Nalfon (Fenoprofen Calcium)

NALFON®

Lilly

Fenoprofen Calcium

Anti-inflammatory – Analgesic

Action And Clinical Pharmacology: Fenoprofen has demonstrated anti-inflammatory, analgesic and antipyretic activities in animal studies. Although fenoprofen’s modes of action are unknown, in vitro tests have shown that it inhibits synthesis and/or release of prostaglandins; stabilizes lysosomes; inhibits platelet aggregation and platelet adhesiveness, and enhances fibrinolytic activity. All of these activities may have a role in the amelioration of inflammation, pain and fever. Animal studies indicate that fenoprofen does not stimulate the pituitary or adrenal glands; therefore, its effects are not mediated by secretions from these glands. In clinical trials 2.4 g of fenoprofen produced approximately the same clinical activity as 3.9 g of ASA.

Under fasting conditions, fenoprofen is rapidly absorbed, and peak plasma levels of 50 µg/L are achieved within 2 hours after oral administration of 600 mg doses. Good dose proportionality was observed between 200 and 600 mg doses in fasting male volunteers. The plasma half-life is approximately 3 hours. About 90% of a single oral dose is eliminated within 24 hours as fenoprofen glucuronide and 4¢-hydroxyfenoprofen glucuronide, the major urinary metabolites of fenoprofen. Fenoprofen is highly bound (99%) to albumin. Peak plasma levels of fenoprofen in normal elderly volunteers were similar to those observed in normal young volunteers. Elderly volunteers had a mean plasma clearance of 2.2 L/hour while plasma clearance of fenoprofen in normal young volunteers ranged from 3 to 3.5 L/hour. The overall elimination rate constant, plasma half-life and ratio of renal to nonrenal clearance of fenoprofen was the same in elderly and young volunteers. The 30 to 60% decrease in plasma clearance is due to a decrease in the volume of distribution in the body. The concomitant administration of antacid (containing both aluminum and magnesium hydroxide) does not interfere with absorption of fenoprofen. There is less suppression of collagen-induced platelet aggregation with single doses of fenoprofen than there is with ASA.

Indications And Clinical Uses: Treatment of rheumatoid arthritis and osteoarthritis.

Contra-Indications: Peptic ulcer or any inflammatory gastrointestinal tract disease. Hypersensitivity to fenoprofen.

Fenoprofen should not be used in patients in whom acute asthmatic attacks, urticaria, rhinitis or other allergic manifestations are precipitated by ASA or other nonsteroidal anti-inflammatory agents. Fatal anaphylactoid reactions have occurred in such individuals. Fenoprofen should not be administered to patients with a history of significantly impaired renal function.

Data to establish safety and a dosage regimen in the pediatric age group are not available at this time, and use in children under 14 years of age is contraindicated.

Manufacturers’ Warnings In Clinical States: Peptic ulceration, perforation and gastrointestinal bleeding, sometimes severe and occasionally fatal have been reported during therapy with nonsteroidal anti-inflammatory drugs (NSAIDs) including fenoprofen. Fenoprofen should be given under close medical supervision to patients prone to gastrointestinal tract irritation particularly those with a history of peptic ulcer, diverticulosis or other inflammatory disease of the gastrointestinal tract. Patients taking any NSAID including fenoprofen should be instructed to contact a physician immediately if they experience symptoms or signs suggestive of peptic ulceration or gastrointestinal bleeding. These reactions can occur without warning symptoms or signs and at any time during treatment. Elderly, frail and debilitated patients appear to be at higher risk from a variety of adverse reactions from NSAIDs. For such patients, consideration should be given to a starting dose lower than usual, with individual adjustments when necessary and under close supervision. Since fenoprofen has been marketed, there have been reports of genitourinary tract problems in patients taking it. The most frequent reported problems have been episodes of dysuria, cystitis, hematuria, interstitial nephritis, and nephrotic syndrome. This syndrome may be preceded by the appearance of fever, rash, arthralgia, oliguria, and azotemia and may progress to anuria. There may also be substantial proteinuria, and, on renal biopsy, electron microscopy has shown foot process fusion and T-lymphocyte infiltration in the renal interstitium. Early recognition of the syndrome and withdrawal of the drug have been followed by rapid recovery. Administration of steroids and the use of dialysis have also been included in the treatment. Because a syndrome with some of these characteristics has also been reported with other NSAIDs, it is recommended that patients who have had these reactions with other such drugs not be treated with fenoprofen. In patients with possibly compromised renal function, periodic renal function examinations should be done.

Precautions: Gastrointestinal: If peptic ulceration is suspected or confirmed, or if gastrointestinal bleeding or perforation occurs fenoprofen should be discontinued, an appropriate treatment instituted and patient closely monitored. There is no definitive evidence that the concomitant administration of histamine H2-receptor antagonists and/or antacids will either prevent the occurrence of gastrointestinal side effects or allow continuation of fenoprofen calcium therapy when and if these adverse reactions appear.

Renal: As with nonsteroidal anti-inflammatory drugs, long-term administration of fenoprofen to animals has resulted in renal papillary necrosis and other abnormal renal pathology. In humans, there have been reports of acute interstitial nephritis with hematuria, proteinuria and occasionally nephrotic syndrome. A second form of renal toxicity has been seen in patients with prerenal conditions leading to the reduction in renal blood flow or blood volume, where the renal prostaglandins have a supportive 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 may precipitate overt renal decompensation. Patients at greatest risk of this reaction are those with impaired renal function, heart failure, liver dysfunction, those taking diuretics, and the elderly. Discontinuation of nonsteroidal anti-inflammatory therapy is usually followed by recovery to the pretreatment state. Fenoprofen and its metabolites are eliminated primarily by the kidneys, therefore the drug should be used with great caution in patients with impaired renal function, especially the elderly. In these cases, lower doses of fenoprofen should be anticipated and patients carefully monitored. During long-term therapy, kidney function should be monitored periodically.

Hepatic: As with other nonsteroidal anti-inflammatory drugs, borderline elevations in 1 or more liver tests may occur. These abnormalities may progress, may remain essentially unchanged, or may be transient with continued therapy. 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 more severe hepatic reactions while on therapy with this drug. Severe hepatic reactions, including jaundice and cases of fatal hepatitis, have been reported with this drug, as with other nonsteroidal anti-inflammatory drugs. Although such reactions are rare, if abnormal liver tests persist or worsen, if clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations occur (e.g., eosinophilia and rash), this drug should be discontinued. During long-term therapy, liver function should be monitored periodically. If this drug is to be used in the presence of impaired liver function, it must be done under strict supervision.

Fluid and Electrolyte Balance: Fluid retention and edema have been observed in patients treated with fenoprofen. Therefore, as with many other nonsteroidal anti-inflammatory drugs, the possibility of precipitating congestive heart failure in elderly patients or those with compromised cardiac function should be borne in mind. Fenoprofen should be used with caution in patients with heart failure, hypertension or other conditions predisposing to fluid retention. Serum electrolytes should be monitored periodically during long-term therapy, especially in those patients at risk.

Hematology: Drugs inhibiting prostaglandin biosynthesis do interfere with platelet function to some degree; therefore, patients who may be adversely affected by such an action should be carefully observed when fenoprofen is administered. Blood dyscrasias associated with the use of nonsteroidal anti-inflammatory drugs are rare, but could be with severe consequences.

Infection: In common with other anti-inflammatory drugs, fenoprofen may mask the usual signs of infection.

Ophthalmology: Blurred and/or diminished vision has been reported with the use of fenoprofen and other nonsteroidal anti-inflammatory drugs. If such symptoms develop, this drug should be discontinued and an ophthalmologic examination performed; ophthalmic examination should be carried out at periodic intervals in any patient receiving this drug for an extended period of time.

CNS: Caution should be exercised by patients whose activities require alertness if they experience CNS side effects while taking fenoprofen. Peripheral edema has been observed in some patients taking fenoprofen; therefore, fenoprofen should be used with caution in patients with compromised cardiac function or hypertension. The possibility of renal involvement should be considered.

Pregnancy: Fenoprofen’s safety in human pregnancy has not been established. Therefore, it should be used in pregnancy only when possible benefits to the patient outweigh possible risks to the fetus. Animal reproductive studies with fenoprofen have not revealed teratogenic or embryocidal effects. Animal experiments indicate that the drug interferes with parturition and therefore its use during labor is not recommended.

Drug Interactions: The coadministration of ASA decreases the biologic half-life of fenoprofen because of an increase in metabolic clearance that results in a greater amount of hydroxylated fenoprofen in the urine. Although the mechanism of interaction between fenoprofen and ASA is not totally known, enzyme induction and displacement of fenoprofen from plasma albumin binding sites are possibilities. Because fenoprofen has not been shown to produce any additional effect beyond that obtained with ASA alone and because ASA increases the rate of excretion of fenoprofen, the concomitant use of fenoprofen and salicylates is not recommended. Chronic administration of phenobarbital, a known enzyme inducer, may be associated with a decrease in the plasma half-life of fenoprofen. When phenobarbital is added to or withdrawn from treatment, dosage adjustment of fenoprofen may be required. 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 interaction. Theoretically, fenoprofen could likewise be displaced. Patients receiving hydantoin, sulfonamides or sulfonylureas should be observed for increased activity of these drugs and, therefore, signs of toxicity from these drugs. In patients receiving coumarin-type anticoagulants, the addition of fenoprofen to therapy could prolong the prothrombin time. Patients receiving both drugs should be under careful observation. Patients treated with fenoprofen may be resistant to the effects of loop diuretics.

Laboratory Test Interactions : Amerlex-M kit assay values of total and free triiodothyronine in patients receiving fenoprofen calcium 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.

Adverse Reactions: The potential for adverse reactions was assessed in 6 786 patients. The most common adverse reactions encountered with NSAIDs are gastrointestinal, of which peptic ulcer, with or without bleeding, is the most severe. Fatalities have occurred on occasion, particularly in the elderly.

Gastrointestinal: During clinical trials with fenoprofen, the most common adverse reactions were gastrointestinal in nature and occurred in about 20.8% of patients. In descending order of frequency, these reactions included dyspepsia (10.3%), nausea (7.7%), constipation (7%), vomiting (2.6%), abdominal pain (2%) and diarrhea (1.8%).

Allergic: 2 instances of hypersensitivity were reported. Angioedema (angioneurotic edema).

CNS: The most frequent adverse neurologic reactions were headache (8.7%) and somnolence (8.5%). Dizziness (6.5%), tremor (2.2%), confusion (1.4%) and insomnia were noted less frequently. Fenoprofen was discontinued in less than 0.5% of patients because of these side effects.

Dermatologic: pruritus (4.2%), rash (3.7%), increased sweating (4.6%) and urticaria were observed. Exfoliative dermatitis, toxic epidermal necrolysis, Stevens-Johnson syndrome and alopecia have also been reported.

Cardiovascular: palpitations (2.5%), atrial fibrillation, pulmonary edema, ECG changes and supraventricular tachycardia.

Special Senses: tinnitus (4.5%), blurred vision (2.2%), and decreased hearing (1.6%). Burning tongue, diplopia and optic neuritis were reported.

Hematologic: purpura, bruising, hemorrhage, thrombocytopenia, hemolytic anemia, aplastic anemia, agranulocytosis and pancytopenia have been reported to occur at a frequency of
Renal: azotemia, interstitial nephritis, nephrosis, papillary necrosis, dysuria, cystitis, hematuria, oliguria and anuria have been observed at a frequency of
Hepatic: jaundice, cholestatic hepatitis, increase in alkaline phosphatase, LDH and AST.

Respiratory: dyspnea (2.8%), upper respiratory infection (1.5%) and nasopharyngitis (1.2%) were reported.

Other: nervousness (5.7%), asthenia (5.4%), fatigue (1.7%) and peripheral edema (5%).

Symptoms And Treatment Of Overdose: Symptoms: 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. tag_Treatment

Treatment: 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 emesis or 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.

Dosage And Administration: Rheumatoid Arthritis: Initiate the treatment of active rheumatoid arthritis with 600 mg 3 or 4 times a day. Once a satisfactory response has been obtained, decrease the daily dose in increments of 300 mg until the minimum effective dose has been established. Doses as low as 600 mg daily have been shown to control mild disease activity in the occasional patient. In the event of inadequate response, increase the dosage in increments of 300 mg. Maximum fenoprofen daily dose should not exceed 3.0 g.

Osteoarthritis: Patients with degenerative joint disease in general require less medication than those with rheumatoid arthritis. Doses of 300 to 600 mg may be given 3 to 4 times a day to alleviate pain and increase mobility. Adjust the dose to the patient’s need. Only infrequently will it be necessary to increase the daily dose to 2.4 g.

Availability And Storage: Each para capsule shaped, scored, yellow film-coated tablet, marked “Lilly” and “NALFON”, contains: fenoprofen calcium equivalent to fenoprofen 600 mg. Tartrazine-free. Nonmedicinal ingredients: cornstarch, dibasic calcium phosphate, magnesium stearate, polacrilin potassium and stearic acid; coating: benzyl alcohol, hydroxypropyl methylcellulose, polyethylene glycol, propylene glycol, titanium dioxide and yellow orange S Aluminum Lake. Bottles of 100.

NALFON® Lilly Fenoprofen Calcium Anti-inflammatory – Analgesic

Connected Diseases :

Arthritis, Rheumatoid

General Illness Information Common Name: ARTHRITIS, RHEUMATOID Medical Term: None Specified Description: A chronic auto-immune disease characterized by inflammation, swelling and pain in the joints,…

Osteoarthritis

General Illness Information Common Name: Osteoarthritis Medical Term: (Degenerative Arthritis) Description: Osteoarthritis is a type of arthritis caused by inflammation, breakdown and eventual loss of…