Flurbiprofen

Flurbiprofen is Non- Steroidal Anti inflammatory Drugs belonging to Analgesic and Anti inflammatory agents.

Flurbiprofen is used in the treatment of osteoarthritis, rheumatoid arthritis, Ankylosing spondylitis; Dysmenorrhea; Pain

Flurbiprofen is Rapidly absorbed from the gastrointestinal tract. Decreased absorption rate with food. Bioavailability: 96% (oral). Time to peak plasma concentration: Approx 2 hours (oral). It is present in breast milk (small amount) with volume of distribution of about 0.12 L/kg. Plasma protein-binding: >99%, mainly to albumin and get Metabolised in the liver by hydroxylation (via CYP2C9 isoenzyme) and conjugation and get excreted via urine (<3% as unchanged drug; approx 70% mainly as metabolites). Elimination half-life: 4.7-5.7 hours.

The common side effects of Flurbiprofen includes Renal papillary necrosis (prolonged use), anaphylactoid reactions, blood dyscrasias (e.g. agranulocytosis, thrombocytopenia, aplastic anaemia), hyperkalaemia.

Flurbiprofen is available in Tablet.

Flurbiprofen is available in India, Germany, Canada, France, USA.

Reversibly inhibits cyclooxygenase-1 and 2 (COX-1 and 2) enzymes, which results in decreased formation of prostaglandin precursors; has antipyretic, analgesic, and anti-inflammatory properties.

Flurbiprofen is available in the form of tablets.

Flurbiprofen is used in the treatment of osteoarthritis, rheumatoid arthritis, Ankylosing spondylitis; Dysmenorrhea; Pain.

Flurbiprofen, a propionic acid derivative, is an NSAID that reversibly inhibits cyclooxygenase-1 and 2 (COX-1 and 2) enzymes, resulting in decreased formation of prostaglandin precursors. It has antipyretic, anti-inflammatory and analgesic properties.

Flurbiprofen is approved for use in the following clinical indications

Osteoarthritis, rheumatoid arthritis: Relief of the signs and symptoms of osteoarthritis and rheumatoid arthritis.

• Although not approved there have been certain off labelled uses documented for Flurbiprofen which includes:

Ankylosing spondylitis; Dysmenorrhea; Pain.

• Acute pain (off label): Oral: 150 to 300 mg/day in 3 to 4 divided doses as needed.
• Ankylosing spondylitis (off label): Oral: 50 mg 2 to 4 times daily; some patients may require up to 300 mg/day during symptom.
• Dysmenorrhea (off label): Oral: 50 mg 4 times daily.
• Osteoarthritis: Oral: Initial: 200 to 300 mg/day in 2 to 4 divided doses; maximum: 100 mg/dose.
• Rheumatoid arthritis: Oral: Initial: 200 to 300 mg/day in 2 to 4 divided doses; maximum: 100 mg/dose.

Flurbiprofen is available in the dosage strength of 50 mg and 100 mg.

Flurbiprofen is available in the form of Tablets.

• Dosage Adjustment in Kidney Patient

eGFR 30 to <60 mL/minute/1.73 m²: Temporarily discontinue in patients with intercurrent disease that increases risk of acute kidney injury.

eGFR <30 mL/minute/1.73 m²: Avoid use.

Hypersensitivity to flurbiprofen, aspirin or other NSAIDs. History of gastrointestinal bleeding or perforation related to NSAID therapy. Active or history of gastrointestinal inflammatory disease (e.g. ulcerative colitis, Crohn’s disease), ulceration, or haemorrhage, aspirin-sensitive asthma, severe heart failure, treatment of pain in the setting of CABG. Patients with epithelial herpes simplex keratitis, known haemostatic defects, or those receiving other drugs which may prolong bleeding time (ophthalmic). Avoid ophthalmic use during surgical procedures. Severe renal and hepatic impairment. Pregnancy (3rd trimester).

Concerns related to adverse effects:

• Anaphylactoid reactions: Even in patients without prior exposure, anaphylactoid reactions may occur; patients with "aspirin triad" (bronchial asthma, aspirin intolerance, rhinitis) may be at increased risk. Contraindicated in patients who experience bronchospasm, asthma, rhinitis, or urticaria with nonsteroidal anti-inflammatory drug (NSAID) or aspirin therapy.

• Cardiovascular events: Relative risk of serious adverse cardiovascular thrombotic events appears to be similar in those with and without known cardiovascular disease or risk factors for cardiovascular disease; however, absolute incidence of serious cardiovascular thrombotic events (which may occur early during treatment) was higher in patients with known cardiovascular disease or risk factors. New-onset hypertension or exacerbation of hypertension may occur (NSAIDs may also impair response to angiotensin-converting enzyme [ACE] inhibitors, thiazide diuretics, or loop diuretics); may contribute to cardiovascular events; monitor blood pressure; use with caution in patients with hypertension. May cause sodium and fluid retention; use with caution in patients with edema. Avoid use in heart failure. Avoid use in patients with a recent myocardial infarction (MI) unless benefits outweigh risk of cardiovascular thrombotic events. Use the lowest effective dose for the shortest duration of time, consistent with individual patient goals, to reduce risk of cardiovascular events; alternate therapies should be considered for patients at high risk.

• CNS effects: May cause drowsiness, dizziness, blurred vision, and other neurologic effects which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery or driving).

• Drug reaction with eosinophilia and systemic symptoms: Potentially serious, sometimes fatal, drug reaction with eosinophilia and systemic symptoms (DRESS), also known as multiorgan hypersensitivity reactions, has been reported with NSAIDs. Monitor for signs and symptoms (eg, fever, rash, lymphadenopathy, eosinophilia) in association with other organ system involvement (eg, hepatitis, nephritis, hematological abnormalities, myocarditis, myositis). Early symptoms of hypersensitivity reaction (eg, lymphadenopathy, fever) may occur without rash; discontinue therapy and further evaluate if DRESS is suspected.

• GI events: Avoid use in patients with active GI bleeding due to increased risk of serious GI events. In patients with a history of acute lower gastrointestinal bleeding, avoid use of non-aspirin NSAIDs, especially if due to angioectasia or diverticulosis. Use caution with a history of GI ulcers, concurrent therapy known to increase the risk of GI bleeding (eg, aspirin, anticoagulants and/or corticosteroids, selective serotonin reuptake inhibitors), advanced hepatic disease, coagulopathy, smoking, use of alcohol, or in the elderly, or debilitated patients. Use the lowest effective dose for the shortest duration of time, consistent with individual patient goals, to reduce risk of GI adverse events; alternate therapies should be considered for patients at high risk. When used concomitantly with aspirin, a substantial increase in the risk of GI complications (eg, ulcer) occurs; concomitant gastroprotective therapy (eg, proton pump inhibitors) is recommended.

• Genitourinary effects: NSAIDs may be associated with persistent urinary symptoms (bladder pain, dysuria, urinary frequency), hematuria, or cystitis. The onset of these symptoms may occur at any time after the initiation of therapy. Some cases have become severe on continued treatment; discontinue therapy to ascertain if symptoms disappear.

• Hematologic effects: Platelet adhesion and aggregation may be decreased; may prolong bleeding time; patients with coagulation disorders or who are receiving anticoagulants should be monitored closely. Anemia may occur; patients on long-term NSAID therapy should be monitored for anemia. Rarely, NSAID use has been associated with potentially severe blood dyscrasias (eg, agranulocytosis, thrombocytopenia, aplastic anemia).

• Hepatic effects: Transaminase elevations have been reported with use; closely monitor patients with any abnormal LFT. Rare (sometimes fatal) severe hepatic reactions (eg, fulminant hepatitis, liver necrosis, hepatic failure) have occurred with NSAID use; discontinue immediately if signs or symptoms of hepatic disease develop or if systemic manifestations occur.

• Hyperkalemia: NSAID use may increase the risk of hyperkalemia, particularly in the elderly, diabetics, renal disease, and with concomitant use of other agents capable of inducing hyperkalemia (eg, ACE inhibitors). Monitor potassium closely.

• Ophthalmic effects: Blurred and/or diminished vision has been reported; discontinue use and refer for ophthalmologic evaluation if such symptoms occur.

• Renal effects: NSAID use may compromise existing renal function; dose-dependent decreases in prostaglandin synthesis may result from NSAID use, reducing renal blood flow which may cause renal decompensation (usually reversible). Patients with impaired renal function, dehydration, hypovolemia, heart failure, hepatic impairment, those taking diuretics, and ACE inhibitors, and the elderly are at greater risk of renal toxicity. Rehydrate patient before starting therapy; monitor renal function closely. Long-term NSAID use may result in renal papillary necrosis and other renal injury.

• Skin reactions: NSAIDs may cause potentially fatal serious skin adverse events including exfoliative dermatitis, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN); may occur without warning; discontinue use at first sign of skin rash (or any other hypersensitivity).

Flurbiprofen may cause liver problems, and using it with substantial quantities of ethanol may increase that risk.

Rate and extent of absorption may be reduced when taken with food or milk. Increased risk of gastrointestinal bleeding with alcohol.

• Common Adverse effects:

Renal papillary necrosis (prolonged use), anaphylactoid reactions, blood dyscrasias (e.g. agranulocytosis, thrombocytopenia, aplastic anemia), hyperkaliemia.

• Less Common Adverse effects:

Nausea, vomiting, diarrhea, dyspepsia, flatulence, constipation, abdominal pain, melaena, hematemesis, ulcerative stomatitis, gastritis. Lozenge/throat spray: Throat irritation, mouth ulceration, oral pain or discomfort, oral paresthesia, oropharyngeal pain

• Rare Adverse effects

Hepatotoxicity (e.g. fulminant hepatitis, hepatic necrosis, hepatic failure), exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis.

Decreased effect of diuretics, ACE inhibitors, angiotensin II antagonists, and mifepristone. Increased plasma concentration and risk of toxicity of lithium, cardiac glycosides (e.g. digoxin), phenytoin and methotrexate. Enhanced anticoagulant effect of warfarin. Increased risk of nephrotoxicity with ciclosporin, tacrolimus and diuretics. Increased risk of gastrointestinal ulceration or bleeding with other NSAIDs, corticosteroids, SSRIs, and anticoagulants or antiplatelet agents (e.g. aspirin). Increased haematological toxicity with zidovudine.

The common side effects of Flurbiprofen include the following :

Renal papillary necrosis (prolonged use), anaphylactoid reactions, blood dyscrasias (e.g. agranulocytosis, thrombocytopenia, aplastic anaemia), hyperkalaemia.

Symptoms: Lethargy, drowsiness, nausea, vomiting, epigastric pain, gastrointestinal bleeding. Rarely, hypertension, acute renal failure, respiratory depression, coma.

Management: Supportive and symptomatic treatment. Consider emesis, activated charcoal, and/or osmotic catharsis within 4 hours of ingestion or in case of large overdosage.

• Pharmacodynamic

Flurbiprofen, a propionic acid derivative, is an NSAID that reversibly inhibits cyclooxygenase-1 and 2 (COX-1 and 2) enzymes, resulting in decreased formation of prostaglandin precursors. It has antipyretic, anti-inflammatory and analgesic properties.

• Pharmacokinetics

1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1364710/
2. https://reference.medscape.com/drug/colestid-Flurbiprofen -342452
3. https://go.drugbank.com/drugs/DB00375
4. https://www.sciencedirect.com/topics/medicine-and-dentistry/Flurbiprofen
5. https://europepmc.org/article/med/6988203