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Class: Other Nonsteroidal Anti-inflammatory Agents
VA Class: MS120
Chemical Name: 2-Fluoro-α-methyl-[1-1′-biphenyl]-acetic acid sodium salt dihydrate
Molecular Formula: C15H13FO2
CAS Number: 56767-76-1
Brands: Ansaid


Special Alerts:

[Posted 07/09/2015]

AUDIENCE: Health Professional, Consumer

ISSUE: FDA is strengthening an existing label warning that non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) increase the chance of a heart attack or stroke. Based on FDAs comprehensive review of new safety information, FDA is requiring updates to the drug labels of all prescription NSAIDs. As is the case with current prescription NSAID labels, the Drug Facts labels of over-the-counter (OTC) non-aspirin NSAIDs already contain information on heart attack and stroke risk. FDA will also request updates to the OTC non-aspirin NSAID Drug Facts labels. See the FDA Drug Safety Communication (Table 1) at: for a list of non-aspirin nonsteroidal anti-inflammatory drug products.

Prescription NSAID labels will be revised to reflect the following information:

  • The risk of heart attack or stroke can occur as early as the first weeks of using an NSAID. The risk may increase with longer use of the NSAID.

  • The risk appears greater at higher doses.

  • It was previously thought that all NSAIDs may have a similar risk. Newer information makes it less clear that the risk for heart attack or stroke is similar for all NSAIDs; however, this newer information is not sufficient for us to determine that the risk of any particular NSAID is definitely higher or lower than that of any other particular NSAID.

  • NSAIDs can increase the risk of heart attack or stroke in patients with or without heart disease or risk factors for heart disease. A large number of studies support this finding, with varying estimates of how much the risk is increased, depending on the drugs and the doses studied.

  • In general, patients with heart disease or risk factors for it have a greater likelihood of heart attack or stroke following NSAID use than patients without these risk factors because they have a higher risk at baseline.

  • Patients treated with NSAIDs following a first heart attack were more likely to die in the first year after the heart attack compared to patients who were not treated with NSAIDs after their first heart attack.

  • There is an increased risk of heart failure with NSAID use.

BACKGROUND: The risk of heart attack and stroke with NSAIDs, either of which can lead to death, was first described in 2005 in the Boxed Warning and Warnings and Precautions sections of the prescription drug labels. Since then, FDA reviewed a variety of new safety information on prescription and OTC NSAIDs, including observational studies, a large combined analysis of clinical trials, and other scientific publications. These studies were also discussed at a joint meeting of the Arthritis Advisory Committee and Drug Safety and Risk Management Advisory Committee held on February 10-11, 2014.

RECOMMENDATION: Patients and health care professionals should remain alert for heart-related side effects the entire time that NSAIDs are being taken. Patients taking NSAIDs should seek medical attention immediately if they experience symptoms such as chest pain, shortness of breath or trouble breathing, weakness in one part or side of their body, or slurred speech.

For more information visit the FDA website at: and .


  • Cardiovascular Risk
  • Possible increased risk of serious (sometimes fatal) cardiovascular thrombotic events (e.g., MI, stroke).1 f Risk may increase with duration of use.1 f Individuals with cardiovascular disease or risk factors for cardiovascular disease may be at increased risk.1 f (See Cardiovascular Effects under Cautions.)

  • Contraindicated for the treatment of pain in the setting of CABG surgery.1 f

  • GI Risk
  • Increased risk of serious (sometimes fatal) GI events (e.g., bleeding, ulceration, perforation of the stomach or intestine).1 f Serious GI events can occur at any time and may not be preceded by warning signs and symptoms.1 f Geriatric individuals are at greater risk for serious GI events.1 f (See GI Effects under Cautions.)


Prototypical NSAIA;1 2 3 6 7 propionic acid derivative.7

Uses for Flurbiprofen

Consider potential benefits and risks of flurbiprofen therapy as well as alternative therapies before initiating therapy with the drug.1 f Use lowest possible effective dosage and shortest duration of therapy consistent with patient’s treatment goals.1 f

Inflammatory Diseases

Symptomatic treatment of rheumatoid arthritis and osteoarthritis.1 2 3 4 5 6 7 10

Also has been used for the management of ankylosing spondylitis.2 6 8 a b

Flurbiprofen Dosage and Administration


  • Consider potential benefits and risks of flurbiprofen therapy as well as alternative therapies before initiating therapy with the drug.1 f


Oral Administration

Administer orally 2–4 times daily.1 13 14

Administration with food or antacids may alter rate but not extent of absorption.1 3 13 g


To minimize the potential risk of adverse cardiovascular and/or GI events, use lowest effective dosage and shortest duration of therapy consistent with the patient’s treatment goals.1 f Adjust dosage based on individual requirements and response; attempt to titrate to the lowest effective dosage.1 f


Inflammatory Diseases
Osteoarthritis or Rheumatoid Arthritis

200–300 mg daily given in 2–4 divided doses.1 3 Similar efficacy whether the total daily dosage of flurbiprofen is administered in 2, 3, or 4 divided doses.2 9

Prescribing Limits


Inflammatory Diseases
Osteoarthritis or Rheumatoid Arthritis

Maximum 100 mg in a single dose.1 3

Special Populations

Renal Impairment

Mild renal impairment: Dosage adjustment not required.1

Moderate or severe renal impairment: Dosage reduction may be necessary.1

Hepatic Impairment

Dosage reduction may be necessary.1 3 15

Geriatric Patients

Use with caution and at the lowest effective dosage for the shortest possible duration.1 f

Cautions for Flurbiprofen


Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

  • Known hypersensitivity to flurbiprofen or any ingredient in the formulation.1 15 f

  • History of asthma, urticaria, or other sensitivity reaction precipitated by aspirin or other NSAIAs.1 f

  • Treatment of perioperative pain in the setting of CABG surgery.1



Cardiovascular Effects

Selective COX-2 inhibitors have been associated with increased risk of cardiovascular events (e.g., MI, stroke) in certain situations.1 16 f Several prototypical NSAIAs also have been associated with increased risk of cardiovascular events.19 20 21 Current data insufficient to assess risk associated with flurbiprofen.19 20 21

Use NSAIAs with caution and careful monitoring (e.g., monitor for development of cardiovascular events) and at the lowest effective dose for the shortest duration necessary.1 f

Short-term use to relieve acute pain, especially at low dosages, does not appear to be associated with increased risk of serious cardiovascular events (except immediately following CABG surgery).1 16 f

No consistent evidence that concomitant use of low-dose aspirin mitigates the increased risk of serious adverse cardiovascular events associated with NSAIAs.1 16 f (See Specific Drugs under Interactions.)

Hypertension and worsening of preexisting hypertension reported; either event may contribute to the increased incidence of cardiovascular events.1 f Use with caution in patients with hypertension; monitor BP.1 f Impaired response to certain diuretics may occur.1 f (See Specific Drugs under Interactions.)

Fluid retention and edema reported.1 f Caution in patients with fluid retention or heart failure.1 f

GI Effects

Serious GI toxicity (e.g., bleeding, ulceration, perforation) can occur with or without warning symptoms; increased risk in those with a history of GI bleeding or ulceration, geriatric patients, smokers, those with alcohol dependence, and those in poor general health.1 15 f h i

For patients at high risk for complications from NSAIA-induced GI ulceration (e.g., bleeding, perforation), consider concomitant use of misoprostol;h j k l alternatively, consider concomitant use of a proton-pump inhibitor (e.g., omeprazole)h j k or use of an NSAIA that is a selective inhibitor of COX-2 (e.g., celecoxib).k

Renal Effects

Direct renal injury, including renal papillary necrosis, reported in patients receiving long-term NSAIA therapy.1 f

Potential for overt renal decompensation.1 f Increased risk of renal toxicity in patients with renal or hepatic impairment or heart failure, in geriatric patients, in patients with volume depletion, and in those receiving a diuretic, ACE inhibitor, or angiotensin II receptor antagonist.1 18 f (See Renal Impairment under Cautions.)

Sensitivity Reactions

Hypersensitivity Reactions

Anaphylactoid reactions reported.1 f

Immediate medical intervention and discontinuance for anaphylaxis.1 f

Avoid in patients with aspirin triad (aspirin sensitivity, asthma, nasal polyps);1 f caution in patients with asthma.1 f

Dermatologic Reactions

Serious skin reactions (e.g., exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis) reported; can occur without warning.1 f Discontinue at first appearance of rash or any other sign of hypersensitivity (e.g., blisters, fever, pruritus).1 f

General Precautions

Hepatic Effects

Severe reactions including jaundice, fatal fulminant hepatitis, liver necrosis, and hepatic failure (sometimes fatal) reported rarely with NSAIAs.1 f

Elevations of serum ALT or AST reported.1 f

Monitor for symptoms and/or signs suggesting liver dysfunction; monitor abnormal liver function test results.1 Discontinue if signs or symptoms of liver disease or systemic manifestations (e.g., eosinophilia, rash) occur.1

Hematologic Effects

Anemia reported rarely.1 Determine hemoglobin concentration or hematocrit periodically in patients receiving long-term therapy even if signs or symptoms of anemia do not occur.1

May inhibit platelet aggregation and prolong bleeding time.1

Ocular Effects

Visual disturbances reported; ophthalmic evaluation recommended if visual changes occur.1

Other Precautions

Not a substitute for corticosteroid therapy; not effective in the management of adrenal insufficiency.1 f

May mask certain signs of infection.1 f

Obtain CBC and chemistry profile periodically during long-term use.1 f

Specific Populations


Category C.1 Avoid use in third trimester because of possible premature closure of the ductus arteriosus.1


Distributed into milk.1 13 15 c d Discontinue nursing or the drug.1

Pediatric Use

Safety and efficacy not established.1

Geriatric Use

Use with caution in patients ≥65 years of age.1 f Geriatric patients appear to tolerate NSAIA therapy less well (e.g., possible higher incidence of adverse GI effects, greater risk of developing renal decompensation) than younger individuals.1 f Fatal adverse GI effects reported more frequently in geriatric patients than younger adults.1 f

Renal Impairment

Metabolites eliminated principally via the kidney.1 3 Use not recommended in patients with advanced renal disease.1 If flurbiprofen must be used, closely monitor renal function.1

Common Adverse Effects

Edema, abdominal pain, constipation, diarrhea, dyspepsia/heartburn, flatulence, GI bleeding, nausea, vomiting, elevated liver enzymes, body weight changes, headache, nervousness, CNS stimulation (e.g., anxiety, insomnia, increased reflexes, tremor), CNS inhibition (e.g., amnesia, asthenia, depression, malaise, somnolence), rhinitis, vision changes, dizziness/vertigo, tinnitus, urinary tract infection, rash.1 f

Interactions for Flurbiprofen

Specific Drugs




ACE inhibitors

Reduced BP response to ACE inhibitor possible1 f

Possible deterioration of renal function in individuals with renal impairment1 f

Monitor BP1 f

Angiotensin II receptor antagonists

Reduced BP response to angiotensin II receptor antagonist possible22

Possible deterioration of renal function in individuals with renal impairment22

Monitor BP22

Antacids (aluminum- and magnesium-containing)

Decrease in rate but not extent of flurbiprofen absorption observed in geriatric patients but not in younger adults1 g

Anticoagulants (e.g., warfarin)

Possible bleeding complications1 f

Caution advised1 f

Antidiabetic agents

Slight reduction in blood glucose concentrations (without signs or symptoms of hypoglycemia)1


Increased risk of GI ulceration or other complications 1

Possible decreased serum flurbiprofen concentrations 1 13 14

No consistent evidence that low-dose aspirin mitigates the increased risk of serious cardiovascular events associated with NSAIAs1 16

Concomitant use not recommended1

β-Adrenergic blocking agents (e.g., atenolol, propranolol)

Potential pharmacologic interaction (reduced antihypertensive effect)1

Pharmacokinetic interaction unlikely1

Monitor BP1


Pharmacokinetic interaction unlikely1

Diuretics (furosemide and thiazides)

Reduced natriuretic effects possible1 f

Monitor for diuretic efficacy and renal failure1 f

Histamine H2-receptor antagonists (cimetidine, ranitidine)

Cimetidine: Small increase in AUC of flurbiprofen, but clinically important pharmacokinetic interaction unlikely1

Ranitidine: Pharmacokinetic interaction unlikely 1


Increased plasma lithium concentrations1 f

Monitor for lithium toxicity1 f


Possible toxicity associated with increased plasma methotrexate concentrations during concomitant NSAIA use1 12 f

Pharmacokinetics of methotrexate not altered during concurrent flurbiprofen administration in one studye

Caution advised1 f

Flurbiprofen Pharmacokinetics



Rapidly and almost completely absorbed following oral administration.1 2 3 13 14 Peak plasma concentrations usually attained within 1.5–3 hours.1 2 m


Food may alter rate but not extent of absorption.1 3 13 g



Distribution into human body tissues and fluids not fully characterized.1

Distributed into milk in very small amounts.1 13 15 c d

Plasma Protein Binding

>99% (principally albumin).1 2 13 14



Extensively metabolized.1 2 13 14 CYP2C9 plays an important role in the metabolism of flurbiprofen to its major metabolite, 4′-hydroxyflurbiprofen, which has weak anti-inflammatory activity.1 2 11

Elimination Route

Following oral dosing, approximately 70% of the flurbiprofen dose is eliminated in urine as parent drug and metabolites, with <3% excreted as unchanged drug.1 3


Approximately 4.7 and 5.7 hours for R- and S-flurbiprofen, respectively.1

Special Populations

In geriatric patients, pharmacokinetic profile similar to that in younger adults.1

In patients with renal impairment, clearance of metabolites may be decreased.1

Not substantially removed by peritoneal dialysis.1







  • Inhibits cyclooxygenase-1 (COX-1) and COX-2.2

  • Pharmacologic actions similar to those of other prototypical NSAIAs; exhibits anti-inflammatory, analgesic, and antipyretic activity.1 2 3 6 7

Advice to Patients

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

  • Importance of reading the medication guide for NSAIAs that is provided to the patient each time the drug is dispensed.1 f

  • Risk of serious cardiovascular events with long-term use.1 f

  • Risk of GI bleeding and ulceration.1 f

  • Risk of serious skin reactions.1 f Risk of anaphylactoid and other sensitivity reactions.1 f

  • Risk of hepatotoxicity.1 f

  • Importance of notifying clinician if signs or symptoms of a cardiovascular event (chest pain, dyspnea, weakness, slurred speech) occur.1 f

  • Importance of discontinuing flurbiprofen and contacting clinician if rash or other signs of hypersensitivity (blisters, fever, pruritus) develop.1 f Importance of seeking immediate medical attention if an anaphylactic reaction occurs.1 f

  • Importance of discontinuing therapy and contacting clinician immediately if signs and symptoms of hepatotoxicity (nausea, fatigue, lethargy, pruritus, jaundice, upper right quadrant tenderness, flu-like symptoms) occur.1 f

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 Importance of avoiding flurbiprofen in late pregnancy (third trimester).1

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.1

  • Importance of informing patients of other important precautionary information.1 (See Cautions.)


Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name



Dosage Forms


Brand Names



Tablets, film-coated

50 mg*



Flurbiprofen Tablets

Caraco, Mylan, Pliva, Sandoz, Teva

100 mg*



Flurbiprofen Tablets

Caraco, Mylan, Pliva, Sandoz, Teva

AHFS DI Essentials. © Copyright 2017, Selected Revisions August 27, 2015. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.


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