Indomethacin is a non-selective cyclooxygenase (COX) inhibitor, belonging to the non-steroidal anti-inflammatory drug (NSAID) class. It inhibits both COX-1 (constitutive enzyme involved in gastric mucosal protection and platelet function) and COX-2 (inducible enzyme mediating inflammation, pain, and fever). By blocking prostaglandin synthesis, indomethacin exerts:

• Anti-inflammatory effects: Reduced prostaglandins at sites of inflammation.
• Analgesic effects: Decreased pain signal sensitization.
• Antipyretic effects: Action on the hypothalamic thermoregulatory center.

Indomethacin is indicated for:

1. Inflammatory Joint Diseases:
   • Rheumatoid arthritis, osteoarthritis, ankylosing spondylitis.
2. Acute Gouty Arthritis: Rapid relief of pain and inflammation.
3. Musculoskeletal Disorders: Bursitis, tendonitis.
4. Patent Ductus Arteriosus (PDA): Intravenous use in neonates to promote ductus closure.
5. Off-Label Uses: Dysmenorrhea, pericarditis.

Adults:

• Oral: Initial dose 50–75 mg daily in divided doses; maintenance 25–50 mg 2–3 times daily (max 200 mg/day).
• Suppository: 100 mg once or twice daily (if oral route not feasible).

Neonates (PDA):

• IV: 0.1–0.3 mg/kg every 12–24 hours for 1–3 doses (BNF guidelines).

Special Populations:

• Elderly: Use lowest effective dose (increased GI/renal risk).
• Renal/Hepatic Impairment: Avoid in severe cases.

• Common: Nausea, dyspepsia, dizziness, headache.
• Serious:
  • Gastrointestinal: Ulcers, bleeding, perforation.
  • Cardiovascular: Hypertension, fluid retention, heart failure exacerbation.
  • Renal: Acute kidney injury, interstitial nephritis (due to reduced renal prostaglandins).
  • Hematologic: Prolonged bleeding time, thrombocytopenia.
  • CNS: Confusion, seizures (rare).

1. Contraindications:
   • Active peptic ulcer disease, severe heart failure, third-trimester pregnancy, hypersensitivity to NSAIDs.
2. Cautions:
   • History of GI bleeding, asthma, hypertension, coagulation disorders.
   • Avoid concurrent use with other NSAIDs or corticosteroids.
3. Monitoring:
   • Renal function, blood pressure, and CBC during prolonged therapy.

Indomethacin interacts with:

• Anticoagulants (e.g., warfarin): Increased bleeding risk.
• Antihypertensives (e.g., ACE inhibitors): Reduced efficacy.
• Diuretics (e.g., furosemide): Reduced diuretic effect; risk of renal impairment.
• Methotrexate: Increased methotrexate toxicity.
• Ciclosporin: Enhanced nephrotoxicity.
• SSRIs/SNRIs: Increased GI bleeding risk.

• Generic: Indomethacin.
• Brand Names: Indocin (US), Indocid (UK), Tivorbex (extended-release capsules).