FLURBIPROFEN TABLETS USP, 100 mg

• NSAIDs¹ 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).
• Flurbiprofen tablets are contraindicated for the treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery (see WARNINGS).

• NSAIDs cause an increased risk of serious gastrointestinal adverse events including bleeding, ulceration, and perforation of the 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).

Flurbiprofen is a member of the phenylalkanoic acid derivative group of non-steroidal anti-inflammatory drugs. Flurbiprofen tablets USP are round, blue, film-coated tablets for oral administration. Flurbiprofen is a racemic mixture of (+)S- and (-)R- enantiomers. Flurbiprofen is a white or slightly yellow crystalline powder. It is slightly soluble in water at pH 7.0 and readily soluble in most polar solvents. The chemical name is [1,1’-biphenyl]-4-acetic acid,2-fluoro-α-methyl-, (±)-. It has the following structural formula:

C₁₅H₁₃FO₂ M.W. 244.26

Each tablet, for oral administration, contains 100 mg flurbiprofen. In addition, each tablet contains the following inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, polyethylene glycol, polysorbate 80, titanium dioxide, and FD&C Blue #1 aluminum lake.

Flurbiprofen tablets contain flurbiprofen, a non-steroidal anti-inflammatory drug that exhibits anti-inflammatory, analgesic, and antipyretic activities in animal models. The mechanism of action of flurbiprofen, like that of other non-steroidal anti-inflammatory drugs, is not completely understood but may be related to prostaglandin synthetase inhibition.

(see also PRECAUTIONS, Drug Interactions)

Carefully consider the potential benefits and risks of flurbiprofen tablets and other treatment options before deciding to use flurbiprofen tablets. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see WARNINGS).

Flurbiprofen tablets are indicated:

• For relief of the signs and symptoms of rheumatoid arthritis.
• For relief of the signs and symptoms of osteoarthritis.

Flurbiprofen tablets are contraindicated in patients with known hypersensitivity to flurbiprofen.

Flurbiprofen tablets should not be given to patients who have experienced asthma, urticaria, or allergic-type reactions after taking aspirin or other non-steroidal anti-inflammatory drugs. Severe, rarely fatal, anaphylactic-like reactions to non-steroidal anti-inflammatory drugs have been reported in such patients (see WARNINGS, Anaphylactoid Reactions and PRECAUTIONS, Preexisting Asthma).

Flurbiprofen tablets are contraindicated for the treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery (see WARNINGS).

NSAIDs, including flurbiprofen tablets, can cause serious gastrointestinal (GI) adverse events including inflammation, bleeding, ulceration, and perforation of the stomach, small intestine, or large intestine, which can be fatal. These serious adverse events can occur at any time, with or without warning symptoms, in patients treated with NSAIDs. Only one in five patients, who develop a serious upper GI adverse event on NSAID therapy, is symptomatic. Upper GI ulcers, gross bleeding, or perforation caused by NSAIDs occur in approximately 1% of patients treated for 3 to 6 months, and in about 2 to 4% of patients treated for one year. These trends continue with longer duration of use, increasing the likelihood of developing a serious GI event at some time during the course of therapy. However, even short-term therapy is not without risk. NSAIDs should be prescribed with extreme caution in those with a prior history of ulcer disease or gastrointestinal bleeding. Patients with a prior history of peptic ulcer disease and/or gastrointestinal bleeding who use NSAIDs have a greater than 10 fold increased risk for developing a GI bleed compared to patients with neither of these risk factors. Other factors that increase the risk for GI bleeding in patients treated with NSAIDs include concomitant use of oral corticosteroids or anticoagulants, longer duration of NSAID therapy, smoking, use of alcohol, older age, and poor general health status. 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 in patients treated with an NSAID, the lowest effective dose should be used for the shortest possible duration. Patients and physicians should remain alert for signs and symptoms of GI ulcerations and bleeding during NSAID therapy and promptly initiate additional evaluation and treatment if a serious GI event is suspected. This should include discontinuation of the NSAID until a serious GI adverse event is ruled out. For high risk patients, alternate therapies that do not involve NSAIDs should be considered.

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 non-steroidal anti-inflammatory drug 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, 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.

In clinical studies, the elimination half-life of flurbiprofen was unchanged in patients with renal impairment. Flurbiprofen metabolites are eliminated primarily by the kidneys. Elimination of 4’-hydroxy-flurbiprofen was reduced in patients with moderate to severe renal impairment. Therefore, treatment with flurbiprofen tablets is not recommended in these patients with advanced renal disease. If flurbiprofen tablet therapy must be initiated, close monitoring of the patient’s renal function is advisable (see CLINICAL PHARMACOLOGY).

As with other NSAIDs, anaphylactoid reactions may occur in patients without known prior exposure to flurbiprofen tablets. Flurbiprofen tablets 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.

In late pregnancy, as with other NSAIDs, flurbiprofen tablets should be avoided because they may cause premature closure of the ductus arteriosus.

Flurbiprofen tablets 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 flurbiprofen tablets in reducing fever and 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 non-steroidal anti-inflammatory drugs, including flurbiprofen tablets. 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 non-steroidal anti-inflammatory drugs. In addition, rare cases of severe hepatic reactions, including jaundice, 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 with abnormal liver test values, should be evaluated for evidence of the development of a more severe hepatic reaction while on therapy with flurbiprofen tablets. If clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations occur (e.g., eosinophilia, rash, etc.), flurbiprofen tablets should be discontinued.

Anemia is sometimes seen in patients receiving non-steroidal anti-inflammatory drugs, including flurbiprofen tablets. This may be due to fluid retention, GI blood loss, or an incompletely described effect upon erythropoiesis. Patients on long-term treatment with non-steroidal anti-inflammatory drugs, including flurbiprofen tablets, should have their hemoglobin or hematocrit checked periodically even if they do not exhibit any signs or symptoms of anemia.

Non-steroidal anti-inflammatory drugs 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. Flurbiprofen tablets do not generally affect platelet counts, prothrombin time (PT), or partial thromboplastin time (PTT). Patients receiving flurbiprofen tablets 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 non-steroidal anti-inflammatory drugs has been reported in such aspirin-sensitive patients, flurbiprofen tablets should not be administered to patients with this form of aspirin sensitivity and should be used with caution in patients with preexisting asthma.

Blurred and/or diminished vision has been reported with the use of flurbiprofen tablets and other non-steroidal anti-inflammatory drugs. Patients experiencing eye complaints should have ophthalmologic examinations.

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.

• Flurbiprofen tablets, like other NSAIDs, may cause serious CV side effects, such as MI or stroke, which may result in hospitalization and even death. Although serious CV events can occur without warning symptoms, patients should be alert for the signs and symptoms of chest pain, shortness of breath, weakness, slurring of speech, and should ask for medical advice when observing any indicative signs or symptoms. Patients should be apprised of the importance of this follow-up (see WARNINGS, Cardiovascular Effects).
• Flurbiprofen tablets, 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 signs 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).
• Flurbiprofen tablets, 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 bulers, 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.
• Patients should promptly report signs or symptoms of unexplained weight gain or edema to their physicians.
• 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.
• 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).
• In late pregnancy, as with other NSAIDs, flurbiprofen tablets should be avoided because they may cause premature closure of the ductus arteriosus.

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 non-steroidal anti-inflammatory drugs should have their CBC and 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, flurbiprofen tablets should be discontinued.

In rat studies with non-steroidal anti-inflammatory drugs, as with other drugs known to inhibit prostaglandin synthesis, an increased incidence of dystocia, delayed parturition, and decreased pup survival occurred. The effects of flurbiprofen on labor and delivery in pregnant women are unknown.

Concentrations of flurbiprofen in breast milk and plasma of nursing mothers suggest that a nursing infant could receive approximately 0.10 mg flurbiprofen per day in the established milk of a woman taking flurbiprofen tablets 200 mg/day. Because of possible adverse effects of prostaglandin-inhibiting drugs on neonates, 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 have not been established.

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

Clinical experience with flurbiprofen suggests that elderly patients may have a higher incidence of gastrointestinal complaints than younger patients, including ulceration, bleeding, flatulence, bloating, and abdominal pain. To minimize the potential risk for gastrointestinal events, the lowest effective dose should be used for the shortest possible duration (see WARNINGS, Gastrointestinal Effects). Likewise, elderly patients are at greater risk of developing renal decompensation (see WARNINGS, Renal Effects).

The pharmacokinetics of flurbiprofen do not seem to differ in elderly patients from those in younger individuals (see CLINICAL PHARMACOLOGY, Special Populations). The rate of absorption of flurbiprofen was reduced in elderly patients who also received antacids, although the extent of absorption was not affected (see CLINICAL PHARMACOLOGY, Drug-DrugInteractions).

Symptoms following acute overdoses with non-steroidal anti-inflammatory drugs are usually limited to lethargy, drowsiness, nausea, vomiting, and epigastric pain, which are generally reversible with supportive care. Gastrointestinal bleeding can occur. Hypertension, acute renal failure, respiratory depression and coma may occur, but are rare. Anaphylactoid reactions have been reported with therapeutic ingestion of non-steroidal anti-inflammatory drugs, and may occur following an overdose.

Patients should be managed by symptomatic and supportive care following overdose with a non-steroidal anti-inflammatory drug. There are no specific antidotes. Emesis and/or activated charcoal (60 to 100 g in adults, 1 to 2 g/kg in children) and/or osmotic cathartic may be indicated in patients seen within 4 hours of ingestion with symptoms, or following a large overdose (5 to 10 times the usual dose). Forced diuresis, alkalization of urine, hemodialysis, or hemoperfusion may not be useful due to high protein binding.

Carefully consider the potential benefits and risks of flurbiprofen tablets and other treatment options before deciding to use flurbiprofen tablets. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see WARNINGS).

After observing the response to initial therapy with flurbiprofen tablets, the dose and frequency should be adjusted to suit an individual patient's needs.

For relief of the signs and symptoms of rheumatoid arthritis or osteoarthritis, the recommended starting dose of flurbiprofen tablets is 200 to 300 mg per day, divided for administration two, three, or four times a day. The largest recommended single dose in a multiple-dose daily regimen is 100 mg.

Flurbiprofen tablets USP, 100 mg are round, blue, film-coated tablets debossed “93”-“711” available in bottles of 100 and 500.

Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature].

Dispense in a tight, light-resistant container as defined in the USP, with a child-resistant closure (as required).

(See the end of this Medication Guide for a ul of prescription NSAID medicines.)

What is the most important information I should know about medicines called Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)?

NSAID medicines may increase the chance of a heart attack or stroke that can lead to death. This chance increases:

• with longer use of NSAID medicines
• in people who have heart disease

NSAID medicines should never be used right before or after a heart surgery called a “coronary artery bypass graft (CABG).”

NSAID medicines can cause ulcers and bleeding in the stomach and intestines at any time during treatment. Ulcers and bleeding:

• can happen without warning symptoms
• may cause death

The chance of a person getting an ulcer or bleeding increases with:

• taking medicines called “corticosteroids” and “anticoagulants”
• longer use
• smoking
• drinking alcohol
• older age
• having poor health

NSAID medicines should only be used:

• exactly as prescribed
• at the lowest dose possible for your treatment
• for the shortest time needed

What are Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)?

NSAID medicines are used to treat pain and redness, swelling, and heat (inflammation) from medical conditions such as:

• different types of arthritis
• menstrual cramps and other types of short-term pain

Who should not take a Non-Steroidal Anti-Inflammatory Drug (NSAID)?

Do not take an NSAID medicine:

• if you had an asthma attack, hives, or other allergic reaction with aspirin or any other NSAID medicine
• for pain right before or after heart bypass surgery

Tell your healthcare provider:

• about all of your medical conditions.
• about all of the medicines you take. NSAIDs and some other medicines can interact with each other and cause serious side effects. Keep a ul of your medicines to show to your healthcare provider and pharmacist.
• if you are pregnant. NSAID medicines should not be used by pregnant women late in their pregnancy.
• if you are breastfeeding. Talk to your doctor.

What are the possible side effects of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)?

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

Get emergency help right away if you have any of the following symptoms:

• shortness of breath or trouble breathing
• chest pain
• weakness in one part or side of your body
• slurred speech
• swelling of the face or throat

Stop your NSAID medicine and call your healthcare provider right away if you have any of the following symptoms:

• nausea
• more tired or weaker than usual
• itching
• your skin or eyes look yellow
• stomach pain
• flu-like symptoms
• vomit blood
• there is blood in your bowel movement or it is black and sticky like tar
• unusual weight gain
• skin rash or bulers with fever
• swelling of the arms and legs, hands and feet

These are not all the side effects with NSAID medicines. Talk to your healthcare provider or pharmacist for more information about NSAID medicines.

Other information about Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)

• Aspirin is an NSAID medicine but it does not increase the chance of a heart attack. Aspirin can cause bleeding in the brain, stomach, and intestines. Aspirin can also cause ulcers in the stomach and intestines.
• Some of these NSAID medicines are sold in lower doses without a prescription (over-the-counter). Talk to your healthcare provider before using over-the-counter NSAIDs for more than 10 days.

NSAID medicines that need a prescription

This Medication Guide has been approved by the U.S. Food and Drug Administration.