A-Fenac

A. Approved Indications

• Rheumatoid Arthritis
• Osteoarthritis
• Ankylosing Spondylitis
• Acute Musculoskeletal Pain
• Acute Gout
• Primary Dysmenorrhea
• Postoperative Pain and Inflammation (dental, orthopedic, gynecological)
• Migraine (acute treatment, specific oral formulations only)
• Ophthalmic Inflammation (post-cataract surgery and allergic conjunctivitis, eye drop form)

B. Clinically Accepted Off-label Uses

• Bursitis and tendinitis
• Pain in cervical/lumbar spondylosis
• Renal colic (IM formulation)
• Soft tissue injuries (topical form)
• Post-traumatic inflammation

Route of Administration: Oral, Rectal, IM, IV, Topical, Ophthalmic

Oral:

• Adults:
• Osteoarthritis: 100–150 mg/day in 2–3 divided doses
• Rheumatoid arthritis: 150–200 mg/day in 2–3 divided doses
• Ankylosing spondylitis: 100–125 mg/day in 2–3 divided doses
• Dysmenorrhea: 50 mg TID at onset of symptoms
• Extended-release: 100 mg once daily

Injection (IM):

• 75 mg once or twice daily, maximum 150 mg/day, up to 2 days

Rectal:

• 50–100 mg once or twice daily depending on indication

Topical:

• Apply 2–4 g to affected area 3–4 times daily

Ophthalmic:

• 1 drop in the affected eye(s) up to 4 times daily depending on condition

Special Populations:

• Elderly: Start at lowest effective dose; monitor renal/hepatic function
• Renal Impairment: Avoid in severe impairment; dose adjustment in moderate cases
• Hepatic Impairment: Use with caution; monitor LFTs regularly
• Pediatrics: Not routinely recommended unless specifically prescribed

Diclofenac sodium is a non-selective NSAID that exerts its action by inhibiting both cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) enzymes, leading to a decreased synthesis of prostaglandins. Prostaglandins are responsible for pain, inflammation, and fever. Diclofenac also inhibits leukocyte migration and reduces vascular permeability at inflammation sites. This dual action contributes to both its anti-inflammatory and analgesic effects across a range of tissues.

• Absorption: Rapid and nearly complete following oral administration; peak levels within 1–2 hours
• Bioavailability: ~50–60% due to first-pass hepatic metabolism
• Distribution: Widely distributed; >99% bound to plasma proteins
• Metabolism: Hepatic via CYP2C9 and CYP3A4; forms hydroxylated and conjugated metabolites
• Elimination: Primarily via urine (60%) and bile (35%) as metabolites
• Half-life: 1–2 hours (oral); ~3 hours (extended-release formulations)

• Pregnancy:
• FDA Pregnancy Category: C (1st and 2nd trimester), D (3rd trimester)
• Avoid in the third trimester due to risk of fetal cardiovascular complications (e.g., premature closure of the ductus arteriosus)
• Lactation:
• Present in breast milk in small amounts; short-term use generally considered safe
• Use with caution; avoid long-term use in breastfeeding women

• Primary Class: Nonsteroidal Anti-inflammatory Drug (NSAID)
• Subclass: Non-selective COX inhibitor, Acetic acid derivative

• Known hypersensitivity to diclofenac or other NSAIDs
• History of NSAID-induced asthma, urticaria, or allergic-type reactions
• Active gastrointestinal ulceration or bleeding
• Severe hepatic or renal impairment
• Severe heart failure or recent cardiovascular surgery (e.g., CABG)
• Third trimester of pregnancy
• Rectal formulation contraindicated in proctitis or recent rectal bleeding

• Gastrointestinal Risk: May cause serious GI bleeding, ulceration, or perforation
• Cardiovascular Risk: Increased risk of myocardial infarction, stroke, and thrombotic events with long-term/high-dose use
• Hepatic Monitoring: Risk of elevated liver enzymes; monitor LFTs periodically
• Renal Monitoring: NSAIDs may reduce renal perfusion and worsen kidney function
• Hematologic: May prolong bleeding time; caution in patients on anticoagulants
• Photosensitivity: Rare skin reactions; advise sun protection for topical use

Common:

• GI: Nausea, dyspepsia, abdominal pain, diarrhea
• CNS: Headache, dizziness
• Dermatologic: Rash (topical), application-site irritation (topical)

Less Common:

• Edema, hypertension
• Elevated liver enzymes
• Visual disturbances (eye drops)

Serious/Rare:

• GI ulceration or bleeding
• Hepatotoxicity, hepatitis
• Nephrotoxicity
• Stevens-Johnson syndrome
• Anaphylaxis

• Anticoagulants (e.g., warfarin): Increased risk of bleeding
• Antihypertensives (ACE inhibitors, ARBs, diuretics): Reduced efficacy; risk of renal impairment
• Other NSAIDs or corticosteroids: Increased GI toxicity
• Methotrexate: Enhanced toxicity due to reduced clearance
• Lithium: Increased serum levels and toxicity risk
• CYP2C9 inhibitors (e.g., fluconazole): May elevate diclofenac levels
• Alcohol: Increases GI bleeding risk

• FDA and EMA reinforce boxed warnings about cardiovascular and GI risks with NSAID use.
• NICE and other international guidelines recommend using the lowest effective dose for the shortest possible duration.
• Topical forms are increasingly recommended for localized pain to reduce systemic risks.

• Oral/Injectable Forms:
• Store at 20°C to 25°C (68°F to 77°F)
• Protect from moisture and light
• Topical Gel/Patch:
• Store below 25°C (77°F); do not freeze
• Close cap tightly after use
• Ophthalmic Drops:
• Store at 2°C to 25°C (36°F to 77°F)
• Discard 28 days after opening bottle (unless otherwise labeled)