×
Overview
What is FLURBIPROFEN?
Flurbiprofen is a member of the phenylalkanoic acid derivative
group of non-steroidal anti-inflammatory drugs. Flurbiprofen tablets are beige,
round, film-coated tablets for oral administration. Flurbiprofen is a racemic
mixture of (+)S- and (-)R-enantiomers. Flurbiprofen, USP 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-alpha-methyl-, (±)-. The molecular weight is 244.26. Its
molecular formula is CHFO and it has the following structural formula
Each tablet, for oral administration, contains 50 mg or 100 mg flurbiprofen,
USP. Inactive ingredients are colloidal silicon dioxide, croscarmellose sodium,
hypromellose, lactose (anhydrous), magnesium stearate, microcrystalline
cellulose, polydextrose, polyethylene glycol, sodium lauryl sulfate, titanium
dioxide, triacetin, yellow iron oxide and black iron oxide.
What does FLURBIPROFEN look like?
What are the available doses of FLURBIPROFEN?
Sorry No records found.
What should I talk to my health care provider before I take FLURBIPROFEN?
Sorry No records found
How should I use FLURBIPROFEN?
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 ).
Flurbiprofen tablets are indicated:
Carefully consider the potential benefits and risks of
flurbiprofen and other treatment options before deciding to use flurbiprofen.
Use the lowest effective dose for the shortest duration consistent with
individual patient treatment goals (see ).
After observing the response to initial therapy with flurbiprofen, 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 is 200 mg 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.
What interacts with FLURBIPROFEN?
Sorry No Records found
What are the warnings of FLURBIPROFEN?
Sorry No Records found
What are the precautions of FLURBIPROFEN?
Sorry No Records found
What are the side effects of FLURBIPROFEN?
Sorry No records found
What should I look out for while using FLURBIPROFEN?
Flurbiprofen tablets are contraindicated in patients with known
hypersensitivity to flurbiprofen tablets or the excipients (see ).
Flurbiprofen 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 and
).
Flurbiprofen is contraindicated for the treatment of perioperative pain in
the setting of coronary artery bypass graft (CABG) surgery (see ).
What might happen if I take too much FLURBIPROFEN?
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 g 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.
How should I store and handle FLURBIPROFEN?
Store bottles of 1000 SINGULAIR 5-mg chewable tablets and 8000 SINGULAIR 10-mg film-coated tablets at 25°C (77°F), excursions permitted to 15-30°C (59-86°F) [see USP Controlled Room Temperature]. Protect from moisture and light. Store in original container. When product container is subdivided, repackage into a well-closed, light resistant container. Flurbiprofen tablets, USP are available containing 50 mg or 100
mg of flurbiprofen, USP.The 50 mg tablets are film-coated beige, round, unscored tablets debossed
with over on one side of
the tablet and blank on the other side. They are available as follows:NDC 0378-0076-01bottles of 100 tabletsThe 100 mg tablets are film-coated beige, round, unscored, tablets debossed
with over on one side of
the tablet and blank on the other side. They are available as follows:NDC 0378-0093-01bottles of 100 tabletsNDC 0378-0093-05bottles of 500 tabletsStore at 20° to 25°C (68° to 77°F). [See USP for Controlled Room
Temperature.]Protect from light.Dispense in a tight, light-resistant container as defined in the USP using a
child-resistant closure.PHARMACIST:Mylan Pharmaceuticals Inc.Morgantown, WV 26505REVISED SEPTEMBER 2007FRB:R8mcFlurbiprofen tablets, USP are available containing 50 mg or 100
mg of flurbiprofen, USP.The 50 mg tablets are film-coated beige, round, unscored tablets debossed
with over on one side of
the tablet and blank on the other side. They are available as follows:NDC 0378-0076-01bottles of 100 tabletsThe 100 mg tablets are film-coated beige, round, unscored, tablets debossed
with over on one side of
the tablet and blank on the other side. They are available as follows:NDC 0378-0093-01bottles of 100 tabletsNDC 0378-0093-05bottles of 500 tabletsStore at 20° to 25°C (68° to 77°F). [See USP for Controlled Room
Temperature.]Protect from light.Dispense in a tight, light-resistant container as defined in the USP using a
child-resistant closure.PHARMACIST:Mylan Pharmaceuticals Inc.Morgantown, WV 26505REVISED SEPTEMBER 2007FRB:R8mcFlurbiprofen tablets, USP are available containing 50 mg or 100
mg of flurbiprofen, USP.The 50 mg tablets are film-coated beige, round, unscored tablets debossed
with over on one side of
the tablet and blank on the other side. They are available as follows:NDC 0378-0076-01bottles of 100 tabletsThe 100 mg tablets are film-coated beige, round, unscored, tablets debossed
with over on one side of
the tablet and blank on the other side. They are available as follows:NDC 0378-0093-01bottles of 100 tabletsNDC 0378-0093-05bottles of 500 tabletsStore at 20° to 25°C (68° to 77°F). [See USP for Controlled Room
Temperature.]Protect from light.Dispense in a tight, light-resistant container as defined in the USP using a
child-resistant closure.PHARMACIST:Mylan Pharmaceuticals Inc.Morgantown, WV 26505REVISED SEPTEMBER 2007FRB:R8mcFlurbiprofen tablets, USP are available containing 50 mg or 100
mg of flurbiprofen, USP.The 50 mg tablets are film-coated beige, round, unscored tablets debossed
with over on one side of
the tablet and blank on the other side. They are available as follows:NDC 0378-0076-01bottles of 100 tabletsThe 100 mg tablets are film-coated beige, round, unscored, tablets debossed
with over on one side of
the tablet and blank on the other side. They are available as follows:NDC 0378-0093-01bottles of 100 tabletsNDC 0378-0093-05bottles of 500 tabletsStore at 20° to 25°C (68° to 77°F). [See USP for Controlled Room
Temperature.]Protect from light.Dispense in a tight, light-resistant container as defined in the USP using a
child-resistant closure.PHARMACIST:Mylan Pharmaceuticals Inc.Morgantown, WV 26505REVISED SEPTEMBER 2007FRB:R8mcFlurbiprofen tablets, USP are available containing 50 mg or 100
mg of flurbiprofen, USP.The 50 mg tablets are film-coated beige, round, unscored tablets debossed
with over on one side of
the tablet and blank on the other side. They are available as follows:NDC 0378-0076-01bottles of 100 tabletsThe 100 mg tablets are film-coated beige, round, unscored, tablets debossed
with over on one side of
the tablet and blank on the other side. They are available as follows:NDC 0378-0093-01bottles of 100 tabletsNDC 0378-0093-05bottles of 500 tabletsStore at 20° to 25°C (68° to 77°F). [See USP for Controlled Room
Temperature.]Protect from light.Dispense in a tight, light-resistant container as defined in the USP using a
child-resistant closure.PHARMACIST:Mylan Pharmaceuticals Inc.Morgantown, WV 26505REVISED SEPTEMBER 2007FRB:R8mcFlurbiprofen tablets, USP are available containing 50 mg or 100
mg of flurbiprofen, USP.The 50 mg tablets are film-coated beige, round, unscored tablets debossed
with over on one side of
the tablet and blank on the other side. They are available as follows:NDC 0378-0076-01bottles of 100 tabletsThe 100 mg tablets are film-coated beige, round, unscored, tablets debossed
with over on one side of
the tablet and blank on the other side. They are available as follows:NDC 0378-0093-01bottles of 100 tabletsNDC 0378-0093-05bottles of 500 tabletsStore at 20° to 25°C (68° to 77°F). [See USP for Controlled Room
Temperature.]Protect from light.Dispense in a tight, light-resistant container as defined in the USP using a
child-resistant closure.PHARMACIST:Mylan Pharmaceuticals Inc.Morgantown, WV 26505REVISED SEPTEMBER 2007FRB:R8mcFlurbiprofen tablets, USP are available containing 50 mg or 100
mg of flurbiprofen, USP.The 50 mg tablets are film-coated beige, round, unscored tablets debossed
with over on one side of
the tablet and blank on the other side. They are available as follows:NDC 0378-0076-01bottles of 100 tabletsThe 100 mg tablets are film-coated beige, round, unscored, tablets debossed
with over on one side of
the tablet and blank on the other side. They are available as follows:NDC 0378-0093-01bottles of 100 tabletsNDC 0378-0093-05bottles of 500 tabletsStore at 20° to 25°C (68° to 77°F). [See USP for Controlled Room
Temperature.]Protect from light.Dispense in a tight, light-resistant container as defined in the USP using a
child-resistant closure.PHARMACIST:Mylan Pharmaceuticals Inc.Morgantown, WV 26505REVISED SEPTEMBER 2007FRB:R8mcFlurbiprofen tablets, USP are available containing 50 mg or 100
mg of flurbiprofen, USP.The 50 mg tablets are film-coated beige, round, unscored tablets debossed
with over on one side of
the tablet and blank on the other side. They are available as follows:NDC 0378-0076-01bottles of 100 tabletsThe 100 mg tablets are film-coated beige, round, unscored, tablets debossed
with over on one side of
the tablet and blank on the other side. They are available as follows:NDC 0378-0093-01bottles of 100 tabletsNDC 0378-0093-05bottles of 500 tabletsStore at 20° to 25°C (68° to 77°F). [See USP for Controlled Room
Temperature.]Protect from light.Dispense in a tight, light-resistant container as defined in the USP using a
child-resistant closure.PHARMACIST:Mylan Pharmaceuticals Inc.Morgantown, WV 26505REVISED SEPTEMBER 2007FRB:R8mcFlurbiprofen tablets, USP are available containing 50 mg or 100
mg of flurbiprofen, USP.The 50 mg tablets are film-coated beige, round, unscored tablets debossed
with over on one side of
the tablet and blank on the other side. They are available as follows:NDC 0378-0076-01bottles of 100 tabletsThe 100 mg tablets are film-coated beige, round, unscored, tablets debossed
with over on one side of
the tablet and blank on the other side. They are available as follows:NDC 0378-0093-01bottles of 100 tabletsNDC 0378-0093-05bottles of 500 tabletsStore at 20° to 25°C (68° to 77°F). [See USP for Controlled Room
Temperature.]Protect from light.Dispense in a tight, light-resistant container as defined in the USP using a
child-resistant closure.PHARMACIST:Mylan Pharmaceuticals Inc.Morgantown, WV 26505REVISED SEPTEMBER 2007FRB:R8mcFlurbiprofen tablets, USP are available containing 50 mg or 100
mg of flurbiprofen, USP.The 50 mg tablets are film-coated beige, round, unscored tablets debossed
with over on one side of
the tablet and blank on the other side. They are available as follows:NDC 0378-0076-01bottles of 100 tabletsThe 100 mg tablets are film-coated beige, round, unscored, tablets debossed
with over on one side of
the tablet and blank on the other side. They are available as follows:NDC 0378-0093-01bottles of 100 tabletsNDC 0378-0093-05bottles of 500 tabletsStore at 20° to 25°C (68° to 77°F). [See USP for Controlled Room
Temperature.]Protect from light.Dispense in a tight, light-resistant container as defined in the USP using a
child-resistant closure.PHARMACIST:Mylan Pharmaceuticals Inc.Morgantown, WV 26505REVISED SEPTEMBER 2007FRB:R8mcFlurbiprofen tablets, USP are available containing 50 mg or 100
mg of flurbiprofen, USP.The 50 mg tablets are film-coated beige, round, unscored tablets debossed
with over on one side of
the tablet and blank on the other side. They are available as follows:NDC 0378-0076-01bottles of 100 tabletsThe 100 mg tablets are film-coated beige, round, unscored, tablets debossed
with over on one side of
the tablet and blank on the other side. They are available as follows:NDC 0378-0093-01bottles of 100 tabletsNDC 0378-0093-05bottles of 500 tabletsStore at 20° to 25°C (68° to 77°F). [See USP for Controlled Room
Temperature.]Protect from light.Dispense in a tight, light-resistant container as defined in the USP using a
child-resistant closure.PHARMACIST:Mylan Pharmaceuticals Inc.Morgantown, WV 26505REVISED SEPTEMBER 2007FRB:R8mcFlurbiprofen tablets, USP are available containing 50 mg or 100
mg of flurbiprofen, USP.The 50 mg tablets are film-coated beige, round, unscored tablets debossed
with over on one side of
the tablet and blank on the other side. They are available as follows:NDC 0378-0076-01bottles of 100 tabletsThe 100 mg tablets are film-coated beige, round, unscored, tablets debossed
with over on one side of
the tablet and blank on the other side. They are available as follows:NDC 0378-0093-01bottles of 100 tabletsNDC 0378-0093-05bottles of 500 tabletsStore at 20° to 25°C (68° to 77°F). [See USP for Controlled Room
Temperature.]Protect from light.Dispense in a tight, light-resistant container as defined in the USP using a
child-resistant closure.PHARMACIST:Mylan Pharmaceuticals Inc.Morgantown, WV 26505REVISED SEPTEMBER 2007FRB:R8mc
×
Clinical Information
Chemical Structure
No Image found
Clinical Pharmacology
Flurbiprofen is 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.
The mean oral bioavailability of flurbiprofen 100 mg tablets is
96% relative to an oral solution. Flurbiprofen is rapidly and
non-stereoselectively absorbed with peak plasma concentrations occurring at
about 2 hours (see ). Administration of flurbiprofen
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.
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 mcg/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
200 mg/day (see ).
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 (e.g.,
ibuprofen), metabolism of R-flurbiprofen to S-flurbiprofen is minimal. 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.
Following dosing with flurbiprofen, 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 (t) 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.
The pharmacokinetics of flurbiprofen have not been investigated
in pediatric patients.
No pharmacokinetic differences due to race have been
identified.
Flurbiprofen pharmacokinetics were similar in geriatric arthritis
patients, younger arthritis patients, and young healthy volunteers receiving
flurbiprofen tablets 100 mg as either single or multiple doses.
Hepatic metabolism may account for > 90% of flurbiprofen
elimination, so patients with hepatic disease may require reduced doses of
flurbiprofen 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 flurbiprofen tablets.
Flurbiprofen plasma protein binding may be decreased in patients with liver
disease and serum albumin concentrations below 3.1 g/dL (see ).
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 (see ).
Flurbiprofen is not significantly removed from the blood into dialysate in
patients undergoing continuous ambulatory peritoneal dialysis.
(see also )
Administration of flurbiprofen to volunteers under fasting
conditions or with antacid suspension yielded similar serum flurbiprofen-time
profiles in young adult subjects (n = 12). In geriatric subjects (n = 7), there
was a reduction in the rate but not the extent of flurbiprofen absorption.
Concurrent administration of flurbiprofen and aspirin resulted in
50% lower serum flurbiprofen concentrations. This effect of aspirin (which is
also seen with other non-steroidal anti-inflammatory drugs) has been
demonstrated in patients with rheumatoid arthritis (n = 15) and in healthy
volunteers (n = 16) (see ).
The effect of flurbiprofen on blood pressure response to
propranolol and atenolol was evaluated in men with mild uncomplicated
hypertension (n = 10). Flurbiprofen pretreatment attenuated the hypotensive
effect of a single dose of propranolol but not atenolol. Flurbiprofen did not
appear to affect the beta-blocker-mediated reduction in heart rate. Flurbiprofen
did not affect the pharmacokinetic profile of either drug (see ).
In normal volunteers (n = 9), pretreatment with cimetidine or
ranitidine did not affect flurbiprofen pharmacokinetics, except for a small
(13%) but statistically significant increase in the area under the serum
concentration curve of flurbiprofen in subjects who received cimetidine.
In studies of healthy males (n = 14), concomitant administration
of flurbiprofen and digoxin did not change the steady-state serum levels of
either drug.
Studies in healthy volunteers have shown that, like other
non-steroidal anti-inflammatory drugs, flurbiprofen can interfere with the
effects of furosemide. Although results have varied from study to study, effects
have been shown on furosemide-stimulated diuresis, natriuresis, and kaliuresis.
Other non-steroidal anti-inflammatory drugs that inhibit prostaglandin synthesis
have been shown to interfere with thiazide and potassium-sparing diuretics (see
).
In a study of 11 women with bipolar disorder receiving lithium
carbonate at a dosage of 600 mg to 1200 mg/day, administration of 100 mg
flurbiprofen every 12 hours increased plasma lithium concentrations by 19%. Four
of 11 patients experienced a clinically important increase (> 25% or > 0.2
mmol/L). Non-steroidal anti-inflammatory drugs have also been reported to
decrease the renal clearance of lithium by about 20% (see ).
In a study of six adult arthritis patients, coadministration of
methotrexate (10 to 25 mg/dose) and flurbiprofen (300 mg/day) resulted in no
observable interaction between these two drugs.
In a clinical study, flurbiprofen was administered to adult
diabetics who were already receiving glyburide (n = 4), metformin (n = 2),
chlorpropamide with phenformin (n = 3), or glyburide with phenformin (n = 6).
Although there was a slight reduction in blood sugar concentrations during
concomitant administration of flurbiprofen and hypoglycemic agents, there were
no signs or symptoms of hypoglycemia.
Non-Clinical Toxicology
Flurbiprofen tablets are contraindicated in patients with known
hypersensitivity to flurbiprofen tablets or the excipients (see ).
Flurbiprofen 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 and
).
Flurbiprofen is contraindicated for the treatment of perioperative pain in
the setting of coronary artery bypass graft (CABG) surgery (see ).
In vitro drug metabolism studies suggest that there is a potential for drug interactions when trazodone is given with CYP3A4 inhibitors. Ritonavir, a potent CYP3A4 inhibitor, increased the Cmax, AUC, and elimination half-life, and decreased clearance of trazodone after administration of ritonavir twice daily for 2 days. Adverse effects including nausea, hypotension, and syncope were observed when ritonavir and trazodone were co-administered. It is likely that ketoconazole, indinavir, and other CYP3A4 inhibitors such as intraconazole or nefazadone may lead to substantial increases in trazodone plasma concentrations, with the potential for adverse effects. If trazodone is used with a potent CYP3A4 inhibitor, a lower dose of trazodone should be considered.
Carbamazepine reduced plasma concentrations of trazodone when co-administered. Patients should be more closely monitored to see if there is a need for an increased dose of trazodone when taking both drugs.
Increased serum digoxin or phenytoin levels have been reported to occur in patients receiving trazodone concurrently with either of those two drugs.
It is not known whether interactions will occur between monoamine oxidase (MAO) inhibitors and trazodone HCl. Due to the absence of clinical experience, if MAO inhibitors are discontinued shortly before or are to be given concomitantly with trazodone HCl, therapy should be initiated cautiously with gradual increase in dosage until optimum response is achieved.
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 (see ).
Two large, controlled, clinical trials of a COX-2 selective NSAID for the
treatment of pain in the first 10 to 14 days following CABG surgery found an
increased incidence of myocardial infarction and stroke (see ).
NSAIDs, including flurbiprofen, can lead to onset of new
hypertension or worsening of preexisting 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, 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.
Fluid retention and edema have been observed in some patients
taking NSAIDs. Flurbiprofen should be used with caution in patients with fluid
retention or heart failure.
NSAIDs, including flurbiprofen, 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 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.
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 is not recommended in these patients with advanced
renal disease. If flurbiprofen therapy must be initiated, close monitoring of
the patients renal function is advisable (see ).
As with other NSAIDs, anaphylactoid reactions may occur in
patients without known prior exposure to flurbiprofen. Flurbiprofen 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 and ). Emergency
help should be sought in cases where an anaphylactoid reaction occurs.
In late pregnancy, as with other NSAIDs, flurbiprofen should be
avoided because it may cause premature closure of the ductus arteriosus.
Flurbiprofen 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 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. 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. If
clinical signs and symptoms consistent with liver disease develop, or if
systemic manifestations occur (e.g., eosinophilia, rash, etc.), flurbiprofen
should be discontinued.
Anemia is sometimes seen in patients receiving non-steroidal
anti-inflammatory drugs, including flurbiprofen. 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, 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 does not generally affect platelet counts, prothrombin
time (PT), or partial thromboplastin time (PTT). Patients receiving flurbiprofen
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 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 and other non-steroidal anti-inflammatory drugs. Patients
experiencing eye complaints should have ophthalmologic examinations
