Flurbiprofen (Froben) is a non-selective non-steroidal anti-inflammatory drug that is used in the treatment of mild to moderate pain and inflammatory conditions. Compared to Ibuprofen, it has a longer half-life and therefore it can be taken twice daily. It also has greater anti-inflammatory and antipyretic properties.
Indications of Flurbiprofen (Froben):
-
Rheumatoid arthritis and osteoarthritis:
- Both osteoarthritis (OA) and rheumatoid arthritis (RA) can be effectively treated with it.
- Canadian labeling: Additional use (not in US labeling):
- It is used for relieving signs and symptoms of ankylosing spondylitis, pain associated with dysmenorrhea, mild to moderate pain accompanied by inflammation (eg, bursitis, tendonitis, and soft tissue trauma).
-
Off Label Use of Flurbiprofen in Adults:
- For the management of postoperative pain.
Flurbiprofen (Froben) dose in adults:
Note: The lowest effective dose for the shortest possible duration should b given.
US labeling:
Flurbiprofen (Froben) dose in the treatment of Rheumatoid arthritis and osteoarthritis:
- Initial: 200 to 300 mg orally per day, divided into 2 to 4 doses.
- 100 mg as the maximum single dose (in a multiple-dose daily regimen).
Canadian labeling:
Note: The drug should be taken as soon as remembered in case of a missed dose. A single dose should be taken and the next dose skipped if the next dose is due within 2 hours.
Flurbiprofen (Froben) dose in the treatment of Ankylosing spondylitis, osteoarthritis, and rheumatoid arthritis:
- Oral: 200 mg/day in divided doses; some patients may require up to 300 mg/day during symptom exacerbations.
- The maximum dose: 300 mg/day.
Flurbiprofen (Froben) dose in Dysmenorrhea:
- Oral: 50 mg 4 times daily.
Flurbiprofen (Froben) dose in mild to moderately severe pain:
- Oral: 50 mg every 4 to 6 hours as needed.
Flurbiprofen (Froben) Use in Children:
Dose in children has not been established.
Pregnancy Risk Category: C (D in the third trimester)
- Some studies that examined in utero NSAID use revealed birth defects. However, the data is inconsistent.
- In utero NSAIDs can cause non-teratogenic effects, such as intracranial bleeding, renal failure, necrotizing collitis, and prenatal constriction.
- It is possible to see a postnatal non-closure or resection of the ductus Arteriosus that is resistant to medical treatment.
- Flurbiprofen should not be used beginning at 30 weeks of gestation because it can cause premature closure of the ductus arteriosus.
- NSAIDs may be used during pregnancy to treat mild rheumatoid-arthritis flares. However, it should be avoided or minimized in the early and later trimesters.
- Infertility can occur in women of childbearing years due to the long-term use of NSAIDs. This is reversible after withdrawal.
- The drug should not be given to women who are having trouble conceiving or are undergoing fertility treatment.
- NSAIDs used during pregnancy can increase the risk of miscarriage.
Flurbiprofen use during breastfeeding:
- Flurbiprofen can be found in breast milk.
- Flurbiprofen's relative infant dose (RID), is 0.9%. This was calculated by using the highest concentration of breast milk and compared with a 100 mg weight-adjusted maternal dosage.
- Breastfeeding can be done if the RID is less than 10%
- Breast milk has an estimated infant daily dose of 13.5 mg/kg/day. The highest milk concentration (0.09 mcg/ml) is used.
- Flurbiprofen 100mg in one dose was administered to mother and resulted in this milk concentration
- Flurbiprofen levels in breast milk reached their maximum level 3 hours after the last dose.
- Breastfeeding mothers with thrombocytopenia, deranged platelets or thrombocytopenia should not receive flurbiprofen.
- Postpartum women who want to breastfeed may use NSAIDs, but it is possible to use other agents.
- The risk of infant exposure and the benefits of breastfeeding to the baby during therapy will all play a role in deciding whether to breastfeed.
Flurbiprofen (Froben) Dose adjustment in renal disease:
-
US labeling:
-
Mild impairment:
- The labelling on products from the manufacturer does not include dose modifications;
- use with caution.
-
Moderate to severe impairment:
- The manufacturer's labelling does not mention dosage modifications, however they may be required due to potential metabolite buildup.
- Flurbiprofen should not be administered to patients with advanced renal disease unless the benefits are anticipated to outweigh the risk of decreasing renal function.
-
Continuous ambulatory peritoneal dialysis:
- Not removed by dialysis.
-
-
Canadian labeling:
-
CrCl ≥30 mL/minute or 0.5 mL/second:
- There are no dosage adjustments provided in the manufacturer's labeling; use with extreme caution.
-
CrCl <30 mL/minute or 0.5 mL/second:
- In cases of severe renal impairment (CrCl 30 mL/minute or 0.5 mL/second) or rapidly progressing renal disease, it is contraindicated.
-
Continuous ambulatory peritoneal dialysis:
- Not removed by dialysis.
-
-
KDIGO 2012 guidelines provide the following recommendations for NSAIDs:
-
eGFR 30 to <60 mL/minute/1.73 m²:
- In patients with intercurrent disease that increases risk of acute kidney injury, it should be stopped temporarily.
-
eGFR <30 mL/minute/1.73 m²:
- Avoid use.
-
Flurbiprofen (Froben) Dose adjustment in liver disease:
-
US labeling:
- Reduced doses might be necessary due to substantial hepatic metabolism; the manufacturer's labelling does not mention any dosage changes.
-
Canadian labeling:
- Usage is not advised in cases of serious liver disease or impairment.
Side Effects of Flurbiprofen (Froben):
-
Cardiovascular:
- Edema
-
Central Nervous System:
- Amnesia
- Anxiety
- Depression
- Dizziness
- Drowsiness
- Headache
- Hyperreflexia
- Insomnia
- Malaise
- Nervousness
- Vertigo
-
Dermatologic:
- Skin Rash
-
Endocrine & Metabolic:
- Weight Changes
-
Gastrointestinal:
- Abdominal Pain
- Constipation
- Diarrhea
- Dyspepsia
- Flatulence
- Gastrointestinal Bleeding
- Nausea
- Vomiting
-
Hepatic:
- Increased liver enzymes
-
Neuromuscular & skeletal:
- Tremor
- Weakness
-
Ophthalmic:
- Visual disturbance
-
Otic:
- Tinnitus
-
Respiratory:
- Rhinitis
Contraindications to Flurbiprofen (Froben):
- Hypersensitivity to any ingredient in the formulation, including flurbiprofen
- Following the use of any NSAID, including aspirin, urticaria or allergic-like responses may occur.
- Together with coronary artery bypass surgery, you can use it (CABG).
Canadian labeling: Additional contraindications not in US labeling
- Children and adolescents younger than 18 years old
- Pregnancy (last trimester),breastfeeding
- Active GI bleeding, active gastric, duodenal, and peptic ulcers
- IBD (Inflammatory Bowel Disease)
- Grave hepatic and renal impairment
- Hyperkalemia
- Uncontrolled severe heart failure
- Other bleeding disorders or cerebrovascular bleeding
Warnings and precautions
-
Anaphylactoid reactions
- Patients can develop anaphylactoid reactions even if they have not been exposed to it before.
- Patients who have rhinitis or NSAID therapy and bronchospasm are not advised to use it.
- Patients with the "aspirine triad" (bronchial aspiration, aspirin intolerance, and rhinitis) are at greater risk.
-
Cardiovascular events: [US Boxed Warn]
- NSAIDs significantly increase the risk of cardiovascular thrombotic events such as stroke and MI.
- Both the risk and the likelihood of major cardiovascular events can be increased or decreased with early treatment. Individuals who have known risk factors for cardiovascular disease are more vulnerable.
- Monitor your BP as it could lead to hypertension new-onset or exacerbation.
- NSAIDs can also cause cardiovascular events by impairing the response to ACE inhibitors, thiazide or loop diuretics.
- Patients with edema should not use it as it can cause salt or water retention.
- It should not be prescribed to patients suffering from heart disease. Patients with a recent MI should not use it unless the benefits outweigh any potential cardiovascular thrombotic events.
- To minimize cardiovascular events, it is important to use the lowest dose of medication for the shortest time. High-risk patients should consider alternate agents.
-
CNS effects
- It is possible to experience blurred vision, dizziness, drowsiness and other symptoms that can lead to impairments in physical or mental abilities.
- Patients should be warned about driving or operating machinery.
-
GI events: [US Boxed Warning]
- NSAIDs can increase the risk of serious GI inflammation, bleeding, ulceration, and even death.
- Old age, GI bleeding history and/or a history of peptic ulcer disease are all factors that increase the risk.
- These events can occur without warning and at any time during therapy.
- It should not be given to patients suffering from active GI bleeding.
- Patients with a history or tendency to have acute lower GI hemorhage should not receive non-aspirin NSAIDs, particularly if they are suffering from angioectasia and diverticulosis.
- Combination therapy can increase bleeding risk by using anticoagulants, corticosteroids and/or aspirin.
- The elderly, smokers, drinkers, people with advanced liver disease, and people with coagulopathy should stay away from the medication.
- High-risk patients should receive an alternative treatment to reduce the chance of GI complications.
- Concurrent aspirin therapy can increase the risk of GI complications, such as ulcers. Therefore, additional gastroprotective therapy (e.g., proton pump inhibitor) is recommended.
-
Genitourinary effects
- NSAID therapy can be used to treat persistent urinary symptoms such as bladder pain, dysuria and urinary frequency.
- These symptoms can occur anytime after therapy has been initiated.
- If symptoms worsen, it is best to stop taking therapy.
-
Hematologic effects
- Anemia can occur from prolonged NSAID therapy.
- Patients with coagulation disorders and those on anticoagulants need to be closely monitored for prolonged bleeding, reduced platelet adhesion, and aggregation.
- Rarely are fatal blood dyscrasias such as thrombocytopenia, anemia, and agranulocytosis.
-
Hepatic effects
- Patients with abnormal LFT should be closely monitored as it can lead to transaminitis.
- If you have symptomatic liver disease, stop all therapy immediately.
- Rarely are severe hepatic reactions such as fulminant liver disease, liver necrosis, or hepatic failure.
-
Hyperkalemia:
- It is important to monitor potassium closely as NSAIDs can increase hyperkalemia risk.
- Old age, DM, kidney disease and concomitant treatment with other agents that induce hyperkalemia (eg ACE inhibitors) are all associated with a significantly higher risk.
- Canadian labeling prohibits the use of hyperkalemia in patients.
-
Ophthalmic effects
- Blurred or diminished vision due to NSAIDs may occur. Therapy withdrawal must be completed and an ophthalmologic evaluation performed.
-
Effects on the renal system:
- NSAIDs can cause renal dysfunction by causing a decrease in renal blood flow and a dose-dependent decrease of prostaglandin synthesis.
- Patients with hypokalemia, elderly, impaired renal function, hepatic impairment and heart failure are at greater risk.
- Rehydration and monitoring of renal function are essential before starting therapy.
- Chronic NSAID therapy can be used to treat renal papillary necrosis or other injuries.
-
Reactions to skin:
- Toxic epidermal necrolysis, Stevens-Johnson syndrome, and exfoliative dermatitis (SJS) can all cause severe skin reactions that call for therapy discontinuation.
-
Aseptic meningitis
- Patients with SLE and mixed connective tissue disorders (MTC) are at greater risk for aseptic meningitis.
-
Asthma
- Patients with asthma who are sensitive to aspirin should not take it.
- Patients with other forms or asthma should be cautious.
-
Coronary bypass surgery for coronary artery bypass: [US Boxed Warn]
- Due to the increased risk of MI or stroke, it is not recommended that you use this medication in conjunction with coronary artery bypass surgery (CABG).
-
Hepatic impairment
- Due to the high hepatic metabolism, patients with hepatic diseases must reduce their doses.
- When using NSAIDs, patients with advanced liver disease are more likely to experience GI bleeding.
- Canadian labeling prohibits the use of this medication in patients with severe or active hepatic impairment.
-
Renal impairment
- Due to the possibility of metabolite accumulation, dose reduction may be necessary for patients with severe or moderate impairment.
- Patients with advanced renal disease should not be given this medication unless the benefits outweigh any potential risk to their kidney function. If therapy is required, close monitoring is essential.
- Canadian labeling prohibits the use of this medication in patients with severe kidney impairment (CrCl 30mL/minute, 0.5mL/second or deteriorating renal disease).
Flurbiprofen (systemic): Drug Interaction
|
Risk Factor C (Monitor therapy) |
|
|
5-Aminosalicylic Acid Derivatives |
Nonsteroidal Anti-Inflammatory Agents may enhance the nephrotoxic effect of 5-Aminosalicylic Acid Derivatives. |
|
Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.) |
May enhance the antiplatelet effect of other Agents with Antiplatelet Properties. |
|
Alcohol (Ethyl) |
May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Specifically, the risk of GI bleeding may be increased with this combination. |
|
Aliskiren |
Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of Aliskiren. Nonsteroidal Anti-Inflammatory Agents may enhance the nephrotoxic effect of Aliskiren. Management: Monitor renal function periodically in patients receiving aliskiren and any nonsteroidal anti-inflammatory agent. Patients at elevated risk of renal dysfunction include those who are elderly, are volume depleted, or have pre-existing renal dysfunction. |
|
Aminoglycosides |
Nonsteroidal Anti-Inflammatory Agents may decrease the excretion of Aminoglycosides. Data only in premature infants. |
|
Aminolevulinic Acid (Topical) |
Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Topical). |
|
Angiotensin II Receptor Blockers |
May enhance the adverse/toxic effect of Nonsteroidal AntiInflammatory Agents. Specifically, the combination may result in a significant decrease in renal function. Nonsteroidal Anti-Inflammatory Agents may diminish the therapeutic effect of Angiotensin II Receptor Blockers. The combination of these two agents may also significantly decrease glomerular filtration and renal function. |
|
Angiotensin-Converting Enzyme Inhibitors |
May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Specifically, the combination may result in a significant decrease in renal function. Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of Angiotensin-Converting Enzyme Inhibitors. |
|
Anticoagulants |
Agents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants. |
|
Anticoagulants |
Nonsteroidal Anti-Inflammatory Agents may enhance the anticoagulant effect of Anticoagulants. |
|
Beta-Blockers |
Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of Beta-Blockers. Exceptions: Levobunolol; Metipranolol. |
|
Bisphosphonate Derivatives |
Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Bisphosphonate Derivatives. Both an increased risk of gastrointestinal ulceration and an increased risk of nephrotoxicity are of concern. |
|
Cephalothin |
Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Cephalothin. Specifically, the risk for bleeding may be increased. |
|
Collagenase (Systemic) |
Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Collagenase (Systemic). Specifically, the risk of injection site bruising and/or bleeding may be increased. |
|
Corticosteroids (Systemic) |
May enhance the adverse/toxic effect of Nonsteroidal AntiInflammatory Agents (Nonselective). |
|
Dasatinib |
May enhance the anticoagulant effect of Agents with Antiplatelet Properties. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. |
|
Deferasirox |
Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Deferasirox. Specifically, the risk for GI ulceration/irritation or GI bleeding may be increased. |
|
Deoxycholic Acid |
Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Deoxycholic Acid. Specifically, the risk for bleeding or bruising in the treatment area may be increased. |
|
Desmopressin |
Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Desmopressin. |
|
Digoxin |
Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Digoxin. |
|
Drospirenone |
Nonsteroidal Anti-Inflammatory Agents may enhance the hyperkalemic effect of Drospirenone. |
|
Eplerenone |
Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of Eplerenone. Nonsteroidal Anti-Inflammatory Agents may enhance the hyperkalemic effect of Eplerenone. |
|
Fat Emulsion (Fish Oil Based) |
May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. |
|
Felbinac |
May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. |
|
Glucosamine |
May enhance the antiplatelet effect of Agents with Antiplatelet Properties. |
|
Haloperidol |
Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Haloperidol. Specifically including drowsiness and confusion. |
|
HydrALAZINE |
Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of HydrALAZINE. |
|
Ibritumomab Tiuxetan |
Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Ibritumomab Tiuxetan. Both agents may contribute to impaired platelet function and an increased risk of bleeding. |
|
Ibrutinib |
May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. |
|
Inotersen |
May enhance the antiplatelet effect of Agents with Antiplatelet Properties. |
|
Limaprost |
May enhance the antiplatelet effect of Agents with Antiplatelet Properties. |
|
Multivitamins/Fluoride (with ADE) |
May enhance the antiplatelet effect of Agents with Antiplatelet Properties. |
|
Multivitamins/Minerals (with ADEK, Folate, Iron) |
May enhance the antiplatelet effect of Agents with Antiplatelet Properties. |
|
Multivitamins/Minerals (with AE, No Iron) |
May enhance the antiplatelet effect of Agents with Antiplatelet Properties. |
|
Naftazone |
May enhance the antiplatelet effect of Nonsteroidal Anti-Inflammatory Agents. |
|
Obinutuzumab |
Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Obinutuzumab. Specifically, the risk of serious bleeding-related events may be increased. |
|
Omega-3 Fatty Acids |
May enhance the antiplatelet effect of Agents with Antiplatelet Properties. |
|
Pentosan Polysulfate Sodium |
May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Specifically, the risk of bleeding may be increased by concurrent use of these agents. |
|
Pentoxifylline |
May enhance the antiplatelet effect of Agents with Antiplatelet Properties. |
|
Porfimer |
Photosensitizing Agents may enhance the photosensitizing effect of Porfimer. |
|
Potassium-Sparing Diuretics |
Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of Potassium-Sparing Diuretics. Nonsteroidal Anti-Inflammatory Agents may enhance the hyperkalemic effect of Potassium-Sparing Diuretics. |
|
PRALAtrexate |
Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of PRALAtrexate. More specifically, NSAIDS may decrease the renal excretion of pralatrexate. Management: Closely monitor for increased pralatrexate serum levels and/or toxicity if used concomitantly with an NSAID. Monitor for decreased pralatrexate serum levels with NSAID discontinuation. |
|
Probenecid |
May increase the serum concentration of Nonsteroidal Anti-Inflammatory Agents. |
|
Prostacyclin Analogues |
May enhance the antiplatelet effect of Agents with Antiplatelet Properties. |
|
Prostaglandins (Ophthalmic) |
Nonsteroidal Anti-Inflammatory Agents may diminish the therapeutic effect of Prostaglandins (Ophthalmic). Nonsteroidal Anti-Inflammatory Agents may also enhance the therapeutic effects of Prostaglandins (Ophthalmic). |
|
Quinolones |
Nonsteroidal Anti-Inflammatory Agents may enhance the neuroexcitatory and/or seizure-potentiating effect of Quinolones. Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Quinolones. |
|
Salicylates |
Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Salicylates. Increased risk of bleeding may result. |
|
Serotonin/Norepinephrine Reuptake Inhibitors |
May enhance the antiplatelet effect of Nonsteroidal Anti-Inflammatory Agents (Nonselective). |
|
Tacrolimus (Systemic) |
Nonsteroidal Anti-Inflammatory Agents may enhance the nephrotoxic effect of Tacrolimus (Systemic). |
|
Thiazide and Thiazide-Like Diuretics |
May enhance the nephrotoxic effect of Nonsteroidal AntiInflammatory Agents. Nonsteroidal Anti-Inflammatory Agents may diminish the therapeutic effect of Thiazide and Thiazide-Like Diuretics. |
|
Thrombolytic Agents |
Agents with Antiplatelet Properties may enhance the anticoagulant effect of Thrombolytic Agents. |
|
Tipranavir |
May enhance the antiplatelet effect of Agents with Antiplatelet Properties. |
|
Tolperisone |
Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Tolperisone. Specifically, the risk of hypersensitivity reactions may be increased. Tolperisone may enhance the therapeutic effect of Nonsteroidal Anti-Inflammatory Agents. |
|
Tricyclic Antidepressants (Tertiary Amine) |
May enhance the antiplatelet effect of Nonsteroidal Anti-Inflammatory Agents (Nonselective). |
|
Vancomycin |
Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Vancomycin. |
|
Verteporfin |
Photosensitizing Agents may enhance the photosensitizing effect of Verteporfin. |
|
Vitamin E (Systemic) |
May enhance the antiplatelet effect of Agents with Antiplatelet Properties. |
|
Risk Factor D (Consider therapy modification) |
|
|
Apixaban |
Nonsteroidal Anti-Inflammatory Agents (Nonselective) may enhance the adverse/toxic effect of Apixaban. Specifically, the risk of bleeding may be increased. Management: A comprehensive risk to benefit assessment should be done for all patients before any concurrent use of apixaban and nonsteroidal anti-inflammatory drugs (NSAIDs). If combined, monitor patients extra closely for signs and symptoms of bleeding. |
|
Bile Acid Sequestrants |
May decrease the absorption of Nonsteroidal Anti-Inflammatory Agents. |
|
CycloSPORINE (Systemic) |
Nonsteroidal Anti-Inflammatory Agents may enhance the nephrotoxic effect of CycloSPORINE (Systemic). CycloSPORINE (Systemic) may increase the serum concentration of Nonsteroidal Anti-Inflammatory Agents. Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of CycloSPORINE (Systemic). Management: Consider alternatives to nonsteroidal anti-inflammatory agents (NSAIDs). Monitor for evidence of nephrotoxicity, as well as increased serum cyclosporine concentrations and systemic effects (eg, hypertension) during concomitant therapy with NSAIDs. |
|
Dabigatran Etexilate |
Nonsteroidal Anti-Inflammatory Agents (Nonselective) may enhance the adverse/toxic effect of Dabigatran Etexilate. Specifically, the risk of bleeding may be increased. Management: A comprehensive risk to benefit assessment should be done for all patients before any concurrent use of dabigatran and nonsteroidal anti-inflammatory drugs (NSAIDs). If combined, monitor patients extra closely for signs and symptoms of bleeding. |
|
Diclofenac (Systemic) |
May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Management: Seek alternatives to the combined use of diclofenac with other nonsteroidal anti-inflammatory agents (NSAIDs). Avoid the use of diclofenac/misoprostol with other NSAIDs. |
|
Edoxaban |
Nonsteroidal Anti-Inflammatory Agents (Nonselective) may enhance the adverse/toxic effect of Edoxaban. Specifically, the risk of bleeding may be increased. Management: A comprehensive risk to benefit assessment should be done for all patients before any concurrent use of edoxaban and nonsteroidal anti-inflammatory drugs (NSAIDs). If combined, monitor patients extra closely for signs and symptoms of bleeding. |
|
Herbs (Anticoagulant/Antiplatelet Properties) (eg, Alfalfa, Anise, Bilberry) |
May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Bleeding may occur. Management: Avoid combination when possible. If used, monitor more closely for evidence of bleeding. Discontinue herbal products with anticoagulant or antiplatelet actions 2 weeks prior to surgical, dental, or invasive procedures. |
|
Herbs (Anticoagulant/Antiplatelet Properties) (eg, Alfalfa, Anise, Bilberry) |
May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Bleeding may occur. Management: Concomitant treatment with these agents should generally be avoided. If used concomitantly, increased diligence in monitoring for adverse effects (eg, bleeding, bruising, altered mental status due to CNS bleeds) must be employed. |
|
Lithium |
Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Lithium. |
|
Loop Diuretics |
Nonsteroidal Anti-Inflammatory Agents may diminish the diuretic effect of Loop Diuretics. Loop Diuretics may enhance the nephrotoxic effect of Nonsteroidal Anti-Inflammatory Agents. Management: Monitor for evidence of kidney injury or decreased therapeutic effects of loop diuretics with concurrent use of an NSAID. Consider avoiding concurrent use in CHF or cirrhosis. Concomitant use of bumetanide with indomethacin is not recommended. |
|
Methotrexate |
Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Methotrexate. Management: Alternative anti-inflammatory therapy should be considered whenever possible, especially if the patient is receiving higher, antineoplastic doses of methotrexate. |
|
Rivaroxaban |
Nonsteroidal Anti-Inflammatory Agents (Nonselective) may enhance the adverse/toxic effect of Rivaroxaban. Specifically, the risk of bleeding may be increased. Management: A comprehensive risk to benefit assessment should be done for all patients before any concurrent use of rivaroxaban and nonsteroidal anti-inflammatory drugs (NSAIDs). If combined, monitor patients extra closely for signs and symptoms of bleeding. |
|
Salicylates |
Nonsteroidal Anti-Inflammatory Agents (Nonselective) may enhance the adverse/toxic effect of Salicylates. An increased risk of bleeding may be associated with use of this combination. Nonsteroidal Anti-Inflammatory Agents (Nonselective) may diminish the cardioprotective effect of Salicylates. Salicylates may decrease the serum concentration of Nonsteroidal Anti-Inflammatory Agents (Nonselective). Exceptions: Choline Magnesium Trisalicylate. |
|
Selective Serotonin Reuptake Inhibitors |
May enhance the antiplatelet effect of Nonsteroidal Anti-Inflammatory Agents (Nonselective). Nonsteroidal Anti-Inflammatory Agents (Nonselective) may diminish the therapeutic effect of Selective Serotonin Reuptake Inhibitors. Management: Consider using alternative analgesics, when appropriate, and/or addition of a gastroprotective agent. Monitor patients closely for signs/symptoms of bleeding, and for evidence of diminished SSRI effectiveness with concurrent use. |
|
Sincalide |
Drugs that Affect Gallbladder Function may diminish the therapeutic effect of Sincalide. Management: Consider discontinuing drugs that may affect gallbladder motility prior to the use of sincalide to stimulate gallbladder contraction. |
|
Sodium Phosphates |
May enhance the nephrotoxic effect of Nonsteroidal Anti-Inflammatory Agents. Specifically, the risk of acute phosphate nephropathy may be enhanced. Management: Consider avoiding this combination by temporarily suspending treatment with NSAIDs, or seeking alternatives to oral sodium phosphate bowel preparation. If the combination cannot be avoided, maintain adequate hydration and monitor renal function closely. |
|
Tenofovir Products |
Nonsteroidal Anti-Inflammatory Agents may enhance the nephrotoxic effect of Tenofovir Products. Management: Seek alternatives to these combinations whenever possible. Avoid use of tenofovir with multiple NSAIDs or any NSAID given at a high dose. |
|
Vitamin K Antagonists (eg, warfarin) |
Nonsteroidal Anti-Inflammatory Agents (Nonselective) may enhance the anticoagulant effect of Vitamin K Antagonists. |
|
Risk Factor X (Avoid combination) |
|
|
Acemetacin |
May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. |
|
Aminolevulinic Acid (Systemic) |
Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Systemic). |
|
Dexibuprofen |
Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Dexibuprofen. |
|
Dexketoprofen |
May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. |
|
Floctafenine |
May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. |
|
Ketorolac (Nasal) |
May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. |
|
Ketorolac (Systemic) |
May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. |
|
Macimorelin |
Nonsteroidal Anti-Inflammatory Agents may diminish the diagnostic effect of Macimorelin. |
|
Mifamurtide |
Nonsteroidal Anti-Inflammatory Agents may diminish the therapeutic effect of Mifamurtide. |
|
Morniflumate |
May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. |
|
Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective) |
Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective). |
|
Omacetaxine |
Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Omacetaxine. Specifically, the risk for bleeding-related events may be increased. Management: Avoid concurrent use of nonsteroidal anti-inflammatory drugs (NSAIDs) with omacetaxine in patients with a platelet count of less than 50,000/uL. |
|
Pelubiprofen |
May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. |
|
Phenylbutazone |
May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. |
|
Talniflumate |
May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. |
|
Tenoxicam |
May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. |
|
Urokinase |
Agents with Antiplatelet Properties may enhance the anticoagulant effect of Urokinase. |
|
Zaltoprofen |
May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. |
Monitoring parameters:
- BP
- CBC
- LFTs
- RFTs (urine output, serum BUN and creatinine)
- chemistry profile
- signs or symptoms of GI bleeding
- Occult blood loss
- periodic ophthalmologic exam with chronic use
How to administer Flurbiprofen (Froben)?
- It can be given orally with food, milk, or antacids.
- Canadian labeling recommends taking immediately after a meal or with food or milk.
Mechanism of action of Flurbiprofen (Froben):
- Flurbiprofen has anti-inflammatory, analgesic and antipyretic properties.
- It reduces the formation of prostaglandin precursors through reversible inhibitions of cyclooxygenase-1 (COX-1) and 2 enzymes.
- Chemotaxis inhibition, altered lymphocyte activity, lowered proinflammatory cytokine levels, and other hypothesised mechanisms that have not yet been fully explained may also contribute to the anti-inflammatory impact to variable degrees.
Absorption:
- Rapid
Protein binding:
- >99%, primarily albumin
Metabolism:
- Hepatic via CYP2C9; major metabolite is 4-hydroxy-flurbiprofen (inactive)
Bioavailability:
- 96%
Half-life elimination:
- 4.7 to 5.7 hours
Time to peak:
- ~2 hours
Excretion:
- Urine (<3% as unchanged; ~70% primarily as metabolites)
International Brands of Flurbiprofen:
- NOVO-Flurprofen SR
- TEVA-Flurbiprofen
- Anflupin
- Ansaid
- Antadys
- Arflur
- Bifen Cataplasma
- Cebutid
- Clinadol Forte
- Distex
- Eyefen
- Flugalin
- Flurbi
- Flurbic
- Flurofen
- Flurofen Retard
- Flurozin
- Froben
- Froben SR
- Lefenine
- Luarprofeno
- Majezik
- Nibelon
- Penostop
- Ropion
- Strefen
- Strepfen
- Strepsils
- Strepsils Intensiv
- Strepsils Intensive
- Urbifen
Flurbiprofen Brand Names in Pakistan:
Flurbiprofen Eye Drops 0.03 % w/v |
|
| Enflam | Tg Pharma |
| Eyeflox | P.D.H. Pharmaceuticals (Pvt) Ltd. |
| Feny | Kobec Pharmacals |
| Ocufen | Barrett Hodgson Pakistan (Pvt) Ltd. |
| Optiprofen | P.D.H. Pharmaceuticals (Pvt) Ltd. |
| Optofen | Sante (Pvt) Limited |
Flurbiprofen Gel 5 % w/w |
|
| Fenpro | Safina Pharma (Pvt) Ltd |
| Froben | Abbott Laboratories (Pakistan) Limited. |
| Froben | Abbott Laboratories (Pakistan) Limited. |
| Parofen | Syntex Pharmaceuticals |
| Pro-F | Opal Laboratories (Pvt) Ltd. |
| Relaxofen | Epharm Laboratories |
Flurbiprofen 50 mg Tablets |
|
| Biprofin | Martin Dow Pharmaceuticals (Pak) Ltd. |
| Biprotec | Jafson Pharmaceuticals (Pvt) Ltd. |
| Endol | Paramount Pharmaceuticals |
| Fbi | Medicraft Pharmaceuticals (Pvt) Ltd. |
| Flamtab | Semos Pharmaceuticals (Pvt) Ltd. |
| Flasic | Roomi Enterprises (Pvt) Ltd |
| Floriwel | Welmark Pharmaceuticals |
| Flurbin | Mass Pharma (Private) Limited |
| Flurbizan | Medizan Labs (Pvt) Ltd |
| Flurip | Askari Pharmaceuticals. |
| Flurofen | Polyfine Chempharma (Pvt) Ltd. |
| Flurwin | Wns Field Pharmaceuticals |
| Froben | Abbott Laboratories (Pakistan) Limited. |
| Lubifen | Pharmacare Laboratories (Pvt) Ltd. |
| Rangafen | Hygeia Pharmaceuticals |
| Rumagesic | Euro Pharma International |
| Urbofen | Valor Pharmaceuticals |
Flurbiprofen 100 mg Tablets |
|
| Adwin | Bloom Pharmaceuticals (Pvt) Ltd. |
| Anaf | Vega Pharmaceuticals Ltd. |
| Anorcid | Adamjee Pharmaceuticals (Pvt) Ltd. |
| Ansaid | Pfizer Laboratories Ltd. |
| Arbiprofen | Arsons Pharmaceuticals Industries (Pvt) Ltd |
| Arthrofen | Nabiqasim Industries (Pvt) Ltd. |
| Askosaid | Ideal Pharmaceutical Industries |
| Balp | Isis Pharmaceutical |
| Benprofen | Benson Pharamceuticals. |
| Biake | Evergreen Pharmaceuticals Pvt Limited |
| Biprofin | Martin Dow Pharmaceuticals (Pak) Ltd. |
| Biprogesic | Zinta Pharmaceuticals Industries |
| Bro-Z | Z-Jans Pharmaceutical (Pvt) Ltd. |
| Brufoz | Fozan Pharmaceuticals Industriers (Pvt) Ltd |
| Dansaid | Danas Pharmaceuticals (Pvt) Ltd |
| Dentifen | Macter International (Pvt) Ltd. |
| Dol | Wilshire Laboratories (Pvt) Ltd. |
| Dolorid | Maple Pharmaceuticals (Pvt) Ltd |
| Dulpro | Global Pharmaceuticals |
| Edge | W & Ali Sons Pharmaceuticals |
| Elient | Gray`S Pharmaceuticals |
| Endol | Paramount Pharmaceuticals |
| Exflam | Tg Pharma |
| F-100 | English Pharmaceuticals Industries |
| Fabofen | Bloom Pharmaceuticals (Pvt) Ltd. |
| Fabrul | Focus & Rulz Pharmaceuticals |
| Fb-Said | Alkemy Pharmaceutical Laboratories (Private) Ltd. |
| Fbi | Medicraft Pharmaceuticals (Pvt) Ltd. |
| Febagyl | Noa Hemis Pharmaceuticals |
| Fen-100 | Nenza Pharmaceuticals (Pvt) Limited |
| Fenpro | Safina Pharma (Pvt) Ltd |
| Ferryfen | Florence Farmaceuticals (Pvt) Ltd |
| Flamtab | Semos Pharmaceuticals (Pvt) Ltd. |
| Flasic | Roomi Enterprises (Pvt) Ltd |
| Flip | Zephyr Pharmatec (Pvt) Ltd. |
| Flog | Rogen Pharmaceuticals |
| Florip | Goodman Laboratories |
| Floriwel | Welmark Pharmaceuticals |
| Flubi | Al-Habib Pharmaceuticals. |
| Fluoral | Alson Pharmaceuticals |
| Flur | Epoch Pharmaceutical |
| Flurant | Amarant Pharmaceuticals (Pvt) |
| Flurbiadvan | Advanced Pharmaceuticals |
| Flurbimak | Makson Pharmaceuticals |
| Flurbin | Mass Pharma (Private) Limited |
| Flurbizan | Medizan Labs (Pvt) Ltd |
| Flurfin | Nova Med Pharmaceuticals |
| Flurgem | Delux Chemical Industries |
| Fluridol | Envoy Pharma |
| Flurip | Askari Pharmaceuticals. |
| Fluritab | Lahore Chemical & Pharmaceutical Works (Pvt) Ltd |
| Fluritab-100 | Nova Med Pharmaceuticals |
| Flurle | Leads Pharma (Pvt) Ltd |
| Flurofen | Medisure Laboratories Pakistan (Pvt.) Ltd. |
| Flursaid | Friends Pharma (Pvt) Ltd |
| Flurun | Qintar Pharmacuticals |
| Flurwin | Wns Field Pharmaceuticals |
| Flurwood | W.Woodward Pakistan (Pvt) Ltd. |
| Flusaid | Alliance Pharmaceuticals (Pvt) Ltd. |
| Flusid | Batala Pharmaceuticals. |
| Fluwitt | Lowitt Pharmaceuticals (Pvt) Ltd |
| Frobafen | Caylex Pharmaceuticals (Pvt) Ltd. |
| Froben | Abbott Laboratories (Pakistan) Limited. |
| Frodon | Saydon Pharmaceutical Industries (Pvt) Ltd. |
| Frogesic | Navegal Laboratories |
| Frugesic | Mediceena Pharma (Pvt) Ltd. |
| Fufit | Wise Pharmaceuticals (Pvt) Ltd |
| Fysid | Fynk Pharmaceuticals |
| Getnov | Nova Med Pharmaceuticals |
| Glofen | Webros Pharmaceuticals |
| Hafsad | Zesion Pharmaceutical (Pvt) Ltd |
| Harisid | Harrison Pharmaceuticals |
| Healsed | Heal Pharmaceuticals Pvt Ltd |
| Ib-Proof | Jinnah Pharmaceuticals |
| Inflamatix | Continental Chemical Company (Pvt) Ltd. |
| Inovan | Raazee Theraputics (Pvt) Ltd. |
| Instagesic | Azron Pharmaceuticals (Pvt) Ltd |
| Jasic | Libra Pharmaceuticals (Pvt) Ltd |
| Kolzin | Spirax International |
| Lorbi | Fedro Pharmaceutical |
| Magifen | Dr. Raza Pharma (Private) Limited |
| Marifen | Miracle Pharmaceuticals(Pvt) Ltd |
| Mobez | Figs Pharmaceuticals |
| Naplur | Munawar Pharma (Pvt) Ltd. |
| Nefro | P.D.H. Pharmaceuticals (Pvt) Ltd. |
| Neo Triad | Helicon Pharmaceutek Pakistan (Pvt) Ltd. |
| Nu-Flurbrofen | Hamaz Pharmaceutical (Pvt) Ltd. |
| Olgon | Himont Pharmaceuticals (Pvt) Ltd. |
| Oragesic | Himont Pharmaceuticals (Pvt) Ltd. |
| Ostiflur | Medisure Laboratories Pakistan (Pvt.) Ltd. |
| Paincid | Schazoo Zaka |
| Pansaid | Pakheim Internanational Pharma |
| Pansol | Pharmix Laboratories (Private) Limited. |
| Parad | Silver Oak Corporation. |
| Parofen | Syntex Pharmaceuticals |
| Pictor | Max Pharmaceuticals |
| Pictor | Max Pharmaceuticals |
| Pro-F | Opal Laboratories (Pvt) Ltd. |
| Puricap | Rotex Medica Pakistan (Pvt) Ltd |
| Q-Fur | Epoch Pharmaceutical |
| Rakaprofen | Rakaposhi Pharmaceutical (Pvt) Ltd. |
| Rangafen | Hygeia Pharmaceuticals |
| Rasbid | Rasco Pharma |
| Relaxofen | Epharm Laboratories |
| Relaxofen | Epharm Laboratories |
| Relepan | Lloyds Pharmaceuticals |
| Riboprofen | Ferroza International Pharmaceuticals (Pvt) Ltd. |
| Robigesic | Robins Pharmaceutical Industries |
| Rubinol | Obsons Pharmaceuticals |
| Rubio | Nimrall Laboratories |
| Rumagesic | Euro Pharma International |
| Sanid | Stanley Pharmaceuticals (Pvt) Ltd. |
| Sapid | Sapient Pharma |
| Siskat | Tagma Pharma (Pvt) Ltd. |
| Skel Fen | Pakistan Pharmaceutical Products (Pvt) Ltd. |
| Strefen | Healers Laboratories |
| Swaprofen | Swan Pharmaceuticals(Pvt) Ltd |
| Synalgo | Platinum Pharmaceuticals (Pvt.) Ltd. |
| Syro | Albro Pharma |
| Taprofen | Jawa Pharmaceuticals(Pvt) Ltd. |
| Tencid | Regent Laboratories Ltd. |
| Tornil | Serene Pharmaceuticals |
| Ultifen | Hansel Pharmacueutical Pvt (Ltd) |
| Urben | Zanctok Pharmaceuticals |
| Urbicid | Flow Pharmaceuticals (Pvt) Ltd. |
| Urbofen | Valor Pharmaceuticals |
| Velsaid | Everest Pharmaceuticals |
| Vio Fen | Venus Pharma |
| Vio Fen | Venus Pharma |
| Viosaid | Venus Pharma |
| Vobifen | Novartis Pharma (Pak) Ltd |
| Zitis | Excel Healthcare Laboratories (Pvt.) Ltd. |
Flurbiprofen 200 mg Tablets |
|
| Swaprofen | Swan Pharmaceuticals(Pvt) Ltd |
Flurbiprofen SR 200 mg Tablets |
|
| Inovan | Raazee Theraputics (Pvt) Ltd. |
Flurbiprofen 100 mg Capsules |
|
| Florefen | Florence Farmaceuticals (Pvt) Ltd |
Flurbiprofen Capsules SR 200 mg |
|
| Froben | Abbott Laboratories (Pakistan) Limited. |
