I-Cin

Approved indications:

• Rheumatoid Arthritis (adult and juvenile): For the relief of signs and symptoms.
• Osteoarthritis: Including degenerative joint disease.
• Ankylosing Spondylitis.
• Acute Gouty Arthritis: Short-term management of pain and inflammation.
• Acute Bursitis and Tendinitis (e.g., shoulder bursitis, bicipital tendinitis).
• Patent Ductus Arteriosus (PDA) Closure: Intravenous formulation in premature neonates.
• Acute Pain: Short-term treatment of moderate to severe musculoskeletal pain.

Important off-label / clinically accepted uses:

• Pericarditis and post-pericardiotomy syndrome.
• Prevention of heterotopic ossification after orthopedic surgery.
• Management of Bartter syndrome–associated polyhydramnios in pregnancy (specialist use).
• Headache syndromes such as paroxysmal hemicrania and hemicrania continua.

Adults:

• Rheumatoid arthritis, osteoarthritis, ankylosing spondylitis:
  Oral: 20–40 mg/day in divided doses, may be increased to 150–200 mg/day in divided doses; use lowest effective dose.
  Sustained-release: 75 mg once or twice daily.
• Acute gouty arthritis: 50 mg orally three times daily until attack subsides (usually 3–5 days).
• Bursitis/tendinitis: 75–150 mg/day in divided doses for 1–2 weeks.

Pediatric (≥2 years for juvenile rheumatoid arthritis):
1–3 mg/kg/day in divided doses, maximum 4 mg/kg/day or 200 mg/day.

Patent ductus arteriosus (PDA) – Neonates:
IV: 0.1–0.25 mg/kg every 12–24 hours for 1–3 doses, depending on gestational age and response.

Elderly:
Initiate at lower end of dosing range; increased risk of GI and renal adverse effects.

Renal/hepatic impairment:
Avoid in advanced renal impairment; use with caution and monitor in mild to moderate impairment. Avoid in severe hepatic impairment.

Administration routes:
Oral (immediate or sustained-release capsules, suspension), rectal suppositories, intravenous (for PDA closure).

Indomethacin is a potent nonsteroidal anti-inflammatory drug (NSAID) that nonselectively inhibits cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) enzymes, leading to decreased synthesis of prostaglandins from arachidonic acid. Prostaglandins mediate inflammation, pain, and fever and help maintain gastrointestinal mucosal integrity, renal blood flow, and platelet aggregation. By reducing prostaglandin levels, indomethacin exerts anti-inflammatory, analgesic, and antipyretic effects, as well as promoting PDA closure via reduction of vasodilatory prostaglandins in the ductus arteriosus.

• Absorption: Rapid and complete oral absorption; peak plasma concentration in 0.5–2 hours.
• Bioavailability: ~100%.
• Distribution: Widely distributed; ~99% plasma protein bound. Crosses placenta and enters breast milk.
• Metabolism: Extensively hepatic via demethylation, deacylation, and glucuronidation (mainly CYP2C9 mediated).
• Half-life: ~4.5 hours (range 2.6–11 hours).
• Excretion: ~60% in urine (as metabolites and conjugates), ~33% in feces via biliary elimination.
• Onset: Analgesic effects within 30–60 minutes orally; anti-inflammatory effect within days.

• FDA Pregnancy Category: C (oral); D when used in the third trimester due to risk of premature ductus arteriosus closure and oligohydramnios.
• Lactation: Excreted in breast milk in small amounts. Potential for adverse effects (e.g., GI irritation, renal impairment) in the infant; avoid prolonged use during breastfeeding.
• Avoid during late pregnancy unless benefits outweigh risks.

• Primary class: Nonsteroidal Anti-inflammatory Drug (NSAID)
• Subclass: Acetic acid derivative

• Known hypersensitivity to indomethacin or other NSAIDs.
• History of asthma, urticaria, or allergic-type reactions after aspirin or NSAID use.
• Active GI bleeding or peptic ulcer disease.
• Severe heart failure.
• Recent or history of gastrointestinal perforation.
• Use in neonates with active bleeding, thrombocytopenia, renal impairment, untreated infection (PDA indication).

• Cardiovascular: Increased risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke.
• Gastrointestinal: Risk of bleeding, ulceration, and perforation, which may be fatal; risk higher in elderly.
• Renal: Risk of renal impairment; monitor renal function, especially in dehydration, heart failure, liver dysfunction.
• Hepatic: May cause hepatitis or elevated liver enzymes; discontinue if abnormal tests persist.
• CNS effects: Headache, dizziness, confusion, depression—caution in activities requiring alertness.
• Hematologic: May cause anemia and affect platelet function.
• Monitor BP, renal and liver function during long-term therapy.

Common:

• GI: Nausea, vomiting, dyspepsia, abdominal pain, diarrhea, constipation.
• CNS: Headache, dizziness, fatigue, depression.
• Renal: Fluid retention, mild renal function changes.

Serious:

• GI bleeding, ulceration, perforation.
• Myocardial infarction, stroke.
• Severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis).
• Hepatitis, jaundice.
• Renal failure.

Rare:

• Aseptic meningitis.
• Hematologic abnormalities (aplastic anemia, thrombocytopenia).

• Anticoagulants (e.g., warfarin): ↑ bleeding risk.
• Antiplatelets & SSRIs: ↑ GI bleeding risk.
• ACE inhibitors, ARBs, diuretics: ↓ antihypertensive effect; ↑ nephrotoxicity risk.
• Lithium: ↑ lithium levels/toxicity.
• Methotrexate: ↓ methotrexate clearance → ↑ toxicity.
• CYP2C9 inhibitors/inducers: Alter plasma concentrations.
• Alcohol: ↑ GI irritation and bleeding risk.
• Corticosteroids: ↑ risk of GI ulcer/bleeding.

• Regulatory agencies emphasize using lowest effective dose for shortest duration to minimize cardiovascular and gastrointestinal risks.
• Recent neonatal guidelines recommend strict monitoring for renal, GI, and hematologic adverse effects during PDA closure therapy.

• Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C–30°C.
• Protect from moisture and light.
• Suppositories: Store in a cool, dry place; may require refrigeration depending on formulation.
• IV preparation: Follow specific reconstitution and stability guidelines; protect from freezing.