Flurbiprofen

Oral
Pain and inflammation associated with musculoskeletal and joint disorders
Adult: 150-200 mg daily in 2, 3 or 4 divided doses, may increase up to 300 mg daily in divided doses depending on severity of symptoms.
Renal impairment: Severe: Contraindicated.
Hepatic impairment: Severe: Contraindicated.

Oral
Osteoarthritis
Adult: 150-200 mg daily in 2, 3 or 4 divided doses, may increase up to 300 mg daily in divided doses depending on severity of symptoms.
Renal impairment: Severe: Contraindicated.
Hepatic impairment: Severe: Contraindicated.

Oral
Rheumatoid arthritis
Adult: 150-200 mg daily in 2, 3 or 4 divided doses, may increase up to 300 mg daily in divided doses depending on severity of symptoms.
Renal impairment: Severe: Contraindicated.
Hepatic impairment: Severe: Contraindicated.

Oral
Strains
Adult: 150-200 mg daily in 2, 3 or 4 divided doses, may increase up to 300 mg daily in divided doses depending on severity of symptoms.
Renal impairment: Severe: Contraindicated.
Hepatic impairment: Severe: Contraindicated.

Oral
Sprains
Adult: 150-200 mg daily in 2, 3 or 4 divided doses, may increase up to 300 mg daily in divided doses depending on severity of symptoms.
Renal impairment: Severe: Contraindicated.
Hepatic impairment: Severe: Contraindicated.

Oral
Ankylosing spondylitis
Adult: 150-200 mg daily in 2, 3 or 4 divided doses, may increase up to 300 mg daily in divided doses depending on severity of symptoms.
Renal impairment: Severe: Contraindicated.
Hepatic impairment: Severe: Contraindicated.

Oral
Dysmenorrhoea
Adult: Initially, 100 mg followed by 50 or 100 mg every 4-6 hours. Max: 300 mg daily.
Renal impairment: Severe: Contraindicated.
Hepatic impairment: Severe: Contraindicated.

Oral
Sore throat
Adult: As 8.75 mg lozenge: Dissolve 1 lozenge slowly in the mouth every 3-6 hours, as necessary. Max: 5 lozenges in 24 hours. Max duration: 3 days.
Renal impairment: Severe: Contraindicated.
Hepatic impairment: Severe: Contraindicated.

Ophthalmic
Prophylaxis of miosis during ocular surgery
Adult: As 0.03% solution: Instill 1 drop into the eye every 30 minutes starting 2 hours before surgery until 30 minutes prior to surgery.

Ophthalmic
Postoperative ocular inflammation
Adult: As 0.03% solution: Instill 1 drop into the eye (starting at 24 hours after surgery) 4 times daily for 1-3 weeks.

Mouth/Throat
Sore throat
Adult: As 8.75 mg spray: 3 actuations (1 dose) to the back of the throat every 3-6 hours, as necessary. Max: 5 doses in 24 hours. Max duration: 3 days.
Renal impairment: Severe: Contraindicated.
Hepatic impairment: Severe: Contraindicated.

Special Populations: Pharmacogenomics: Genetic polymorphism of CYP2C9 may affect the pharmacokinetics of flurbiprofen. The CYP2C9 genotype has multiple alleles identified as CYP2C9*1, CYP2C9*2 and CYP2C9*3, in which the CYP2C9*2 and *3 alleles are commonly associated with reduction of CYP2C9 activity. The frequencies of the two common variants vary among populations with distinct ethnic backgrounds. The prevalence of CYP2C9*2 and *3 is ¹/₃ in white populations. CYP2C9*2 allele does not exist in East Asian populations (Korean, Chinese, Japanese) while CYP2C9*3 allele exists in 4.6% Koreans, 3.5% Chinese and 2.8% Japanese. According to studies, individuals who are carriers of CYP2C9*1/*3 may have increased serum concentration and decreased clearance of flurbiprofen as compared to those with CYP2C9*1/*1 genotype. However, no significant changes in the same parameters were noted in individuals with CYP2C9*1/*2, except for the elimination half-life of the parent drug. The CYP2C9*3 allele substitution is found in the substrate recognition site (SRS) 5 which affects both substrate binding and catalytic activity while CYP2C9*2 substitution is not located in SRS. Studies suggest that individuals with known or suspected CYP2C9*1/*3 genotype may be advised to lower flurbiprofen doses than the usual dose to avoid abnormally high plasma levels due to reduced metabolic clearance.

Should be taken with food.

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).

Patients with history of mild to moderate heart failure, peripheral arterial disease, other risk factors for CV disease (e.g. hypertension, hyperlipidaemia, diabetes mellitus, smoking); SLE, asthma, oedema, hypovolaemia. Dehydrated and debilitated patients. Renal and hepatic impairment. Elderly. Pregnancy (1st-2nd trimester) and lactation. Patients with CYP2C9*1/*3 allele. Concomitant use of corticosteroids, SSRIs, antiplatelets, or anticoagulants. Not for prolonged use. Patient Counselling This drug may cause dizziness, drowsiness, fatigue and visual disturbances, if affected, do not drive or operate machinery. Monitoring Parameters Monitor blood pressure, CBC, chemistry profile, occult blood loss, periodic LFT, renal function (e.g. urine output, serum BUN, creatinine); ophthalmic exam (prolonged use), signs and symptoms of gastrointestinal bleeding.

Significant: Renal papillary necrosis (prolonged use). Rarely, anaphylactoid reactions, blood dyscrasias (e.g. agranulocytosis, thrombocytopenia, aplastic anaemia), hyperkalaemia. Cardiac disorders: Cardiac failure. Ear and labyrinth disorders: Tinnitus. Eye disorders: Eye irritation, eye pain, eye haemorrhage, prolonged mydriasis, eye hyperaemia, visual disturbance, miosis. Gastrointestinal disorders: Nausea, vomiting, diarrhoea, dyspepsia, flatulence, constipation, abdominal pain, melaena, haematemesis, ulcerative stomatitis, gastritis. Lozenge/throat spray: Throat irritation, mouth ulceration, oral pain or discomfort, oral paraesthesia, oropharyngeal pain. General disorders and administration site conditions: Fatigue, malaise. Hepatobiliary disorders: Rarely, jaundice. Investigations: Increased liver enzymes, prolonged bleeding time. Metabolism and nutrition disorders: Fluid retention. Nervous system disorders: Headache, dizziness, paraesthesia, tremor. Psychiatric disorders: Anxiety, insomnia, amnesia, depression, nervousness, somnolence. Respiratory, thoracic and mediastinal disorders: Rhinitis. Skin and subcutaneous tissue disorders: Rash, photosensitivity. Vascular disorders: Hypertension.
Potentially Fatal: Gastrointestinal inflammation, bleeding, ulceration or perforation, CV thrombotic events (e.g. myocardial infarction, stroke), bronchospasm. Rarely, hepatotoxicity (e.g. fulminant hepatitis, hepatic necrosis, hepatic failure), exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis.

Symptoms: Nausea, vomiting, headache, epigastric pain, gastrointestinal bleeding. Rarely, diarrhoea, disorientation, excitation, coma, drowsiness, dizziness, tinnitus, fainting, convulsions, acute renal failure and liver damage. Management: Symptomatic and supportive treatment. Consider administration of activated charcoal or perform gastric lavage within 1 hour of ingestion of a potentially toxic amount. Frequent or prolonged convulsions should be treated with intravenous diazepam or lorazepam. Monitor renal and liver function.

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.

Decreased rate of absorption with food.

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

Mouth/Throat: Store below 30°C. Protect from light. Ophthalmic: Store between 15-25°C. Oral: Store below 30°C. Protect from light.

Mouth/Throat Preparations / Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) / Other Eye Preparations

R02AX01 - flurbiprofen ; Belongs to the class of other throat preparations.
M02AA19 - flurbiprofen ; Belongs to the class of non-steroidal antiinflammatory preparations for topical use. Used in the treatment of joint and muscular pains.
M01AE09 - flurbiprofen ; Belongs to the class of propionic acid derivatives of non-steroidal antiinflammatory and antirheumatic products.
S01BC04 - flurbiprofen ; Belongs to the class of non-steroidal antiinflammatory agents. Used in the treatment of inflammation of the eye.