A-Fenac K

A. Approved Indications

• Acute Pain: Relief of mild to moderate acute pain, including:
• Musculoskeletal pain (e.g., backache, sprains, strains)
• Dental pain
• Postoperative pain
• Primary Dysmenorrhea: Treatment of menstrual cramps.
• Migraine: Acute treatment of migraine attacks (with or without aura).
• Osteoarthritis (Flare-ups): Symptomatic relief during acute exacerbations.
• Rheumatoid Arthritis and Ankylosing Spondylitis: For rapid relief of inflammatory symptoms.

B. Clinically Accepted Off-label Uses

• Gout (acute attacks): As short-term anti-inflammatory therapy.
• Biliary and Renal Colic: For rapid onset analgesia.
• Post-traumatic Inflammation: Adjunct in localized trauma or post-injury pain.

Route of Administration: Oral (tablet, powder for oral solution)

Adults:

• Pain or Dysmenorrhea: 50 mg every 8 hours as needed. Max: 150 mg/day.
• Migraine: 50 mg at onset of symptoms. A second dose may be taken after 2 hours if needed (maximum 100 mg/day).
• Osteoarthritis / Rheumatoid Arthritis: 50 mg two or three times daily.
• Take with food or milk to reduce gastrointestinal discomfort.

Pediatrics:

• Not recommended for children under 14 years for routine use.
• Adolescents (14–18 years): Use with caution, based on weight and clinical indication under medical supervision.

Elderly:

• Use lowest effective dose due to increased risk of gastrointestinal, renal, and cardiovascular side effects.
• Start with 50 mg twice daily; titrate cautiously.

Renal Impairment:

• Use with caution in mild to moderate impairment.
• Avoid in severe renal impairment (eGFR <30 mL/min).

Hepatic Impairment:

• Caution required.
• Use lowest effective dose and monitor liver function regularly.

Diclofenac potassium is a non-selective nonsteroidal anti-inflammatory drug (NSAID) that primarily inhibits cyclooxygenase enzymes COX-1 and COX-2, which are responsible for the conversion of arachidonic acid to prostaglandins. By reducing prostaglandin synthesis, it alleviates inflammation, pain, and fever. The potassium salt form allows for rapid disintegration and absorption, leading to faster onset of analgesic action, making it particularly suitable for acute pain and migraine.

• Absorption: Rapid and complete from the gastrointestinal tract. Peak plasma concentrations reached within 30 to 60 minutes.
• Bioavailability: ~50–60% due to first-pass hepatic metabolism.
• Distribution: Widely distributed in body tissues. >99% protein-bound (mainly to albumin).
• Metabolism: Extensively metabolized in the liver via CYP2C9 and CYP3A4 into hydroxylated metabolites.
• Elimination: Excreted mostly in urine (60%) and feces (30%) as metabolites.
• Half-life: Terminal half-life ~1–2 hours.

• Pregnancy:
• FDA Category C (1st and 2nd trimester): Use only if clearly necessary.
• Category D (3rd trimester): Contraindicated due to risk of premature closure of ductus arteriosus and potential for fetal renal impairment.
• Lactation:
• Excreted in small amounts in breast milk.
• Use with caution; avoid prolonged use or high doses in breastfeeding mothers.
• Summary: Avoid during late pregnancy; use during lactation only under medical advice.

• Primary Class: Nonsteroidal Anti-inflammatory Drug (NSAID)
• Subclass: Non-selective COX inhibitor
• Salt Form: Potassium salt (fast-acting form of diclofenac)

• Hypersensitivity to diclofenac or other NSAIDs
• History of NSAID-induced asthma, urticaria, or allergic reactions
• Active gastrointestinal bleeding or peptic ulcer
• Severe hepatic or renal impairment
• Third-trimester pregnancy
• Known cardiovascular diseases (e.g., recent MI, heart failure) where NSAIDs are contraindicated
• Concurrent use with other NSAIDs or aspirin (increases risk of adverse effects)

• Gastrointestinal Risk: Increased risk of GI bleeding, ulceration, and perforation—especially in elderly or those with prior ulcer history.
• Cardiovascular Risk: May increase risk of thrombotic events (e.g., MI, stroke) with prolonged use or high doses.
• Renal Risk: NSAIDs may impair renal function; monitor serum creatinine in long-term use.
• Hepatic Risk: Elevated liver enzymes reported; monitor ALT/AST in chronic use.
• Dermatologic Reactions: Rare but serious skin reactions such as Stevens-Johnson Syndrome.
• Asthma: May trigger bronchospasm in aspirin-sensitive individuals.
• Sodium Retention: Can cause fluid retention and edema—caution in hypertension and CHF.

Common:

• Gastrointestinal: Nausea, abdominal pain, dyspepsia, diarrhea
• Central Nervous System: Headache, dizziness
• Dermatologic: Rash, itching

Less Common:

• Hepatic: Elevated liver enzymes
• Renal: Reduced creatinine clearance, renal insufficiency
• Cardiovascular: Edema, increased blood pressure

Serious (Rare):

• Gastrointestinal bleeding or perforation
• Myocardial infarction, stroke
• Anaphylaxis
• Stevens-Johnson Syndrome, Toxic Epidermal Necrolysis

• Anticoagulants (e.g., Warfarin): Increased risk of bleeding
• Antihypertensives (e.g., ACE inhibitors, ARBs, diuretics): Reduced efficacy; risk of renal impairment
• Other NSAIDs and corticosteroids: Increased risk of GI toxicity
• Methotrexate: May enhance toxicity due to decreased clearance
• Cyclosporine: Increased nephrotoxicity risk
• CYP2C9 Inhibitors (e.g., fluconazole): May increase diclofenac levels
• Alcohol: Increased GI bleeding risk
• Lithium: Diclofenac may raise serum lithium levels

• FDA and EMA: Reaffirmed cardiovascular warnings on all NSAIDs, including diclofenac potassium—particularly for long-term or high-dose use.
• WHO Pain Ladder: Includes NSAIDs like diclofenac as first-line for moderate pain.
• New Recommendations: Use the lowest effective dose for the shortest possible duration to minimize risks.
• EMA (2023): Advised caution with diclofenac in patients with pre-existing cardiovascular disease.

• Temperature: Store at 20°C to 25°C (68°F to 77°F)
• Humidity: Keep in a dry place
• Light: Store in original packaging to protect from light
• Handling:
• Keep out of reach of children
• Do not use if tablets are discolored or damaged
• Follow expiry date on the package
• Powder for Oral Solution: Use immediately after reconstitution if applicable