Approved Drug Label (PDF)
4
Contraindications
(Additions and/or
revisions underlined)
DIPENTUM
is contraindicated in patients with known or suspected hypersensitivity to salicylates, aminosalicylates
or their metabolites, or to any of the excipients in DIPENTUM.
5
Warnings and Precautions
PRECAUTIONS
(Additions and/or
revisions underlined)
Hepatic Failure
There
have been reports
of hepatic failure in patients with pre-existing liver disease who have been
administered mesalamine. Because olsalazine is converted to mesalamine,
evaluate the risks and benefits of using DIPENTUM in patients with known liver
impairment.
Photosensitivity
Patients
with pre-existing skin conditions such as atopic dermatitis and atopic eczema
have
reported more severe photosensitivity reactions. Advise patients to avoid
sun exposure, wear protective clothing, and use a broad-spectrum sunscreen when
outdoors.
Nephrolithiasis
Cases
of nephrolithiasis have been reported with the use of mesalamine, the active
moiety in DIPENTUM, including stones with 100% mesalamine content.
Mesalamine-containing stones are radiotransparent and undetectable by standard
radiography or computed tomography (CT). Ensure adequate hydration during treatment.
Interference
with Laboratory Tests
Use
of DIPENTUM, which is converted to mesalamine, may lead to
spuriously elevated test results when measuring urinary normetanephrine by
liquid chromatography with electrochemical detection because of the similarity
in the chromatograms of normetanephrine and mesalamine’s main metabolite,
N-acetyl-5-aminosalicylic acid (N-Ac-5-ASA). Consider an alternative, selective
assay for normetanephrine.
WARNINGS
(Newly added
section)
Renal
Impairment
Renal
impairment, including minimal change disease, acute and chronic interstitial
nephritis, and renal failure have been reported in patients given products that
contain mesalamine or are converted to mesalamine. In animal studies, the
kidney was the principal organ of mesalamine toxicity.
Evaluate
the risks and benefits of using DIPENTUM in patients with known renal
impairment or a history of renal disease or taking concomitant nephrotoxic
drugs. Mesalamine is known to be substantially excreted by the kidney, and the
risk of adverse reactions may be greater in patients with impaired renal
function. Evaluate renal function in all patients prior to initiation and
periodically while on DIPENTUM therapy.
Mesalamine-Induced Acute
Intolerance Syndrome
Olsalazine
is converted to mesalamine, which has been associated with an acute intolerance
syndrome that may be difficult to distinguish from an exacerbation of
ulcerative colitis.
Symptoms
include cramping, acute abdominal pain and bloody diarrhea, sometimes fever,
headache, and rash. Monitor patients for worsening of these symptoms while on
treatment. If acute intolerance syndrome is suspected, promptly discontinue
treatment with DIPENTUM.
Hypersensitivity Reactions
Some
patients who have experienced a hypersensitivity reaction to sulfasalazine may
have a similar reaction to DIPENTUM or to other compounds that contain or are
converted to mesalamine. Mesalamine-induced hypersensitivity reactions may
present as internal organ involvement, including myocarditis, pericarditis,
nephritis, hepatitis, pneumonitis, and hematologic abnormalities. Evaluate
patients immediately if signs or symptoms of a hypersensitivity reaction are
present. Discontinue DIPENTUM if an alternative etiology for the signs and
symptoms cannot be established.
6
Adverse Reactions
(Additions and/or
revisions underlined)
Olsalazine
has been evaluated in ulcerative colitis patients in remission, as well as
those with acute disease. Both sulfasalazine-tolerant and intolerant patients
have been studied in controlled clinical trials. Overall, 10.4% of patients
discontinued olsalazine because of an adverse experience compared with 6.7% of
placebo patients. The most commonly reported adverse reactions leading to
treatment withdrawal were diarrhea or loose stools (olsalazine 5.9%; placebo
4.8%), abdominal pain, and rash or itching (slightly more than 1% of patients
receiving olsalazine).
Diarrhea
Overall,
approximately 17% of subjects receiving olsalazine in clinical studies reported
diarrhea sometime during therapy. This diarrhea resulted in withdrawal of
treatment in 6% of patients. This diarrhea appears to be dose related, although
it may be difficult to distinguish from the underlying symptoms of the disease.
…
Postmarketing
The
following events have been identified during post-approval use of products that
contain (or are metabolized to) mesalamine in clinical practice. Because they
are reported voluntarily from a population of unknown size, estimates of
frequency cannot be made. These events have been chosen for inclusion due to a
combination of seriousness, frequency of reporting, or potential causal
connection to mesalamine:
Blood
and Lymphatic System Disorders
Aplastic
anemia, Pancytopenia
General
Disorders and Administration Site Conditions
Pyrexia
Hepatobiliary
Disorders
Hepatic
enzyme increased, Hepatitis, Increased bilirubin
Reports
of hepatotoxicity, including elevated liver function tests (SGOT/AST, SGPT/ALT,
GGT, LDH, alkaline phosphatase, bilirubin), jaundice, cholestatic jaundice,
cirrhosis, and possible hepatocellular damage including liver necrosis and
liver failure. Some of these cases were fatal. One case of Kawasaki-like
syndrome, which included hepatic function changes, was also reported.
Musculoskeletal
and Connective Tissue Disorders
Myalgia
Respiratory,
Thoracic and Mediastinal Disorders
Dyspnea,
Interstitial lung disease
Skin
and Subcutaneous Tissue Disorders
Angioneurotic
edema
Nervous
System Disorders
Paresthesia,
Peripheral neuropathy
Renal
and Urinary Disorders
Interstitial
nephritis, nephrolithiasis
7
Drug Interactions
(Additions and/or
revisions underlined)
Nephrotoxic
Agents, Including Non-Steroidal Anti-Inflammatory Drugs
The
concurrent use of mesalamine with known nephrotoxic agents, including
non-steroidal anti-inflammatory drugs (NSAIDs), may increase the risk of nephrotoxicity.
Monitor patients taking nephrotoxic drugs for changes in renal function and
mesalamine-related adverse reactions.
Azathioprine
or 6-Mercaptopurine
The
concurrent use of mesalamine with azathioprine or 6-mercaptopurine and/or any
other drugs known to cause myelotoxicity (e.g., thioguanine) may increase the
risk for blood disorders, bone marrow failure, and associated complications. If
concomitant use of DIPENTUM and azathioprine or 6-mercaptopurine cannot be
avoided, monitor blood tests, including complete blood cell counts and platelet
counts.
Low
Molecular Weight Heparins or Heparinoids
The
co-administration of salicylates and low molecular weight heparins or
heparinoids may result in an increased risk of bleeding (i.e., hematomas)
following neuraxial anesthesia. Salicylates should be discontinued prior to the
initiation of a low molecular weight heparin or heparinoid. If this is not possible, it is recommended to
monitor patients closely for bleeding.
Warfarin
Increased
prothrombin time in patients taking concomitant warfarin has been reported.
Monitor INR and prothrombin time and adjust the dosage of warfarin, as
needed with concomitant use of DIPENTUM, to maintain the target
INR range.
Varicella
Vaccine
It
is recommended not to give salicylates for six weeks after the varicella
vaccine to avoid a possible increased risk of developing Reye’s syndrome.
8
Use in Specific Populations
Geriatric Use
(Additions and/or
revisions underlined)
Clinical
studies of DIPENTUM did not include sufficient numbers of subjects aged 65 and
over to determine whether they respond differently from younger subjects. Reports
from uncontrolled clinical studies and postmarketing reporting systems
suggested a higher incidence of blood dyscrasias (i.e., agranulocytosis,
neutropenia and pancytopenia) in patients receiving mesalamine-containing
products such as DIPENTUM who were 65 years or older compared to younger
patients.
Consider
monitoring of complete blood cell counts and platelet counts in elderly
patients during treatment with DIPENTUM, especially if used concomitantly with
anticoagulants. In general, consider the greater frequency of decreased
hepatic, renal, or cardiac function, and of concurrent disease or other drug
therapy in elderly patients when prescribing DIPENTUM.
Hepatic
(Additions and/or
revisions underlined)
There
have been reports of hepatic failure in patients with pre-existing liver
disease who have been administered other products containing mesalamine.
Evaluate the risks and benefits of using DIPENTUM in patients with known liver
impairment.
Renal
(Additions and/or
revisions underlined)
Mesalamine
is known to be substantially excreted by the kidney, and the risk of adverse
reactions to DIPENTUM, which is converted to mesalamine, may be greater in
patients with impaired renal function. Evaluate renal function in all patients
prior to initiation and periodically while on DIPENTUM therapy. Monitor
patients with known renal impairment or history of renal disease or taking
nephrotoxic drugs for decreased renal function and mesalamine-related adverse reactions.
Get Email Alerts |
Guide
