Fenoprofen Calcium

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 a nonsteroidal anti-inflammatory drug may cause a dose-dependent reduction in prostaglandin formation and, secondarily, in renal blood flow, which may precipitate overt renal decomposition. Patients at greatest risk of this reaction are those with impaired renal function, heart failure, liver dysfunction, those taking diuretics and ACE inhibitors 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 in patients with advanced renal disease. Therefore, treatment with fenoprofen is not recommended in patients with advanced renal disease (see CONTRAINDICATIONS).

As with other NSAIDs, anaphylactoid reactions may occur in patients without known prior exposure to fenoprofen. Fenoprofen should not be given to patients with the aspirin triad. This symptom complex typically occurs in asthmatic patients who experience rhinitis with or without nasal polyps, or who exhibit severe, potentially fatal bronchospasm after taking aspirin or other NSAIDs (see CONTRAINDICATIONS and PRECAUTIONS: Preexisting Asthma). Emergency help should be sought in cases where an anaphylactoid reaction occurs.

NSAIDs, including fenoprofen, 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. Patients should be informed about the signs and symptoms of serious skin manifestations and use of the drug should be discontinued at the first appearance of skin rash or any other sign of hypersensitivity.

Starting at 30 weeks gestation, fenoprofen and other NSAIDs should be avoided by pregnant women as premature closure of the ductus arteriosus in the fetus may occur.

Studies to date have not shown changes in the eyes attributable to the administration of fenoprofen. 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.

Caution should be exercised by patients whose activities require alertness if they experience CNS side effects while taking fenoprofen.

Since the safety of fenoprofen has not been established in patients with impaired hearing, these patients should have periodic tests of auditory function during prolonged therapy with fenoprofen.

Fenoprofen cannot be expected to substitute for corticosteroids or to treat corticosteroid insufficiency. Abrupt discontinuation of corticosteroids may lead to disease exacerbation. Patients on prolonged corticosteroid therapy should have their therapy tapered slowly if a decision is made to discontinue corticosteroids.

The pharmacological activity of fenoprofen in reducing inflammation may diminish the utility of these diagnostic signs in detecting complications of presumed noninfectious, painful conditions.

Borderline elevations of one or more liver tests may occur in up to 15% of patients taking NSAIDs including fenoprofen. These laboratory abnormalities may progress, may remain unchanged or may be transient with continuing therapy. Notable elevations of ALT or AST (approximately three or more times the upper limit of normal) have been reported in approximately 1% of patients in clinical trials with NSAIDs. In addition, rare cases of severe hepatic reactions, including jaundice and fatal fulminant hepatitis, liver necrosis and hepatic failure, some of them with fatal outcomes have been reported.

A patient with symptoms and/or signs suggesting liver dysfunction, or in whom an abnormal liver test has occurred, should be evaluated for evidence of the development of a more severe hepatic reaction while on therapy with fenoprofen. If clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations occur (e.g., eosinophilia, rash, etc.), fenoprofen should be discontinued.

Anemia is sometimes seen in patients receiving NSAIDs, including fenoprofen. This may be due to fluid retention, occult or gross GI blood loss or an incompletely described effect upon erythropoiesis. Patients on long-term treatment with NSAIDs, including fenoprofen, should have their hemoglobin or hematocrit checked if they exhibit any signs or symptoms of anemia. NSAIDs inhibit platelet aggregation and have been shown to prolong bleeding time in some patients. Unlike aspirin, their effect on platelet function is quantitatively less, of shorter duration, and reversible. Patients receiving fenoprofen who may be adversely affected by alterations in platelet function, such as those with coagulation disorders or patients receiving anticoagulants, should be carefully monitored.

Patients with asthma may have aspirin-sensitive asthma. The use of aspirin in patients with aspirin-sensitive asthma has been associated with severe bronchospasm which can be fatal. Since cross-reactivity, including bronchospasm, between aspirin and other nonsteroidal anti-inflammatory drugs has been reported in such aspirin-sensitive patients, fenoprofen should not be administered to patients with this form of aspirin sensitivity and should be used with caution in patients with preexisting asthma.

Patients should be informed of the following information before initiating therapy with an NSAID and periodically during the course of ongoing therapy. Patients should also be encouraged to read the NSAID Medication Guide that accompanies each prescription dispensed.

1. 1.Cardiovascular Thrombotic Events: Advise patients to be alert for the symptoms of cardiovascular thrombotic events, including chest pain, shortness of breath, weakness, or slurring of speech, and to report any of these symptoms to their healthcare provider immediately (see WARNINGS).
2. 2.Fenoprofen, like other NSAIDs, can cause GI discomfort and, rarely, serious GI side effects, such as ulcers and bleeding, which may result in hospitalization and even death. 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 including epigastric pain, dyspepsia, melena and hematemesis. Patients should be apprised of the importance of this follow-up (see WARNINGS: Gastrointestinal Effects: Risk of Ulceration, Bleeding, and Perforation).
3. 3.Fenoprofen, like other NSAIDs, can cause serious skin side effects such as exfoliative dermatitis, SJS and TEN, which may result in hospitalization and even death. Although serious skin reactions may occur without warning, patients should be alert for the signs and symptoms of skin rash and blisters, fever or other signs of hypersensitivity such as itching, and should ask for medical advice when observing any indicative signs or symptoms. Patients should be advised to stop the drug immediately if they develop any type of rash and contact their physicians as soon as possible.
4. 4.Heart Failure and Edema:Advise patients to be alert for the symptoms of congestive heart failure including shortness of breath, unexplained weight gain, or edema and to contact their healthcare provider if such symptoms occur (see WARNINGS).
5. 5.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.
6. 6.Patients should be informed of the signs of an anaphylactoid reaction (e.g. difficulty breathing, swelling of the face or throat). If these occur, patients should be instructed to seek immediate emergency help (see WARNINGS).
7. 7.Starting at 30 weeks gestation, fenoprofen and other NSAIDs should be avoided by pregnant women as premature closure of the ductus arteriosus in the fetus may occur.

Because serious GI tract ulcerations and bleeding can occur without warning symptoms, physicians should monitor for signs or symptoms of GI bleeding. Patients on long-term treatment with NSAIDs, should have their CBC and a chemistry profile 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, fenoprofen should be discontinued.

In vitro studies have shown that fenoprofen, because of its affinity for albumin, may displace from their binding sites other drugs that are also albumin bound, and this may lead to drug interactions. Theoretically, fenoprofen could likewise be displaced. Patients receiving hydantoins, sulfonamides or sulfonylureas should be observed for increased activity of these drugs and, therefore, signs of toxicity from these drugs.

Amerlex-M kit assay values of total and free triiodothyronine in patients receiving fenoprofen have been reported as falsely elevated on the basis of a chemical cross-reaction that directly interferes with the assay. Thyroid-stimulating hormone, total thyroxine and thyrotropin-releasing hormone response are not affected.

Long-term studies in animals have not been conducted to evaluate the carcinogenic potential of fenoprofen. Studies have not been conducted to determine the effect of fenoprofen on mutagenicity or fertility.

The effects of fenoprofen on labor and delivery in pregnant women are unknown. In rat studies, maternal exposure to NSAIDs, as with other drugs known to inhibit prostaglandin synthesis, increased the incidence of dystocia, delayed parturition and decreased pup survival.

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 fenoprofen, 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 below the age of 18 have not been established.

As with any NSAIDs, caution should be exercised in treating the elderly (65 years and older).

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 as compared to 16.9% of patients receiving placebo. In descending order of frequency, these reactions included dyspepsia (10.3% fenoprofen 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 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 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 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 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% 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).

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 (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.

Symptoms of overdose appear within several hours and generally involve the gastrointestinal and central nervous systems. They include dyspepsia, nausea, vomiting, abdominal pain, dizziness, headache, ataxia, tinnitus, tremor, drowsiness and confusion. Hyperpyrexia, tachycardia, hypotension and acute renal failure may occur rarely following overdose. Respiratory depression and metabolic acidosis have also been reported following overdose with certain NSAIDs.

To obtain up-to-date information about the treatment of overdose, a good resource is your certified Regional Poison Control Center. Telephone numbers of certified poison control centers are listed in the Physicians' Desk Reference (PDR). In managing overdosage, consider the possibility of multiple drug overdoses, interaction among drugs and unusual drug kinetics in your patient.

Protect the patient's airway and support ventilation and perfusion. Meticulously monitor and maintain, within acceptable limits, the patient's vital signs, blood gases, serum electrolytes, etc. Absorption of drugs from the gastrointestinal tract may be decreased by giving activated charcoal, which, in many cases, is more effective than lavage; consider charcoal instead of or in addition to gastric emptying. Repeated doses of charcoal over time may hasten elimination of some drugs that have been absorbed. Safeguard the patient's airway when employing gastric emptying or charcoal.

Alkalinization of the urine, forced diuresis, peritoneal dialysis, hemodialysis and charcoal hemoperfusion do not enhance systemic drug elimination.

For the treatment of mild to moderate pain, the recommended dosage is 200 mg given orally every 4 to 6 hours, as needed.

For the relief of signs and symptoms of rheumatoid arthritis or osteoarthritis the recommended dose is 400 mg to 600 mg given orally, 3 or 4 times a day. The dose should be tailored to the needs of the patient and may be increased or decreased depending on the severity of the symptoms. Dosage adjustments may be made after initiation of drug therapy or during exacerbations of the disease. Total daily dosage should not exceed 3200 mg.

Fenoprofen calcium tablets may be administered with meals or with milk. Although the total amount absorbed is not affected, peak blood levels are delayed and diminished.

Patients with rheumatoid arthritis generally seem to require larger doses of fenoprofen calcium tablets than do those with osteoarthritis. The smallest dose that yields acceptable control should be employed.

Although improvement may be seen in a few days in many patients, an additional 2 to 3 weeks may be required to gauge the full benefits of therapy.