Carefully consider the potential benefits and risks of CATAFLAM and other treatment options before deciding to use CATAFLAM. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals.

CATAFLAM is indicated:

• For treatment of primary dysmenorrhea
• For relief of mild to moderate pain
• For relief of the signs and symptoms of osteoarthritis
• For relief of the signs and symptoms of rheumatoid arthritis

Nonsteroidal anti-inflammatory drugs (NSAIDs) cause an increased risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, which can be fatal. This risk may occur early in treatment and may increase with duration of use.

CATAFLAM is contraindicated in the setting of coronary artery bypass graft (CABG) surgery.

CATAFLAM is contraindicated in patients with a history of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs. Severe, sometimes fatal, anaphylactic reactions to NSAIDs have been reported in such patients.

NSAIDs cause an increased risk of serious gastrointestinal (GI) adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Elderly patients and patients with a prior history of peptic ulcer disease and/or GI bleeding are at greater risk for serious GI events.

Patients with a prior history of peptic ulcer disease and/or GI bleeding who use NSAIDs had a greater than 10-fold increased risk for developing a GI bleed compared to patients without these risk factors. Other factors that increase the risk of GI bleeding in patients treated with NSAIDs include longer duration of NSAID therapy, concomitant use of oral corticosteroids, aspirin, anticoagulants, or selective serotonin reuptake inhibitors (SSRIs); smoking, use of alcohol, older age, and poor general health status. Most postmarketing reports of fatal GI events occurred in elderly or debilitated patients. Additionally, patients with advanced liver disease and/or coagulopathy are at increased risk for GI bleeding.

Strategies to Minimize the GI Risks in NSAID-treated patients:

• Use the lowest effective dosage for the shortest possible duration
• Avoid administration of more than one NSAID at a time
• Avoid use in patients at higher risk unless benefits are expected to outweigh the increased risk of bleeding. For such patients, as well as those with active GI bleeding, consider alternate therapies other than NSAIDs
• Remain alert for signs and symptoms of GI ulceration and bleeding during NSAID therapy
• If a serious GI adverse event is suspected, promptly initiate evaluation and treatment, and discontinue CATAFLAM until a serious GI adverse event is ruled out
• In the setting of concomitant use of low-dose aspirin for cardiac prophylaxis, monitor patients more closely for evidence of GI bleeding

Clinical trials of several COX-2 selective and nonselective NSAIDs of up to three years duration have shown an increased risk of serious cardiovascular (CV) thrombotic events, including myocardial infarction (MI) and stroke, which can be fatal. Based on available data, it is unclear that the risk for CV thrombotic events is similar for all NSAIDs. The relative increase in serious CV thrombotic events over baseline conferred by NSAID use appears to be similar in those with and without known CV disease or risk factors for CV disease.

Observational studies conducted in the Danish National Registry have demonstrated that patients treated with NSAIDs in the post-MI period were at increased risk of reinfarction, CV-related death, and all-cause mortality beginning in the first week of treatment. Avoid the use of CATAFLAM in patients with a recent MI unless the benefits are expected to outweigh the risk of recurrent CV thrombotic events. If CATAFLAM is used in patients with a recent MI, monitor patients for signs of cardiac ischemia.

Postmarketing surveillance has reported cases of severe hepatic reactions, including liver necrosis, jaundice, fulminant hepatitis with and without jaundice, and liver failure. Some of these reported cases  resulted in fatalities or liver transplantation.

Long-term administration of NSAIDs has resulted in renal papillary necrosis and other renal injury.

NSAIDs, including CATAFLAM can lead to new onset of hypertension or worsening of preexisting hypertension, either of which may contribute to the increased incidence of CV events. Patients taking angiotensin converting enzyme (ACE) inhibitors, thiazides diuretics or loop diuretics may have impaired response to these therapies when taking NSAIDs. Monitor blood pressure (BP) during the initiation of NSAID treatment and throughout the course of therapy.

Increases in serum potassium concentration, including hyperkalemia, have been reported with use of NSAIDs, even in some patients without renal impairment. In patients with normal renal function, these effects have been attributed to a hyporeninemic-hypoaldosteronism state.

Diclofenac has been associated with anaphylactic reactions in patients with and without known hypersensitivity to diclofenac and in patients with aspirin-sensitive asthma.NSAIDs, including diclofenac, can cause serious skin adverse events such as exfoliative dermatitis.

Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal. These serious events may occur without warning. Inform patients about the signs and symptoms of serious skin reactions and discontinue the use of CATAFLAM at the first appearance of skin rash or any other sign of hypersensitivity. CATAFLAM is contraindicated in patients with previous serious skin reactions to NSAIDs.

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) has been reported in patients taking NSAIDs, such as CATAFLAM. Some of these events have been fatal or life-threatening.

Anemia has occurred in NSAID-treated patients. This may be due to occult or gross blood loss, fluid retention, or an incompletely described effect upon erythropoiesis.

Elderly patients, compared to younger patients, are at greater risk for NSAID-associated serious cardiovascular, gastrointestinal, and/or renal adverse reactions. If the anticipated benefit for the elderly patient outweighs these potential risks, start dosing at the low end of the dosing range, and monitor patients for adverse effects.

NSAIDs, including CATAFLAM, may increase the risk of bleeding events. Co-morbid conditions such as coagulation disorders, concomitant use of warfarin and other anticoagulants, antiplatelet agents (e.g., aspirin), serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) may increase this risk. Monitor these patients for signs of bleeding.

Controlled clinical studies showed that the concomitant use of NSAIDs and analgesic doses of aspirin does not produce any greater therapeutic effect than the use of NSAIDs alone. In a clinical study, the concomitant use of an NSAID and aspirin was associated with a significantly increased incidence of GI adverse reactions as compared to use of the NSAID alone. Concomitant use of CATAFLAM and analgesic doses of aspirin is not generally recommended because of the increased risk of bleeding.

During concomitant use of CATAFLAM and ACE-inhibitors, ARBs, or beta-blockers, monitor blood pressure to ensure that the desired blood pressure is obtained. During concomitant use of CATAFLAM and ACE-inhibitors or ARBs in patients who are elderly, volume-depleted, or have impaired renal function, monitor for signs of worsening renal function. When these drugs are administered concomitantly, patients should be adequately hydrated. Assess renal function at the beginning of the concomitant treatment and periodically thereafter.

During concomitant use of CATAFLAM with diuretics, observe patients for signs of worsening renal function, in addition to assuring diuretic efficacy including antihypertensive effects.

The concomitant use of diclofenac with digoxin has been reported to increase the serum concentration and prolong the half-life of digoxin. During concomitant use of CATAFLAM and digoxin, monitor serum digoxin levels.

During concomitant use of CATAFLAM and lithium, monitor patients for signs of lithium toxicity.

Concomitant use of NSAIDs and methotrexate may increase the risk for methotrexate toxicity (e.g., neutropenia, thrombocytopenia, renal dysfunction). During concomitant use of CATAFLAM and methotrexate, monitor patients for methotrexate toxicity.

Concomitant use of CATAFLAM and cyclosporine may increase cyclosporine nephrotoxicity. During concomitant use of CATAFLAM and cyclosporine, monitor patients for signs of worsening renal function.

Concomitant use of diclofenac with other NSAIDs or salicylates (e.g., diflunisal, salsalate) increases the risk of GI toxicity, with little or no increase in efficacy. The concomitant use of diclofenac with other NSAIDs or salicylates is not recommended.

Concomitant use of CATAFLAM and pemetrexed may increase the risk of pemetrexed-associated myelosuppression, renal, and GI toxicity (see the pemetrexed prescribing information). During concomitant use of CATAFLAM and pemetrexed, in patients with renal impairment whose creatinine clearance ranges from 45 to 79 mL/min, monitor for myelosuppression, renal and GI toxicity. NSAIDs with short elimination half-lives (e.g., diclofenac, indomethacin) should be avoided for a period of two days before, the day of, and two days following administration of pemetrexed. In the absence of data regarding potential interaction between pemetrexed and NSAIDs with longer half-lives (e.g., meloxicam, nabumetone), patients taking these NSAIDs should interrupt dosing for at least five days before, the day of, and two days following pemetrexed administration.

Diclofenac is metabolized by cytochrome P450 enzymes, predominantly by CYP2C9. Co-administration of diclofenac with CYP2C9 inhibitors (e.g. voriconazole) may enhance the exposure and toxicity of diclofenac whereas coadministration with CYP2C9 inducers (e.g. rifampin) may lead to compromised efficacy of diclofenac.

Based on the mechanism of action, the use of prostaglandin-mediated NSAIDs, including CATAFLAM, may delay or prevent rupture of ovarian follicles, which has been associated with reversible infertility in some women. Published animal studies have shown that administration of prostaglandin synthesis inhibitors has the potential to disrupt prostaglandin-mediated follicular rupture required for ovulation. Small studies in women treated with NSAIDs have also shown a reversible delay in ovulation. Consider withdrawal of NSAIDs, including CATAFLAM, in women who have difficulties conceiving or who are undergoing investigation of infertility.

Inform pregnant women to avoid use of CATAFLAM and other NSAIDs, starting at 30 weeks gestation
because of the risk of the premature closure of the fetal ductus arteriosus. If treatment with CATAFLAM is
needed for a pregnant woman between about 20 to 30 weeks gestation, advise her that she may need to be monitored for oligohydramnios, if treatment continues for longer than 48 hours.

Based on available data, diclofenac may be present in human milk.

GoToSource

• Use in patients under the age of 18. GoToSource

• Migraine. GoToSource

• E. coli urinary tract infections. GoToSource

Gastrointestinal bleeding, peripheral edema (swelling), hypersensitivity reactions, liver damage and failure. GoToSource

Ischaemic stroke, heart failure, atrial fibrillation (irregular, rapid heart rate), myocardial infarction and cardiac death. GoToSource

Gastrointestinal strictures, perforations, ulceration and perforation. GoToSource

Hypersensitivity reactions. GoToSource

Aplastic anemia (failure of bone marrow to produce blood cells). GoToSource

Hypertension (high blood pressure). GoToSource

Hyponatremia (low blood sodium level) and hyperkalemia (high blood potassium level). GoToSource

Stevens-johnson syndrome and toxic epidermal necrolysis (severe skin disorder). GoToSource

Kounis syndrome. GoToSource

Kidney failure. GoToSource

Lawsuits filed for birth defects, heart attacks and strokes.