Ansaid 100 mg

Concomitant administration of NSAIDs and SSRIs may increase the risk of gastrointestinal ulceration and bleeding (see Warnings and Precautions, Gastrointestinal (GI)).

Concomitant administration of flurbiprofen and hypoglycemic agents revealed a slight reduction in blood sugar concentrations but no signs or symptoms of hypoglycemia.

No drug interaction data are available for Ansaid and the co-administration of oral contraceptives.

There is an increased risk of bleeding, via inhibition of platelet function, when anti-platelet agents are combined with NSAIDs, such as Ansaid (see Warnings and Precautions, Hematologic, Anti-platelet Effects).

Ansaid pretreatment attenuated the hypotensive effect of propranolol but did not appear to affect the ß-blocker mediated reduction in heart rate.

Numerous studies have shown that the concomitant use of NSAIDs and oral glucocorticoids increases the risk of GI side effects such as ulceration and bleeding. This is especially the case in older (>65 years of age) individuals.

Combined use of lithium and flurbiprofen resulted in significant elevation of lithium trough plasma concentration and area under the curve. When lithium and flurbiprofen are concurrently administered, a reduction in lithium dose is recommended. Plasma concentrations of lithium should also be monitored when stopping or starting a NSAID.

Numerous studies have shown that the concomitant use of NSAIDs and anticoagulants increases the risk of GI adverse events such as ulceration and bleeding (see Warnings and Precautions, Hematologic, Anti-coagulants).

Because prostaglandins play an important role in hemostasis, and NSAIDs affect platelet function, concurrent therapy of Ansaid with warfarin requires close monitoring to be certain that no change in anticoagulant dosage is necessary.

NSAIDs may diminish the anti-hypertensive effect of Angiotensin Converting Enzyme (ACE) inhibitors.

Combinations of ACE inhibitors, angiotensin-II antagonists, or diuretics with NSAIDs might have an increased risk for acute renal failure and hyperkalemia. Blood pressure and renal function (including electrolytes) should be monitored more closely in this situation, as occasionally there can be a substantial increase in blood pressure.

Concurrent administration with flurbiprofen did not reveal a change in steady state serum levels of either drug.

Factors such as excess alcohol intake, smoking, age, female gender and concomitant NSAID and oral steroid or anticoagulant use have been associated with increased risk of GI adverse events such as ulceration and bleeding.

Ansaid is extensively protein bound (99%) to human serum albumin. Less than 10% of the primary binding sites were estimated to be occupied at therapeutic drug concentrations. In vitro studies suggest that Ansaid binds to a different primary site on albumin (Type II) than drugs such as anticoagulants, sulfonamides and phenytoin (Type I). However, patients with such combination therapy should be monitored.

Interactions with food have not been established.

Interactions with laboratory tests have not been established.

A small but statistically significant increase in flurbiprofen serum concentration may result with administration of these agents.

Although this interaction has not been studied with flurbiprofen, co-administration of cyclosporin or tacrolimus and any NSAID may increase the nephrotoxic effect of cyclosporin or tacrolimus due to the NSAID's effect on renal prostaglandins. Renal function should be monitored when flurbiprofen and either of these drugs are used in combination.

The use of Ansaid in addition to any other NSAID, including over-the-counter ones (such as ASA and ibuprofen) for analgesic and/or anti-inflammatory effects is not recommended because of the absence of any evidence demonstrating synergistic benefits and the potential for additive adverse reactions.

The exception is the use of low dose ASA for cardiovascular protection, when another NSAID is being used for its analgesic/anti-inflammatory effect, keeping in mind that combination NSAID therapy is associated with additive adverse reactions. The concurrent administration of Ansaid and ASA may result in significantly lowering flurbiprofen concentrations.

Some NSAIDs (e.g. ibuprofen) may interfere with the anti-platelet effects of low dose ASA, possibly by competing with ASA for access to the active site of cyclooxygenase-1.

Interactions with herbal products have not been established.

Clinical studies as well as post-marketing observations have shown that NSAIDs can reduce the effect of diuretics.

Ansaid can interfere with the effects of furosemide. NSAIDs have been shown to interfere with the action of thiazide diuretics and potassium-sparing diuretics.

In geriatric subjects, antacid suspensions caused a reduction in the rate but not the extent of flurbiprofen absorption.

Although a pharmacokinetic interaction has not been reported between low dose methotrexate and flurbiprofen, in rheumatoid arthritis patients with normal renal function, monitoring of toxic signs and symptoms and renal function is recommended. The dose of methotrexate should be reduced if toxicity or impairment of renal function is observed. The interaction of intermediate and high dose methotrexate and flurbiprofen has not been studied. Since significant toxicity has been reported with coadministration of intermediate or high dose methotrexate and other NSAIDs, the concomitant use of intermediate or high dose methotrexate and flurbiprofen should be avoided.

Consideration should be given to reducing the starting dose in elderly patients.

The recommended dosage is 50 mg given four times daily.

The recommended dose is 200 mg per day given in divided doses. Some patients may require up to 300 mg per day. The dose should be adjusted until the minimum effective maintenance dose is established. During the course of treatment, the maximum daily dose of 300 mg should be used only during symptom exacerbations and not for maintenance therapy (see Adverse Reactions).

The usual recommended dose is 50 mg given every four to six hours as needed.

Ansaid (flurbiprofen) should be taken immediately after a meal, or with food or milk.

The missed dose should be taken as soon as remembered. If the next dose is due within 2 hours, a single dose should be taken and the next dose skipped.

Incidence 0.1 to 1.0%: increased appetite, stomatitis, gastrointestinal distress, gastritis, gastroenteritis, ulcer (peptic, gastric or duodenal), melena (includes rectal bleed, bloody diarrhea), oral inflammation, eructation, dry mouth, esophagitis, hematemesis, colitis, hepatitis, rectal discomfort, periodontal abscess, gingivitis, glossitis, anorexia, vomiting. Incidence less than 0.1%: gums bleeding, cholecystitis.

Decrease in hemoglobin and hematocrit was observed in clinical trials at an incidence of 4.6 %. Iron deficiency anemia, ecchymosis, eosinophilia, leukopenia, lymphadenopathy, neutropenia were reported in clinical trials at an incidence of 0.1% to 1.0% (see Adverse Reactions, Clinical Trial Adverse Drug Reactions).

Additional reports of serious adverse events temporally associated with Ansaid during worldwide post-marketing experience are included below. Because these events are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or clearly establish a causal relationship to Ansaid exposure. These include the following: Aseptic meningitis, cholestatic and non-cholestatic jaundice, exacerbation of inflammatory bowel disease, small intestine inflammation with loss of blood and protein, photosensitivity, toxic epidermal necrolysis, interstitial nephritis anaphylaxis, Stevens-Johnson syndrome.

Ear: vertigo 0.6%; pain 0.3%; disorder 0.2%. Incidence less than 0.1%: vestibular disturbances.

Eye: ocular inflammations 0.3%; amblyopia 0.6%; vision disturbances 0.4%; blepharitis 0.1%; conjunctivitis 0.5%; keratoconjunctivitis 0.1%; photophobia 0.1%. Incidence less than 0.1%: diplopia, visual field problems, corneal opacity, lacrimal distress, glaucoma, pain, scleritis.

Others: taste changes 0.2%; parosmia <0.1%.

Incidence 0.1 to 1.0%: bronchitis, epistaxis, increase in cough, dyspnea, laryngitis, lung disorder, asthma, voice alterations. Incidence less than 0.1%: hyperventilation, pleural distress, pulmonary infarct, pulmonary embolism, pneumonia.

Incidence 0.1% to 1.0%: fever, abdominal enlargement, chills, infection, allergic reaction, death. Incidence less than 0.1%: injury.

Incidence 0.1 to 1.0%: weight changes, hyperuricemia. Incidence less than 0.1%: electrolyte changes (Ca++, K+), increased CPK, thirst.

Incidence 0.1% to 1.0%: iron deficiency anemia, ecchymosis, eosinophilia, leukopenia, lymphadenopathy, neutropenia. Incidence less than 0.1%: anemia, leukocytosis, petechia, thrombocytopenia, WBC abnormality.

Incidence 0.1 to 1.0%: arthritis, injury, myalgia. Incidence less than 0.1%: myasthenia, tenosynovitis, joint disease.

Incidence 0.1 to 1.0%: urine abnormalities, hematuria, cystitis, frequency, vaginitis, breast pain, kidney function abnormalities. Incidence less than 0.1%: dysuria, albuminuria, pyuria, pain, kidney stones, kidney failure, incontinence, ejaculatory abnormality, leukorrhea, urethritis, retention, dysmenorrhea, menstrual distress, impotence.

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, particularly in the elderly.

Incidence 0.1% to 1.0%: somnolence, hypertonia, insomnia, nervousness, paresthesia, depression, mood changes, tremors, anxiety, amnesia, migraine, ataxia, cerebrovascular accident, confusion, cerebral ischemia, malaise, increased reflex. Incidence less than 0.1%: EEG abnormalities, neuralgia, convulsions, meningitis, speech disorder, twitch, euphoria, decreased libido.

Incidence 0.1 to 1.0%: herpetic infections, alopecia, dry skin, eczema, nail discoloration, pruritus, sweating, skin ulcerations, urticaria. Incidence less than 0.1%: seborrhea, angioedema, exfoliation.

Incidence 0.1 to 1.0%: hypertension, arrhythmias, inotropic problems, palpitations, vasodilatation, angina, phlebitis, vascular distress, extrasystoles, right heart failure, myocardial infarction, vasculitis. Incidence less than 0.1%: tachycardia, syncope.

Safety and efficacy have not been established in the pediatric population (see Contraindications).

Evidence from clinical studies and postmarket experience suggests that use in the geriatric population is associated with differences in safety (see Warnings and Precautions, Special Populations).

Each white, elliptical, film-coated tablet imprinted with Ansaid logo contains: flurbiprofen 50 mg. Nonmedicinal ingredients: carnauba wax, colloidal silicon dioxide, croscarmellose sodium, hypromellose, lactose, magnesium stearate, microcrystalline cellulose, propylene glycol and titanium dioxide. Bottles of 100.

Each blue, elliptical, film-coated tablet imprinted with Ansaid logo contains: flurbiprofen 100 mg. Nonmedicinal ingredients: carnauba wax, colloidal silicon dioxide, croscarmellose sodium, FD&C Blue No. 2, hypromellose, lactose, magnesium stearate, microcrystalline cellulose, propylene glycol and titanium dioxide. Gluten-free. Bottles of 100.

Renal function (serum creatinine, and serum urea, etc.) should be monitored in high-risk populations, such as the elderly, patients with advanced renal disease, patients with cardiovascular disease and diabetes mellitus, as well as in the setting of concomitant use of diuretics, ACE inhibitors, and methotrexate (see Contraindications; Drug Interactions, Anti-hypertensives and Methotrexate; Warnings and Precautions, Fluid and Electrolyte Balance). If abnormal renal tests persist or worsen, Ansaid should be discontinued.

Patients on long term treatment with NSAIDs, including Ansaid, should have their electrolytes such as serum potassium checked regularly if they exhibit any signs or symptoms of renal disease (see Warnings and Precautions, Fluid and Electrolyte Balance).

(See Contraindications, Coronary Artery Bypass Graft Surgery.)

Numerous studies have shown that the concomitant use of NSAIDs and anti-coagulants increases the risk of bleeding. Concurrent therapy of Ansaid with warfarin requires close monitoring of the international normalized ratio (INR).

Even with therapeutic INR monitoring, increased bleeding may occur.

Ansaid (flurbiprofen) is not a substitute for corticosteroids. It does not treat corticosteroid insufficiency. Abrupt discontinuation of corticosteroids may lead to exacerbation of corticosteroid-responsive illness. Patients on prolonged corticosteroid therapy should have their therapy tapered slowly if a decision is made to discontinue corticosteroids (see Drug Interactions, Drug-Drug Interactions, Glucocorticoids).

ASA-induced asthma is an uncommon but very important indication of ASA and NSAID sensitivity. It occurs more frequently in patients with asthma who have nasal polyps.

Blurred and/or diminished vision has been reported with the use of NSAIDs, including Ansaid. If such symptoms develop, Ansaid should be discontinued and an ophthalmologic examination performed. Ophthalmologic examination should be carried out at periodic intervals in any patient receiving Ansaid for an extended period of time.

Ansaid is contraindicated for use during the third trimester of pregnancy because of risk of premature closure of the ductus arteriosus and the potential to prolong parturition.

Caution should be exercised in prescribing Ansaid during the first and second trimesters of pregnancy.

Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or the embryo-fetal development. Data from epidemiological studies suggest an increased risk of miscarriage and of cardiac malformation after use of a prostaglandin synthesis inhibitor in early pregnancy.

In animals, administration of a prostaglandin synthesis inhibitor has been shown to result in increased pre- and post-implantation loss and embryo-fetal lethality. In addition, increased incidences of various malformations, including cardiovascular, have been reported in animals given a prostaglandin synthesis inhibitor during the organogenetic period. Although no teratogenic effects were seen in animal studies, parturition was delayed and prolonged, and there was an increase in the number of stillbirths. Flurbiprofen has been found to cross the placental barrier.

As with other NSAIDs, borderline elevations of one or more liver enzyme tests (AST, ALT, alkaline phosphatase) may occur in up to 15% of patients. 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 function test has occurred, should be evaluated for evidence of the development of a more severe hepatic reaction while on therapy with Ansaid. The ALT test is probably the most sensitive indicator of liver injury. Meaningful (3 times the upper limit of normal) elevations of ALT or AST have been reported in controlled clinical trials in less than 1% of patients.

Severe hepatic reactions including jaundice and cases of fatal hepatitis, liver necrosis and hepatic failure, some of them with fatal outcomes, have been reported with NSAIDs.

Although such reactions are rare, if abnormal liver tests persist or worsen, if clinical signs and symptoms consistent with liver disease develop (e.g. jaundice), or if systemic manifestations occur (e.g. eosinophilia, rash, etc.), this drug should be discontinued.

During long-term therapy, liver function tests should be monitored periodically. If there is a need to prescribe this drug in the presence of impaired liver function, it must be done under strict observation.

As with all NSAIDs, Ansaid (flurbiprofen) should be used with caution in the elderly, particularly women (see Action and Clinical Pharmacology, Pharmacokinetics).

Patients older than 65 years (referred to in this document as older or elderly) and frail or debilitated patients are more susceptible to a variety of adverse reactions from NSAIDs. The incidence of these adverse reactions increases with dose and duration of treatment. In addition, these patients are less tolerant to ulceration and bleeding. Most reports of fatal GI events are in this population. Older patients are also at risk of lower esophageal ulceration and bleeding. For such patients, consideration should be given to a starting dose lower than the one usually recommended, with individual adjustment when necessary, and under close supervision. See information in this section under Endocrine and Metabolism, and Renal for further advice. See also information under Drug Interactions, Glucocorticoids.

Some NSAIDs are associated with persistent urinary symptoms (bladder pain, dysuria, urinary frequency), hematuria or cystitis. The onset of these symptoms may occur at any time after the initiation of therapy with an NSAID. Some cases have become severe on continued treatment. Should urinary symptoms occur, in the absence of an alternate explanation, treatment with Ansaid should be stopped to ascertain if symptoms disappear. This should be done before any urological investigations or treatments are carried out.

Some patients may experience drowsiness, dizziness, blurred vision, vertigo, tinnitus, hearing loss, insomnia or depression with the use of NSAIDs, such as Ansaid. In clinical trials, 1-3% of patients experienced drowsiness, dizziness, vertigo, insomnia or depression with the use of Ansaid. If patients experience these side effects, they should exercise caution in carrying out activities that require alertness.

Frail or debilitated patients may tolerate side effects less well and therefore special care should be taken in treating this population. To minimize the potential risk for an adverse event, the lowest effective dose should be used for the shortest possible duration. As with other NSAIDs, caution should be used in the treatment of elderly patients who are more likely to be suffering from impaired renal, hepatic or cardiac function. For high risk patients, alternate therapies that do not involve NSAIDs should be considered.

Ansaid is not recommended for use with other NSAIDs, with the exception of low-dose ASA for cardiovascular prophylaxis, because of the absence of any evidence demonstrating synergistic benefits and the potential for additive adverse reactions (see Drug Interactions, Drug/Drug Interactions, Acetylsalicylic Acid (ASA) or other NSAIDs). In common with other anti-inflammatory drugs, Ansaid may mask the usual signs of infection.

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 ASA mitigates the increased risk of serious CV thrombotic events associated with NSAID use. The concurrent use of ASA and an NSAID does increase the risk of serious GI events (see Warnings and Precautions, Gastrointestinal (GI)).

Serious GI toxicity (sometimes fatal), such as peptic/duodenal ulceration, inflammation, perforation, obstruction and gastrointestinal bleeding, can occur at any time, with or without warning symptoms, in patients treated with NSAIDs, such as Ansaid. Minor upper GI problems, such as dyspepsia, commonly occur at any time. Health care providers should remain alert for ulceration and bleeding in patients treated with Ansaid, even in the absence of previous GI tract symptoms. Most spontaneous reports of fatal GI events are in elderly or debilitated patients and therefore special care should be taken in treating this population. To minimize the potential risk for an adverse GI event, the lowest effective dose should be used for the shortest possible duration. For high risk patients, alternate therapies that do not involve NSAIDs should be considered (see Warnings and Precautions, Special Populations, Geriatrics (>65 years of age)).

Patients should be informed about the signs and/or symptoms of serious GI toxicity and instructed to discontinue using Ansaid and seek emergency medical attention if they experience any such symptoms. The utility of periodic laboratory monitoring has not been demonstrated, nor has it been adequately assessed. Most patients who develop a serious upper GI adverse event on NSAID therapy have no symptoms. Upper GI ulcers, gross bleeding or perforation, caused by NSAIDs, appear to occur in approximately 1% of patients treated for 3-6 months, and in about 2-4% of patients treated for one year. These trends continue, thus increasing the likelihood of developing a serious GI event at some time during the course of therapy. Even short-term therapy has its risks.

The incidence of these complications increases with increasing dose.

Caution should be taken if prescribing Ansaid to patients with a prior history of peptic/duodenal ulcer disease or gastrointestinal bleeding as these individuals have a greater than 10-fold higher risk for developing a GI bleed when taking a NSAID than patients with neither of these risk factors. In these cases the physician must weigh the benefits of treatment against the possible hazards. Other risk factors for GI ulceration and bleeding include the following: H. pylori infection, increased age, prolonged use of NSAID therapy, excess alcohol intake, smoking, female gender, poor general health status or concomitant therapy with any of the following: Anti-coagulants (e.g. warfarin); Anti-platelet agents (e.g. ASA, clopidogrel); Oral corticosteroids (e.g. prednisone); Selective Serotonin Reuptake Inhibitors (SSRIs) (e.g. citalopram, fluoxetine, paroxetine, sertraline).

Ansaid 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 such as ulcerative colitis and Crohn’s disease. In these cases the physician must weigh the benefits of treatment against the possible hazards.

If ulceration is suspected or confirmed, or if GI bleeding occurs, Ansaid should be discontinued immediately, appropriate treatment instituted and the patient monitored closely.

No studies to date have identified any group of patients not at risk of developing ulceration and bleeding. Studies to date show that all NSAIDs can cause GI tract adverse events as existing data do not clearly identify differences in risk between various NSAIDs.

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 the continuation of Ansaid therapy when and if these adverse reactions appear.

With nonsteroidal anti-inflammatory treatment there is a potential risk of hyperkalemia, particularly in patients with conditions such as diabetes mellitus or renal failure; elderly patients; or in patients receiving concomitant therapy with beta-adrenergic blockers, angiotensin converting enzyme inhibitors or some diuretics. Serum electrolytes should be monitored periodically during long-term therapy, especially in those patients who are at risk.

NSAIDs inhibit platelet aggregation and have been shown to prolong bleeding time in some patients. Unlike acetylsalicylic acid (ASA), their effect on platelet function is quantitatively less, or of shorter duration, and is reversible.

Ansaid and other NSAIDs have no proven efficacy as anti-platelet agents and should not be used as a substitute for ASA or other anti-platelet agents for prophylaxis of cardiovascular thromboembolic diseases. Anti-platelet therapies (e.g. ASA) should not be discontinued. There is some evidence that use of NSAIDs with ASA can markedly attenuate the cardioprotective effects of ASA (see Drug Interactions, Drug-Drug Interactions, Acetylsalicylic Acid (ASA) or other NSAIDs).

Concomitant administration of Ansaid with low dose ASA increases the risk of GI ulceration and associated complications.

(See Contraindications.)

NSAIDs including Ansaid, 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 Ansaid, should be used with caution in patients with hypertension. Blood pressure (BP) should be monitored closely during the initiation of NSAID treatment and throughout the course of therapy.

The use of Ansaid, as with any drug known to inhibit cyclooxygenase/prostaglandin synthesis, may impair fertility and is not recommended in women attempting to conceive. Therefore, in women who have difficulties conceiving, or who are undergoing investigation of infertility, withdrawal of Ansaid should be considered.

Use of NSAIDs, such as Ansaid, can promote sodium retention in a dose-dependent manner, which can lead to fluid retention and edema, and consequences of increased blood pressure and exacerbation of congestive heart failure. Thus, caution should be exercised in prescribing Ansaid in patients with a history of congestive heart failure, compromised cardiac function, hypertension, increased age or other conditions predisposing to fluid retention (see Warnings and Precautions, Cardiovascular).

Use of NSAIDs, such as Ansaid, can increase the risk of hyperkalemia, especially in patients with diabetes mellitus, renal failure, increased age, or those receiving concomitant therapy with adrenergic blockers, angiotensin-converting enzyme inhibitors, angiotensin-II receptor antagonists, cyclosporin, or some diuretics.

Electrolytes should be monitored periodically (see Contraindications).

Ansaid should not be given to patients with complete or partial syndrome of ASA-intolerance (rhinosinusitis, urticaria/angioedema, nasal polyps, asthma) in whom asthma, anaphylaxis, urticaria/angioedema, rhinitis or other allergic manifestations are precipitated by ASA or other NSAIDs. Fatal anaphylactoid reactions have occurred in such individuals. As well, individuals with the above medical problems are at risk of a severe reaction even if they have taken NSAIDs in the past without any adverse reaction (see Contraindications).

When lithium and flurbiprofen are concurrently administered, a reduction in lithium dose is recommended and plasma concentrations of lithium should be monitored. Plasma concentrations of lithium should also be monitored when stopping or starting an NSAID (see Drug Interactions, Lithium).

Patients sensitive to one NSAID may be sensitive to any of the other NSAIDs as well.

Ansaid, in common with other NSAIDs, may mask signs and symptoms of an underlying infectious disease.

Some patients may experience depression with the use of Ansaid (see Warnings and Precautions, Neurologic).

As with NSAIDs in general, anaphylactoid reactions have occurred in patients without known prior exposure to Ansaid. In post-marketing experience, rare cases of anaphylactic anaphylactoid reactions and angioedema have been reported in patients receiving Ansaid. Ansaid should not be given to patients with the ASA-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 ASA or other NSAIDs (see Contraindications).

Anemia is commonly observed in rheumatoid arthritis and is sometimes aggravated by NSAIDs, which may produce fluid retention or minor gastrointestinal blood loss in some patients. Therefore, patients who have initial hemoglobin values of 10 g/dL or less, and who are to receive long-term therapy, should have hemoglobin values determined periodically (see Warnings and Precautions, Hematologic, Blood Dyscrasias).

Concurrent therapy of Ansaid with warfarin requires close monitoring of the international normalized ratio (INR) (see Warnings and Precautions, Hematologic, Anti-coagulants).

(See Contraindications.)

Blood dyscrasias (such as neutropenia, leukopenia, thrombocytopenia, aplastic anemia and agranulocytosis) associated with the use of NSAIDs are rare, but could occur with severe consequences.

Anemia is sometimes seen in patients receiving NSAIDs, including Ansaid. This may be due to fluid retention, GI blood loss, or an incompletely described effect upon erythropoiesis. Patients on long-term treatment with NSAIDs, including Ansaid, should have their hemoglobin or hematocrit checked if they exhibit any signs or symptoms of anemia or blood loss.

(See Warnings and Precautions, Skin.)

(See Warnings and Precautions, Infection, Aseptic Meningitis.)

Blurred and/or diminished vision has been reported with the use of Ansaid and other NSAIDs. Patients experiencing eye complaints should have ophthalmologic examinations (see Warnings and Precautions, Ophthalmologic).

Rarely, with some NSAIDs, the symptoms of aseptic meningitis (stiff neck, severe headaches, nausea and vomiting, fever or clouding of consciousness) have been observed. Patients with autoimmune disorders (systemic lupus erythematosus, mixed connective tissue diseases, etc.) seem to be pre-disposed. Therefore, in such patients, the health care provider must be vigilant to the development of this complication.

In rare cases, serious skin reactions such as Stevens-Johnson syndrome, toxic epidermal necrolysis, exfoliative dermatitis and erythema multiforme have been associated with the use of some NSAIDs. Because the rate of these reactions is low, they have usually been noted during post-marketing surveillance in patients taking other medications also associated with the potential development of these serious skin reactions. Thus, causality is not clear. These reactions are potentially life threatening but may be reversible if the causative agent is discontinued and appropriate treatment instituted. Patients should be advised that if they experience a skin rash they should discontinue their NSAID and contact their physician for assessment and advice, including which additional therapies to discontinue.

Fluid retention and edema have been observed in patients treated with Ansaid. Therefore, as with many other NSAIDs, the possibility of precipitating congestive heart failure in elderly patients or those with compromised cardiac function should be borne in mind. Ansaid should be used with caution in patients with heart failure, hypertension or other conditions predisposing to fluid retention (see Warnings and Precautions, Renal, Fluid and Electrolyte Balance).

The safe use of flurbiprofen during lactation has not been established. Flurbiprofen is secreted in breast milk. The use of this drug is not recommended during lactation (see Contraindications).

Patient with symptoms and/or signs of liver dysfunction, or in whom an abnormal liver function test has occurred, should be monitored carefully for evidence of the development of a more severe hepatic reaction while on therapy with Ansaid. If abnormal liver tests persist or worsen, Ansaid should be discontinued (see Warnings and Precautions, Hepatic/Biliary/Pancreatic).

(Hypertension): Blood pressure should be monitored regularly during therapy with Ansaid (see Warnings and Precautions, Cardiovascular, Hypertension).

Hepatic metabolism may account for >90% of flurbiprofen elimination, so patients with hepatic disease may require reduced doses of Ansaid Tablets compared to patients with normal hepatic function. The pharmacokinetics of R- and S-flurbiprofen were similar, however, in alcoholic cirrhosis patients (N=8) and young healthy volunteers (N=8) following administration of a single 200 mg dose of Ansaid tablets. Flurbiprofen plasma protein binding may be decreased in patients with liver disease and serum albumin concentrations below 3.1 g/dL (see Warnings and Precautions, Hepatic/Biliary/Pancreatic).

With the exception of elderly females, flurbiprofen pharmacokinetics were similar in geriatric arthritis patients, younger arthritis patients, and young healthy volunteers receiving Ansaid Tablets 100 mg as either single or multiple doses. Mean peak serum concentrations of flurbiprofen were higher in the elderly female patients, therefore dosage adjustment may be necessary.

Ansaid is extensively bound (99%) to human plasma protein such as albumin, but less than 10% of the primary albumin binding sites would be occupied by the drug. Flurbiprofen binds to a different primary site on albumin than do anticoagulants, sulfonamides and phenytoin. Mean peak serum concentrations of flurbiprofen were higher in the elderly female patients.

In bioavailability studies in normal volunteers, Ansaid reached peak blood levels in approximately 2 hours (range of 0.5 to 4 hours). Administration of Ansaid with food does not alter total drug availability but delays absorption.

The mode of action of flurbiprofen, like that of other NSAID agents, is not known. However, its therapeutic action is not due to pituitary-adrenal stimulation. Flurbiprofen is an inhibitor of prostaglandin synthesis. The resulting decrease in prostaglandin synthesis may partially explain the drug’s anti-inflammatory effect at the cellular level.

The elimination half life of flurbiprofen is approximately 7 hours with a range of 3 to 9 hours. Excretion of Ansaid is 88-98% complete within 24 hours after the last dose.

Renal clearance is an important route of elimination for flurbiprofen metabolites, but a minor route of elimination for unchanged flurbiprofen (=3% of total clearance). The unbound clearances of R- and S-flurbiprofen did not differ significantly between normal healthy volunteers (N=6, 50 mg single dose) and patients with renal impairment (N=8, inulin clearances ranging from 11 to 43 mL/min, 50 mg multiple doses). Flurbiprofen plasma protein binding may be decreased in patients with renal impairment and serum albumin concentrations below 3.9 g/dL. Elimination of flurbiprofen metabolites may be reduced in patients with renal impairment (Warnings and Precautions, Renal).

Flurbiprofen is not significantly removed from the blood into dialysate in patients undergoing continuous ambulatory peritoneal dialysis.

Ansaid is rapidly metabolized and excreted in the urine as free and unaltered intact drug (20%) and hydroxylated metabolites (50%). About 90% of the flurbiprofen in urine is present as conjugates. In animal models of inflammation the metabolites showed little activity.

Ansaid (flurbiprofen), a phenylalkanoic acid derivative, is a NSAID which also possesses analgesic and antipyretic activities.