FDA label 60cd848f-e474-0c14-e053-2991aa0aa99a

Cardiovascular Risk Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) may cause an increased risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which can be fatal. This risk may increase with duration of use. Patients with cardiovascular disease or risk factors for cardiovascular disease may be at greater risk (see WARNINGS ). Fenoprofen Calcium is contraindicated for the treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery (see WARNINGS ). Gastrointestinal Risk NSAIDs cause an increased risk of serious gastrointestinal adverse events including bleeding, ulceration, and perforation of stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Elderly patients are at greater risk for serious gastrointestinal events (see WARNINGS ).

Serious side effects include: heart attack stroke high blood pressure heart failure from body swelling (fluid retention) kidney problems including kidney failure bleeding and ulcers in the stomach and intestine low red blood cells (anemia) life-threatening skin reactions life-threatening allergic reactions liver problems including liver failure asthma attacks in people who have asthma Other side effects include: stomach pain constipation diarrhea gas heartburn nausea vomiting dizziness

WARNINGS CARDIOVASCULAR EFFECTS Cardiovascular Thrombotic Events 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, myocardial infarction, and stroke, which can be fatal. All NSAIDs, both COX-2 selective and nonselective, may give a similar risk. Patients with known CV disease or risk factors for CV disease may be at greater risk. To minimize the potential risk for an adverse CV event in patients treated with an NSAID, the lowest effective dose should be used for the shortest duration possible. Physicians and patients should remain alert for the development of such events, even in the absence of previous CV symptoms. Patients should be informed about the signs and/or symptoms of serious CV events and the steps to take if they occur. There is no consistent evidence that concurrent use of aspirin mitigates the increased risk of serious CV thrombotic events associated with NSAID use. The concurrent use of aspirin and an NSAID does increase the risk of serious GI events (see WARNINGS - Gastrointestinal Effects ). Two large, controlled, clinical trials of a COX-2 selective NSAID for the treatment of pain in the first 10-14 days following CABG surgery found an increased incidence of myocardial infarction and stroke (see CONTRAINDICATIONS ). Hypertension NSAIDs, including Fenoprofen Calcium, can lead to onset of new hypertension or worsening of pre-existing hypertension, either of which may contribute to the increased incidence of CV events. Patients taking thiazides or loop diuretics may have impaired response to these therapies when taking NSAIDs. NSAIDs, including Fenoprofen Calcium, should be used with caution in patients with hypertension. Blood pressure should be monitored closely during the initiation of NSAID treatment and throughout the course of therapy. Congestive Heart Failure and Edema Fluid retention and edema have been observed in some patients taking NSAIDs. Fenoprofen Calcium should be used with caution in patients with fluid retention, compromised cardiac function or heart failure. The possibility of renal involvement should be considered.

ADVERSE REACTIONS During clinical studies for rheumatoid arthritis, osteoarthritis, or mild to moderate pain and studies of pharmacokinetics, complaints were compiled from a checklist of potential adverse reactions, and the following data emerged. These encompass observations in 6,786 patients, including 188 observed for at least 52 weeks. For comparison, data are also presented from complaints received from the 266 patients who received placebo in these same trials. During short-term studies for analgesia, the incidence of adverse reactions was markedly lower than that seen in longer-term studies. Adverse Drug Reactions Reported in > 1% of Patients During Clinical Trials Digestive System —During clinical trials with Fenoprofen Calcium, the most common adverse reactions were gastrointestinal in nature and occurred in 20.8% of patients receiving Fenoprofen Calcium as compared to 16.9% of patients receiving placebo. In descending order of frequency, these reactions included dyspepsia (10.3% Fenoprofen Calcium vs. 2.3% placebo), nausea (7.7% vs. 7.1%), constipation (7% vs. 1.5%), vomiting (2.6% vs. 1.9%), abdominal pain (2% vs. 1.1%), and diarrhea (1.8% vs. 4.1%). The drug was discontinued because of adverse gastrointestinal reactions in less than 2% of patients during premarketing studies. Nervous System —The most frequent adverse neurologic reactions were headache (8.7% vs. 7.5%) and somnolence (8.5% vs. 6.4%). Dizziness (6.5% vs. 5.6%), tremor (2.2% vs. 0.4%), and confusion (1.4% vs. none) were noted less frequently. Fenoprofen Calcium was discontinued in less than 0.5% of patients because of these side effects during premarketing studies. Skin and Appendages — Increased sweating (4.6% vs. 0.4%), pruritus (4.2% vs. 0.8%), and rash (3.7% vs. 0.4%) were reported. Fenoprofen Calcium was discontinued in about 1% of patients because of an adverse effect related to the skin during premarketing studies. Special Senses —Tinnitus (4.5% vs. 0.4%), blurred vision (2.2% vs. none), and decreased hearing (1.6% vs. none) were reported. Fenoprofen Calcium was discontinued in less than 0.5% of patients because of adverse effects related to the special senses during premarketing studies. Cardiovascular —Palpitations (2.5% vs. 0.4%). Fenoprofen Calcium was discontinued in about 0.5% of patients because of adverse cardiovascular reactions during premarketing studies. Miscellaneous —Nervousness (5.7% vs. 1.5%), asthenia (5.4% vs. 0.4%), peripheral edema (5.0% vs. 0.4%), dyspnea (2.8% vs. none), fatigue (1.7% vs. 1.5%), upper respiratory infection (1.5% vs. 5.6%), and nasopharyngitis (1.2% vs. none). Adverse Drug Reactions Reported in <1% of Patients During Clinical Trials Digestive System —Gastritis, peptic ulcer with/without perforation, gastro- intestinal hemorrhage, anorexia, flatulence, dry mouth, blood in the stool. Increases in alkaline phosphatase, LDH, SGOT, jaundice, cholestatic hepatitis, aphthous ulcerations of the buccal mucosa, metallic taste, and pancreatitis (see PRECAUTIONS ). Cardiovascular —Atrial fibrillation, pulmonary edema, electrocardiographic changes, and supraventricular tachycardia. Genitourinary Tract —Renal failure, dysuria, cystitis, hematuria, oliguria, azotemia, anuria, interstitial nephritis, nephrosis, and papillary necrosis (see WARNINGS ). Hypersensitivity —Angioedema (angioneurotic edema). Hematologic —Purpura, bruising, hemorrhage, thrombocytopenia, hemolytic anemia, aplastic anemia, agranulocytosis, and pancytopenia. Nervous System —Depression, disorientation, seizures, and trigeminal neuralgia. Special Senses —Burning tongue, diplopia, and optic neuritis. Skin and Appendages —Exfoliative dermatitis, toxic epidermal necrolysis, Stevens-Johnson syndrome, and alopecia. Miscellaneous —Anaphylaxis, urticaria, malaise, insomnia, tachycardia, personality change, lymphadenopathy, mastodynia, and fever.