute Intolerance Syndrome
Mesalamine has been associated with an acute intolerance
syndrome that may be difficult to distinguish from a flare of
inflammatory bowel disease. Although the exact frequency of
occurrence has not been determined, it has occurred in
3% of patients in controlled clinical trials of
mesalamine or sulfasalazine. Symptoms include cramping, acute
abdominal pain and bloody diarrhea, sometimes fever, headache,
and rash. If acute intolerance syndrome is suspected, promptly
discontinue treatment with APRISO.
Hypersensitivity
Some patients who have experienced a hypersensitivity
reaction to sulfasalazine may have a similar reaction to APRISO
capsules or to other compounds that contain or are converted to
mesalamine.
Hepatic Impairment
There have been reports of hepatic failure in patients
with pre-existing liver disease who have been administered
mesalamine. Caution should be exercised when administering
APRISO to patients with liver disease.
USE IN SPECIFIC POPULATIONS
Pregnancy
Pregnancy Category B. Reproduction studies with
mesalamine have been performed in rats at oral doses up to 320
mg/kg/day (about 1.7 times the recommended human dose based on a
body surface area comparison) and rabbits at doses up to 495
mg/kg/day (about 5.4 times the recommended human dose based on a
body surface area comparison) and have revealed no evidence of
impaired fertility or harm to the fetus due to
mesalamine. There are, however, no adequate and
well-controlled studies in pregnant women. Because
animal reproduction studies are not always predictive of human
response, this drug should be used during pregnancy only if
clearly needed.
Mesalamine is known to cross the placental
barrier.
Nursing Mothers
Low concentrations of mesalamine and higher
concentrations of its N-acetyl metabolite have been detected in
human breast milk. The clinical significance of this
has not been determined and there is limited experience of
nursing women using mesalamine. Caution should be
exercised when APRISO is administered to a nursing
woman.
Pediatric Use
Safety and effectiveness of APRISO capsules in pediatric
patients have not been established.
Geriatric Use
Clinical studies of APRISO did not include sufficient
numbers of subjects aged 65 and over to determine whether they
respond differently than younger subjects. Other
reported clinical experience has not identified differences in
responses between elderly and younger patients. In
general, the greater frequency of decreased hepatic, renal, or
cardiac function, and of concomitant disease or other drug
therapy in elderly patients should be considered when
prescribing APRISO.
Reports from uncontrolled clinical studies and
postmarketing reporting systems suggested a higher incidence of
blood dyscrasias, i.e., neutropenia, pancytopenia, in patients
who were 65 years or older who were taking mesalamine-containing
products such as APRISO. Caution should be taken to
closely monitor blood cell counts during mesalamine
therapy.
Mesalamine is known to be substantially excreted by the
kidney, and the risk of adverse reactions to this drug may be
greater in patients with impaired renal
function. Because elderly patients are more likely to
have decreased renal function, care should be taken when
prescribing this drug therapy.
[see Warning and Precautions
(
5.1
)]
.
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