Flurbiprofen (oral)

Flurbiprofen (oral)
Black Box Warning
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Alberto Plate [2]

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Black Box Warning

TITLE See full prescribing information for complete Boxed Warning. Condition Name: Cardiovascular Risk NSAIDs 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 tablet, USP is contraindicated for treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery. Gastrointestinal Risk 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

Overview

Flurbiprofen (oral) is an analgesic, NSAID, propionic acid that is FDA approved for the treatment of rheumathoid arthritis and osteoarthritis. There is a Black Box Warning for this drug as shown here. Common adverse reactions include body fluid retention, edema, rash, weight change finding, abdominal pain, constipation, diarrhea, flatulence, heartburn, indigestion, nausea, vomiting, increased liver function test, central nervous system depression, central nervous system stimulation, dizziness, headache, abnormal vision, tinnitus, feeling nervous, rhinitis.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

There is limited information regarding Flurbiprofen (oral) FDA-Labeled Indications and Dosage (Adult) in the drug label.

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Flurbiprofen in adult patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Flurbiprofen in adult patients.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

There is limited information regarding Flurbiprofen (oral) FDA-Labeled Indications and Dosage (Pediatric) in the drug label.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Flurbiprofen in pediatric patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Flurbiprofen in pediatric patients.

Contraindications

Flurbiprofen tablets, USP are contraindicated in patients with known hypersensitivity to flurbiprofen. Flurbiprofen tablet, USP should not be given to patients who have experienced asthma, urticaria, or allergic-type reactions after taking aspirin or other nonsteroidal anti-inflammatory drugs. Severe, rarely fatal, anaphylactic-like reactions to nonsteroidal anti-inflammatory drugs have been reported in such patients.

Flurbiprofen tablet, USP is contraindicated for the treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery.

Warnings

TITLE See full prescribing information for complete Boxed Warning. Condition Name: Cardiovascular Risk NSAIDs 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 tablet, USP is contraindicated for treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery. Gastrointestinal Risk 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

Cardiovascular Effects

Cardiovascular Thrombotic Events

Clinical trials of several COX-2 selective and nonselective NSAIDs of up to three years duration have shown an increased risk of serious cardiovascular (CV) thrombotic events, myocardial infarction, and stroke, which can be fatal. All NSAIDs, both COX-2 selective and nonselective, may have a similar risk. Patients with known CV disease or risk factors for CV disease may be at greater risk. To minimize the potential risk for an adverse CV event in patients treated with an NSAID, the lowest effective dose should be used for the shortest duration possible. 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 aspirin mitigates the increased risk of serious CV thrombotic events associated with NSAID use. The concurrent use of aspirin and an NSAID does increase the risk of serious GI events.

Two large, controlled clinical trials of a COX-2 selective NSAID for the treatment of pain in the first 10-14 days following CABG surgery found an increased incidence of myocardial infarction and stroke.

Hypertension

NSAIDs including Flurbiprofen tablet, USP, 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 Flurbiprofen tablet, USP, 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.

Congestive Heart Failure and Edema

Fluid retention and edema have been observed in some patients taking NSAIDs. Flurbiprofen tablet, USP should be used with caution in patients with fluid retention or heart failure.

Gastrointestinal Effects - Risk of Ulceration, Bleeding, and Perforation

NSAIDs, including Flurbiprofen tablet, USP, 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 3-6 months, and in about 2-4% 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 treated with neither of these risk factors. Other factors that increase the risk of 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.

Renal Effects

Long-term administration of NSAIDs has resulted in renal papillary necrosis and other renal injury. Renal toxicity has also been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion. In these patients, administration of a nonsteroidal anti-inflammatory drug may cause a dose-dependent reduction in prostaglandin formation and, secondarily, in renal blood flow, which may precipitate overt renal 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.

Advanced Renal Disease

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 tablet, USP is not recommended in these patients with advanced renal disease. If Flurbiprofen tablet, USP therapy must be initiated, close monitoring of the patients renal function is advisable.

Anaphylactoid Reactions

As with other NSAIDs, anaphylactoid reactions may occur in patients without known prior exposure to Flurbiprofen tablet, USP. Flurbiprofen tablet, USP 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. Emergency help should be sought in cases where an anaphylactoid reaction occurs.

Pregnancy

In late pregnancy, as with other NSAIDs, Flurbiprofen tablet, USP should be avoided because it may cause premature closure of the ductus arteriosus.

Adverse Reactions

Clinical Trials Experience

Postmarketing Experience

There is limited information regarding Flurbiprofen (oral) Postmarketing Experience in the drug label.

Drug Interactions

There is limited information regarding Flurbiprofen (oral) Drug Interactions in the drug label.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): There is no FDA guidance on usage of Flurbiprofen (oral) in women who are pregnant.
Pregnancy Category (AUS): There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Flurbiprofen (oral) in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Flurbiprofen (oral) during labor and delivery.

Nursing Mothers

There is no FDA guidance on the use of Flurbiprofen (oral) in women who are nursing.

Pediatric Use

There is no FDA guidance on the use of Flurbiprofen (oral) in pediatric settings.

Geriatic Use

There is no FDA guidance on the use of Flurbiprofen (oral) in geriatric settings.

Gender

There is no FDA guidance on the use of Flurbiprofen (oral) with respect to specific gender populations.

Race

There is no FDA guidance on the use of Flurbiprofen (oral) with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Flurbiprofen (oral) in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Flurbiprofen (oral) in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Flurbiprofen (oral) in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Flurbiprofen (oral) in patients who are immunocompromised.

Administration and Monitoring

Administration

There is limited information regarding Flurbiprofen (oral) Administration in the drug label.

Monitoring

There is limited information regarding Flurbiprofen (oral) Monitoring in the drug label.

IV Compatibility

There is limited information regarding the compatibility of Flurbiprofen (oral) and IV administrations.

Overdosage

Symptoms following acute overdoses with nonsteroidal 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 nonsteroidal anti-inflammatory drugs, and may occur following an overdose.

Patients should be managed by symptomatic and supportive care following overdose with a nonsteroidal 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.

Pharmacology

1 : 1 mixture (racemate)Flurbiprofen
Systematic (IUPAC) name
(RS)-2-(2-fluorobiphenyl-4-yl)propanoic acid
Identifiers
CAS number	5104-49-4
ATC code	M01AE09 , M02AA19 (WHO), R02AX01 (WHO), S01BC04 (WHO)
PubChem	3394
DrugBank	DB00712
Chemical data
Formula	Template:OrganicBox atomTemplate:OrganicBox atomTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBox atomTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBox atomTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBox
Mol. mass	244.261 g/mol
SMILES	eMolecules & PubChem
Synonyms	(±)-2-fluoro-α-methyl-(1,1'-biphenyl)-4-acetic acid
Physical data
Melt. point	117 °C (243 °F)
Pharmacokinetic data
Bioavailability	?
Protein binding	> 99%
Metabolism	Hepatic (CYP2C9)
Half life	4.7-5.7 hours
Excretion	Renal
Therapeutic considerations
Pregnancy cat.	C (U.S.), B2 (Au)
Legal status	POM
Routes	Oral

Mechanism of Action

There is limited information regarding Flurbiprofen (oral) Mechanism of Action in the drug label.

Structure

The chemical name is [1,1'-biphenyl]-4-acetic acid, 2-fluoro-alphamethyl-, (±)-. The molecular weight is 244.26. Its molecular formula is C15H13FO2 and it has the following structural formula:

Pharmacodynamics

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

Pharmacokinetics

Pharmacokinetics

Absorption

The mean oral bioavailability of flurbiprofen from Flurbiprofen tablet, USP 100 mg is 96% relative to an oral solution. Flurbiprofen is rapidly and non-stereoselectively absorbed from Flurbiprofen tablet, USP, with peak plasma concentrations occurring at about 2 hours. Administration of Flurbiprofen tablet, USP with either food or antacids may alter the rate but not the extent of flurbiprofen absorption. Ranitidine has been shown to have no effect on either the rate or extent of flurbiprofen absorption from Flurbiprofen tablet, USP.

Distribution

The apparent volume of distribution (Vz/F) of both R- and S-flurbiprofen is approximately 0.12 L/Kg. Both flurbiprofen enantiomers are more than 99% bound to plasma proteins, primarily albumin. Plasma protein binding is relatively constant for the typical average steady-state concentrations (≤10 µg/mL) achieved with recommended doses. Flurbiprofen is poorly excreted into human milk. The nursing infant dose is predicted to be approximately 0.1 mg/day in the established milk of a woman taking Flurbiprofen tablet, USP 200 mg/day.

Metabolism

Several flurbiprofen metabolites have been identified in human plasma and urine. These metabolites include 4'-hydroxy-flurbiprofen, 3', 4'-dihydroxy-flurbiprofen, 3'-hydroxy-4'-methoxy-flurbiprofen, their conjugates, and conjugated flurbiprofen. Unlike other arylpropionic acid derivatives (eg, ibuprofen), metabolism of R-flurbiprofen to S-flurbiprofen is minimal. In vitro studies have demonstrated that cytochrome P450 2C9 plays an important role in the metabolism of flurbiprofen to its major metabolite, 4'-hydroxy-flurbiprofen. The 4'-hydroxy-flurbiprofen metabolite showed little anti-inflammatory activity in animal models of inflammation. Flurbiprofen does not induce enzymes that alter its metabolism.

The total plasma clearance of unbound flurbiprofen is not stereoselective, and clearance of flurbiprofen is independent of dose when used within the therapeutic range.

Excretion

Following dosing with Flurbiprofen tablet, USP, less than 3% of flurbiprofen is excreted unchanged in the urine, with about 70% of the dose eliminated in the urine as parent drug and metabolites. Because renal elimination is a significant pathway of elimination of flurbiprofen metabolites, dosing adjustment in patients with moderate or severe renal dysfunction may be necessary to avoid accumulation of flurbiprofen metabolites. The mean terminal disposition half-lives (t½) of R- and S-flurbiprofen are similar, about 4.7 and 5.7 hours, respectively. There is little accumulation of flurbiprofen following multiple doses of Flurbiprofen tablet, USP.

Nonclinical Toxicology

There is limited information regarding Flurbiprofen (oral) Nonclinical Toxicology in the drug label.

Clinical Studies

There is limited information regarding Flurbiprofen (oral) Clinical Studies in the drug label.

How Supplied

There is limited information regarding Flurbiprofen (oral) How Supplied in the drug label.

Storage

There is limited information regarding Flurbiprofen (oral) Storage in the drug label.

Images

Drug Images

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Package and Label Display Panel

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Patient Counseling Information

There is limited information regarding Flurbiprofen (oral) Patient Counseling Information in the drug label.

Precautions with Alcohol

Alcohol-Flurbiprofen interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

There is limited information regarding Flurbiprofen (oral) Brand Names in the drug label.

Look-Alike Drug Names

There is limited information regarding Flurbiprofen (oral) Look-Alike Drug Names in the drug label.

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

Flurbiprofen (oral)

File:Flurbiprofen.svg
Clinical data
Pregnancy category	C (U.S.), B2 (Au)
Routes of administration	Oral
ATC code	M01AE09 (WHO) M02AA19 (WHO), S01BC04 (WHO)
Pharmacokinetic data
Protein binding	> 99%
Metabolism	Hepatic (CYP2C9)
Elimination half-life	4.7-5.7 hours
Excretion	Renal
Identifiers
IUPAC name 2-(3-fluoro-4-phenyl-phenyl)propanoic acid
CAS Number	5104-49-4
PubChem CID	3394
DrugBank	APRD00753
E number	{{#property:P628}}
ECHA InfoCard	{{#property:P2566}}
Chemical and physical data
Formula	C15H13FO2
Molar mass	244.261 g/mol

Flurbiprofen is a member of the phenylalkanoic acid derivative family of non-steroidal anti-inflammatory drugs (NSAIDs) used to treat the inflammation and pain of arthritis. It is also known by the trade name ANSAID and marketed by Pfizer.

Flurbiprofen is also used as an active ingredient in some kinds of throat lozenges.

R-flurbiprofen is the single enantiomer of racemate flurbiprofen; this compound is currently in clinical trials for the treatment of metastatic prostate cancer, and Alzheimer's disease.

Flurbiprofen was mocked by television satirist Stephen Colbert (for its unlikely name) during an interview with Terry Gross aired on October 9, 2007 on National Public Radio's program "Fresh Air." Colbert had been taking the drug after breaking his wrist earlier that year.