A Nonsteroidal Anti-Inflammatory Drug; NSAID
as Reported by Physician's Desk Reference® (1)
Gastrointestinal (GI) Effects - Risk of GI Ulceration,
Bleeding, and Perforation:
Serious gastrointestinal toxicity such as inflammation, bleeding, ulceration,
and perforation of the stomach, small intestine or large intestine, can
occur at any time, with or without warning symptoms, in patients treated
with nonsteroidal anti-inflammatory drugs (NSAIDs). Minor upper gastrointestinal
problems, such as dyspepsia, are common and may also occur at any time
during NSAID therapy. Therefore, physicians and patients should remain
alert for ulceration and bleeding even in the absence of previous GI tract
symptoms. Patients should be informed about the signs and/or symptoms
of serious GI toxicity and the steps to take if they occur. The utility
of periodic laboratory monitoring has not been demonstrated, nor has it
been adequately assessed. Only one in five patients, who develop a serious
upper GI adverse event on NSAID therapy, is symptomatic. It has been demonstrated
that upper GI ulcers, gross bleeding or perforation, caused by NSAIDs,
appear to occur in approximately 1% of patients treated for 3-6 months,
and in about 2%-4% of patients treated for one year. These trends continue
thus, increasing the likelihood of developing a serious GI event at some
time during the course of therapy. However,
even short term therapy is not without risk.
Information for Patients
Cataflam, like other drugs of its class, can cause discomfort and, rarely,
more serious side effects, such as gastrointestinal bleeding, which may
result in hospitalization and even fatal outcomes. Although serious GI
tract ulcerations and bleeding can occur without warning symptoms, patients
should be alert for the signs and symptoms of ulcerations and bleeding,
and should ask for medical advice when observing any indicative sign or
symptoms. Patients should be apprised of the importance of this follow-up.
Patients should report to their physicians signs or symptoms of gastrointestinal
ulceration or bleeding, skin rash, weight gain, or edema.
Patients should be informed of the warning signs and symptoms of hepatotoxicity
(e.g., nausea, fatigue, lethargy, pruritus, jaundice, right upper quadrant
tenderness, and "flu-like" symptoms). If these occur, patients
should be instructed to stop therapy and seek immediate medical therapy.
Patients should also be instructed to seek immediate emergency help in
the case of an anaphylactoid reaction.
In late pregnancy, as with other NSAIDs, Cataflam should be avoided because
it will cause premature closure of the ductus arteriosus.
Patients on long-term treatment with NSAIDs, should have their CBC and
a chemistry profile (including transaminases) checked periodically. If
clinical signs and symptoms consistent with liver or renal disease develop,
systemic manifestations occur (e.g., eosinophilia, rash, etc.) or if abnormal
liver tests persist or worsen, Cataflam should be discontinued.
Aspirin: When Cataflam is administered
with aspirin, its protein binding is reduced. The clinical significance
of this interaction is not known; however, as with other NSAIDs, concomitant
administration of diclofenac and aspirin is not generally recommended
because of the potential of increased adverse effects.
Methotrexate: NSAIDs have been reported
to competitively inhibit methotrexate accumulation in rabbit kidney
slices. This may indicate that they could enhance the toxicity of methotrexate.
Caution should be used when NSAIDs are administered concomitantly with
Cyclosporine: Cataflam, like other NSAIDs,
may affect renal prostaglandins and increase the toxicity of certain
drugs. Therefore, concomitant therapy with Cataflam may increase cyclosporine's
nephrotoxicity. Caution should be used when Cataflam is administered
concomitantly with cyclosporine.
ACE-inhibitors: Reports suggest that NSAIDs
may diminish the antihypertensive effect of ACE-inhibitors. This interaction
should be given consideration in patients taking NSAIDs concomitantly
Furosemide: Clinical studies, as well
as post-marketing observations, have shown that Cataflam can reduce
the natriuretic effect of furosemide and thiazides in some patients.
This response has been attributed to inhibition of renal prostaglandin
synthesis. During concomitant therapy with NSAIDs, the patient should
be observed closely for signs of renal failure (see PRECAUTIONS - Renal
Effects ), as well as to assure diuretic efficacy.
Lithium: NSAIDs have produced an elevation
of plasma lithium levels and a reduction in renal lithium clearance.
The mean minimum lithium concentration increased 15% and the renal clearance
was decreased by approximately 20%. These effects have been attributed
to inhibition of renal prostaglandin synthesis by the NSAID. Thus, when
NSAIDs and lithium are administered concurrently, subjects should be
observed carefully for signs of lithium toxicity.
Warfarin: The effects of warfarin and
NSAIDs on GI bleeding are synergistic, such that users of both drugs
together have a risk of serious GI bleeding higher than users of either
Teratogenic Effects: Pregnancy Category
C. Reproductive studies conducted in rats and rabbits have not demonstrated
evidence of developmental abnormalities. However, animal reproduction
studies are not always predictive of human response. There are no adequate
and well-controlled studies in pregnant women.
Nonteratogenic Effects: Because of the known
effects of nonsteroidal anti-inflammatory drugs on the fetal cardiovascular
system (closure of ductus arteriosus), use during pregnancy (particularly
late pregnancy) should be avoided.
Labor and Delivery
In rat studies with NSAIDs, as with other drugs known to inhibit prostaglandin
synthesis, an increased incidence of dystocia, delayed parturition, and
decreased pup survival occurred. The effects of Cataflam on labor and
delivery in pregnant women are unknown.
It is not known whether this drug is excreted in human milk. Because many
drugs are excreted in human milk and because of the potential for serious
adverse reactions in nursing infants from Cataflam, a decision should
be made whether to discontinue nursing or to discontinue the drug, taking
into account the importance of the drug to the mother.
Safety and effectiveness in pediatric patients have not been established.
As with any NSAIDs, caution should be exercised in treating the elderly
(65 years and older).
In 718 patients treated for shorter periods, i.e., 2 weeks or less, with
Cataflam ® (diclofenac potassium immediate-release tablets), adverse
reactions were reported one-half to one-tenth as frequently as by patients
treated for longer periods. In a 6-month, double-blind trial comparing
Cataflam (N=196) versus Voltaren ® (diclofenac sodium delayed-release
tablets) (N=197) versus ibuprofen (N=197), adverse reactions were similar
in nature and frequency.
In patients taking Cataflam or other NSAIDs, the most frequently reported
adverse experiences occurring in approximately 1%-10% of patients are:
Gastrointestinal experiences including: abdominal pain, constipation,
diarrhea, dyspepsia, flatulence, gross bleeding/perforation, heartburn,
nausea, GI ulcers (gastric/duodenal) and vomiting.
Abnormal renal function, anemia, dizziness, edema, elevated liver enzymes,
headaches, increased bleeding time, pruritus, rashes and tinnitus.
Additional adverse experiences reported occasionally include:
Body as a Whole: fever, infection, sepsis
Cardiovascular System: congestive heart failure, hypertension, tachycardia,
Digestive System: dry mouth, esophagitis, gastric/peptic ulcers, gastritis,
gastrointestinal bleeding, glossitis, hematemesis, hepatitis, jaundice
Hemic and Lymphatic System: ecchymosis, eosinophilia, leukopenia, melena,
purpura, rectal bleeding, stomatitis, thrombocytopenia
Metabolic and Nutritional: weight changes
Nervous System: anxiety, asthenia, confusion, depression, dream abnormalities,
drowsiness, insomnia, malaise, nervousness, paresthesia, somnolence,
Respiratory System: asthma, dyspnea
Skin and Appendages: alopecia, photosensitivity, sweating increased
Special Senses: blurred vision
Urogenital System: cystitis, dysuria, hematuria, interstitial nephritis,
oliguria/polyuria, proteinuria, renal failure
Other adverse reactions, which occur rarely are:
Body as a Whole: anaphylactic reactions, appetite changes, death
Cardiovascular System: arrhythmia, hypotension, myocardial infarction,
Digestive System: colitis, eructation, liver failure, pancreatitis
Hemic and Lymphatic System: agranulocytosis, hemolytic anemia, aplastic
anemia, lymphadenopathy, pancytopenia
Metabolic and Nutritional: hyperglycemia
Nervous System: convulsions, coma, hallucinations, meningitis
Respiratory System: respiratory depression, pneumonia
Skin and Appendages: angioedema, toxic epidermal necrolysis, erythema
multiforme, exfoliative dermatitis, Stevens-Johnson syndrome, urticaria
Special Senses: conjunctivitis, hearing impairment.
All traditional NSAIDs can cause stomach ulcers or internal bleeding
without warning. Consultation with your doctor and regular check ups
are important when taking NSAIDs.