NSAIDs, including FENOPROFEN CALCIUM, USP, can lead to new onset of hypertension or worsening of pre-existing hypertension, either of which may contribute to the increased incidence of CV events. Patients taking angiotensin converting enzyme (ACE) inhibitors, thiazide diuretics, or loop diuretics may have impaired response to these therapies when taking NSAIDs [ see Drug Interactions ( 7) ].
Monitor blood pressure (BP) during the initiation of NSAID treatment and throughout the course of therapy.
The Coxib and traditional NSAID Trialists’ Collaboration meta-analysis of randomized controlled trials demonstrated an approximately two-fold increase in hospitalizations for heart failure in COX-2 selective-treated patients and nonselective NSAID-treated patients compared to placebo-treated patients. In a Danish National Registry study of patients with heart failure, NSAID use increased the risk of MI, hospitalization for heart failure, and death.
Additionally, fluid retention and edema have been observed in some patients treated with NSAIDs. Use of fenoprofen may blunt the CV effects of several therapeutic agents used to treat these medical conditions (e.g., diuretics, ACE inhibitors, or angiotensin receptor blockers [ARBs]) [ see Drug Interactions ( 7) ].
Avoid the use of FENOPROFEN CALCIUM, USP in patients with severe heart failure unless the benefits are expected to outweigh the risk of worsening heart failure. If FENOPROFEN CALCIUM, USP is used in patients with severe heart failure, monitor patients for signs of worsening heart failure.
Long-term administration of NSAIDs has resulted in renal papillary necrosis and other renal injury.
Renal toxicity has also been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion. In these patients, administration of an NSAID may cause a dose-dependent reduction in prostaglandin formation and, secondarily, in renal blood flow, which may precipitate overt renal decompensation. Patients at greatest risk of this reaction are those with impaired renal function, dehydration, hypovolemia, heart failure, liver dysfunction, those taking diuretics and ACE inhibitors or ARBs, and the elderly. Discontinuation of NSAID therapy is usually followed by recovery to the pretreatment state.
No information is available from controlled clinical studies regarding the use of FENOPROFEN CALCIUM, USP in patients with advanced renal disease. The renal effects of FENOPROFEN CALCIUM, USP may hasten the progression of renal dysfunction in patients with pre-existing renal disease.
Correct volume status in dehydrated or hypovolemic patients prior to initiating FENOPROFEN CALCIUM, USP. Monitor renal function in patients with renal or hepatic impairment, heart failure, dehydration, or hypovolemia during use of FENOPROFEN CALCIUM, USP [ see Drug Interactions ( 7) ]. Avoid the use of FENOPROFEN CALCIUM, USP in patients with advanced renal disease unless the benefits are expected to outweigh the risk of worsening renal function. If FENOPROFEN CALCIUM, USP is used in patients with advanced renal disease, monitor patients for signs of worsening renal function.
Hyperkalemia 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.
Fenoprofen has been associated with anaphylactic reactions in patients with and without known hypersensitivity to fenoprofen and in patients with aspirin-sensitive asthma [ see Contraindications ( 4) and Warnings and Precautions ( 5.8) ].
Seek emergency help if an anaphylactic reaction occurs.
A subpopulation of patients with asthma may have aspirin-sensitive asthma which may include chronic rhinosinusitis complicated by nasal polyps; severe, potentially fatal bronchospasm; and/or intolerance to aspirin and other NSAIDs. Because cross-reactivity between aspirin and other NSAIDs has been reported in such aspirin-sensitive patients, FENOPROFEN CALCIUM, USP is contraindicated in patients with this form of aspirin sensitivity [ see Contraindications ( 4) ]. When FENOPROFEN CALCIUM, USP is used in patients with preexisting asthma (without known aspirin sensitivity), monitor patients for changes in the signs and symptoms of asthma.
NSAIDs, including fenoprofen, can cause serious skin adverse reactions 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 to discontinue the use of FENOPROFEN CALCIUM, USP at the first appearance of skin rash or any other sign of hypersensitivity.
FENOPROFEN CALCIUM, USP is contraindicated in patients with previous serious skin reactions to NSAIDs [ see Contraindications ( 4) ].
Fenoprofen may cause premature closure of the fetal ductus arteriosus. Avoid use of NSAIDs, including FENOPROFEN CALCIUM, USP, in pregnant women starting at 30 weeks of gestation (third trimester) [ see Use in Specific Populations ( 8.1) ].
Anemia has occurred in NSAID-treated patients. This may be due to occult or gross blood loss, fluid retention, or an incompletely described effect on erythropoiesis. If a patient treated with FENOPROFEN CALCIUM, USP has any signs or symptoms of anemia, monitor hemoglobin or hematocrit.
NSAIDs, including FENOPROFEN CALCIUM, USP, may increase the risk of bleeding events. Co-morbid conditions such as coagulation disorders, concomitant use of warfarin, 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 [ see Drug Interactions ( 7) ].
The pharmacological activity of FENOPROFEN CALCIUM, USP in reducing inflammation, and possibly fever, may diminish the utility of diagnostic signs in detecting infections.
Because serious GI bleeding, hepatotoxicity, and renal injury can occur without warning symptoms or signs, consider monitoring patients on long-term NSAID treatment with a CBC and a chemistry profile periodically [ see Warnings and Precautions ( 5.2, 5.3, 5.6) ].
Studies to date have not shown changes in the eyes attributable to the administration of FENOPROFEN CALCIUM, USP. However, adverse ocular effects have been observed with other anti-inflammatory drugs. Eye examinations, therefore, should be performed if visual disturbances occur in patients taking FENOPROFEN CALCIUM, USP.
Caution should be exercised by patients whose activities require alertness if they experience CNS side effects while taking FENOPROFEN CALCIUM, USP.
Since the safety of FENOPROFEN CALCIUM, USP has not been established in patients with impaired hearing, these patients should have periodic tests of auditory function during prolonged therapy with FENOPROFEN CALCIUM, USP.
The following adverse reactions are discussed in greater detail in other sections of the labeling:
- Cardiovascular Thrombotic Events [ see Warnings and Precautions ( 5.1) ]
- GI Bleeding, Ulceration and Perforation [ see Warnings and Precautions ( 5.2) ]
- Hepatotoxicity [ see Warnings and Precautions ( 5.3) ]
- Hypertension [ see Warnings and Precautions ( 5.4) ]
- Heart Failure and Edema [ see Warnings and Precautions ( 5.5) ]
- Renal Toxicity and Hyperkalemia [ see Warnings and Precautions ( 5.6) ]
- Anaphylactic Reactions [ see Warnings and Precautions ( 5.7) ]
- Serious Skin Reactions [ see Warnings and Precautions ( 5.9) ]
- Hematologic Toxicity [ see Warnings and Precautions ( 5.11) ]
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
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, USP, the most common adverse reactions were gastrointestinal in nature and occurred in 20.8% of patients receiving FENOPROFEN CALCIUM, USP as compared to 16.9% of patients receiving placebo. In descending order of frequency, these reactions included dyspepsia (10.3% FENOPROFEN CALCIUM, USP 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, USP 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, USP 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, USP 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, USP 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, gastrointestinal hemorrhage, anorexia, flatulence, dry mouth, and blood in the stool. Increases in alkaline phosphatase, LDH, SGOT, jaundice, and cholestatic hepatitis, aphthous ulcerations of the buccal mucosa, metallic taste, and pancreatitis.
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.
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.
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