Flurbiprofen

Approved Indications:

• Osteoarthritis (mild to moderate): For symptomatic relief of joint pain, stiffness, and inflammation.
• Rheumatoid Arthritis (including juvenile RA): To reduce pain, swelling, and improve joint function.
• Ankylosing Spondylitis: To manage spinal inflammation and stiffness.
• Postoperative Pain: Short-term treatment of moderate to severe pain following surgical procedures.
• Dysmenorrhea: Relief from menstrual pain and cramps.
• Dental Pain: Used post-extraction or for procedures involving acute dental inflammation.
• Soft Tissue Injuries: Management of pain and inflammation from sprains, strains, or musculoskeletal trauma.
• Ophthalmic Uses (Flurbiprofen eye drops):
• Inhibition of intraoperative miosis during cataract surgery
• Postoperative inflammation control following ocular surgery

Clinically Accepted Off-Label Uses:

• Migraine-associated pain
• Chronic low back pain
• Temporomandibular joint (TMJ) disorders
• Topical application for localized musculoskeletal inflammation (Flurbiprofen gel/patch)

Oral Administration (Tablets):

• Adults:
• Osteoarthritis/Rheumatoid Arthritis: 200–300 mg/day in divided doses (100 mg BID to TID).
• Mild to Moderate Pain: 50–100 mg every 4–6 hours; maximum 300 mg/day.
• Dysmenorrhea: Initial 100 mg, then 50–100 mg every 6 hours as needed.
• Elderly:
• Start at the lower end of the dosage range.
• Monitor for gastrointestinal and renal adverse events.
• Pediatrics:
• Not routinely recommended orally for patients <18 years for systemic use, except under specialist advice (e.g., juvenile arthritis).

Topical Administration:

• Apply Flurbiprofen gel or patch 2–4 times daily over the affected area.
• Avoid broken skin, eyes, and mucous membranes.

Ophthalmic Solution (0.03%–0.1%):

• 1 drop into the operative eye every 30 minutes beginning 2 hours before surgery.
• Postoperative: 1 drop 4 times daily for up to 3 weeks as directed.

Special Populations:

• Renal Impairment: Use with caution; dose adjustment may be necessary. Monitor renal function.
• Hepatic Impairment: Use the lowest effective dose; close monitoring recommended.
• Avoid prolonged use in any population without reevaluation.

Flurbiprofen is a non-selective nonsteroidal anti-inflammatory drug (NSAID) that inhibits both cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) enzymes. By blocking these enzymes, flurbiprofen reduces the synthesis of prostaglandins, which are mediators of inflammation, pain, and fever. This inhibition leads to analgesic, anti-inflammatory, and antipyretic effects. In ophthalmic use, flurbiprofen prevents intraoperative miosis by inhibiting prostaglandin-mediated pupillary constriction.

• Absorption: Rapidly absorbed orally; peak plasma levels reached in 1–2 hours.
• Bioavailability: Approximately 80–90% (oral route).
• Distribution: Widely distributed; 99% bound to plasma proteins.
• Metabolism: Extensively metabolized in the liver via CYP2C9.
• Elimination Half-life: Approximately 3–6 hours.
• Excretion: Mainly via kidneys (60–70% as metabolites), with some fecal elimination.

• Pregnancy:
• FDA Category C (1st & 2nd trimester); Category D (3rd trimester)
• Avoid during third trimester due to risk of premature closure of fetal ductus arteriosus and oligohydramnios.
• Lactation:
• Small amounts may be excreted into breast milk.
• Use with caution; consider risk-benefit if breastfeeding.
• Note: Limited data in pregnancy and lactation. Avoid chronic use.

• Primary Class: Nonsteroidal Anti-inflammatory Drug (NSAID)
• Subclasses:
• Propionic acid derivatives
• Non-selective COX inhibitor
• Ophthalmic NSAID (when used as eye drops)

• Known hypersensitivity to flurbiprofen or other NSAIDs
• History of aspirin- or NSAID-induced asthma, urticaria, or anaphylaxis
• Active gastrointestinal bleeding or peptic ulcer
• Severe hepatic or renal impairment
• Advanced heart failure (NYHA Class III–IV)
• Perioperative pain management in coronary artery bypass graft (CABG) surgery
• Late pregnancy (third trimester)

• Cardiovascular: Increased risk of serious CV thrombotic events, MI, and stroke. Monitor in patients with existing CV risk factors.
• Gastrointestinal: May cause GI bleeding, ulceration, and perforation. Use with PPI in high-risk patients.
• Renal: Risk of nephrotoxicity, especially in dehydrated, elderly, or renally compromised patients.
• Hepatic: Monitor liver enzymes periodically.
• Ophthalmic: Risk of delayed wound healing or keratitis with prolonged use.
• Hypersensitivity: Risk of serious skin reactions (e.g., Stevens-Johnson syndrome).
• Monitoring: CBC, LFTs, renal function, and signs of GI bleeding in long-term therapy.

Common (≥1%):

• Gastrointestinal: Nausea, dyspepsia, abdominal pain, diarrhea, constipation
• Neurological: Headache, dizziness, drowsiness
• Dermatological: Rash, pruritus
• Ophthalmic (eye drops): Burning, stinging, blurred vision

Less Common/Rare:

• GI bleeding, ulceration, hematemesis
• Elevated liver enzymes
• Tinnitus
• Edema, hypertension
• Bronchospasm or asthma exacerbation
• Anemia or thrombocytopenia

Serious:

• Anaphylaxis
• Stevens-Johnson syndrome
• Acute renal failure
• Myocardial infarction or stroke (with long-term use)

• Increased bleeding risk: With anticoagulants (warfarin), antiplatelets (aspirin, clopidogrel), SSRIs
• Nephrotoxicity risk: With ACE inhibitors, ARBs, diuretics, cyclosporine
• Methotrexate & lithium: May increase toxicity of both; monitor levels
• CYP2C9 inhibitors (e.g., fluconazole): May increase flurbiprofen levels
• NSAIDs + Aspirin: May reduce cardioprotective effect of low-dose aspirin
• Alcohol: Increases risk of GI ulceration and bleeding

• EMA & FDA Warning Updates (Recent Years):
• Reinforced CV and GI risks with all non-selective NSAIDs
• Emphasis on lowest effective dose for shortest duration
• Ophthalmic Use: Approved updates on preventing miosis during eye surgery
• Topical NSAID formulations: Safer GI profile; increasingly recommended for localized inflammation

• Oral Tablets:
• Store below 25°C
• Protect from moisture and direct sunlight
• Keep in original container
• Topical Gel/Patch:
• Store below 30°C
• Do not freeze
• Keep away from open flames or heat
• Ophthalmic Solution:
• Store between 15°C to 25°C
• Protect from light
• Discard within 28 days after opening
• Do not use if solution changes color or becomes cloudy