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Indometacin – Uses, Mechanism & Side Effects

Indometacin is a potent anti-inflammatory drug belonging to the group of nonsteroidal anti-inflammatory drugs (NSAIDs), used to treat pain, fever, and inflammation.

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Things worth knowing about "Indometacin"

Indometacin is a potent anti-inflammatory drug belonging to the group of nonsteroidal anti-inflammatory drugs (NSAIDs), used to treat pain, fever, and inflammation.

What is Indometacin?

Indometacin (also known as Indomethacin) is a nonsteroidal anti-inflammatory drug (NSAID) with strong anti-inflammatory, analgesic, and antipyretic properties. It is one of the oldest and most potent drugs in its class and has been used in medicine since the 1960s. Indometacin is available by prescription in various forms, including tablets, capsules, suppositories, and topical gel.

Mechanism of Action

Indometacin works by inhibiting the enzyme cyclooxygenase (COX), specifically both the COX-1 and COX-2 isoforms. These enzymes are responsible for the production of prostaglandins – signaling molecules that trigger and sustain inflammatory responses, pain perception, and fever. By blocking COX enzymes, indometacin reduces prostaglandin synthesis, thereby decreasing inflammation, pain, and fever. Because it inhibits both COX isoforms, indometacin has a broader spectrum of action than selective COX-2 inhibitors, but also carries a higher risk of gastrointestinal side effects.

Indications

Indometacin is used in the treatment of various inflammatory and painful conditions:

Rheumatoid arthritis and other inflammatory joint diseases
Acute gout – indometacin is considered a first-line treatment for acute gout attacks
Ankylosing spondylitis (Bechterew disease)
Osteoarthritis with an inflammatory component
Bursitis and tendinitis
Pericarditis
In neonatology: closure of a patent ductus arteriosus in newborns
Treatment of certain cluster headaches and indomethacin-responsive headache disorders

Dosage and Administration

The dosage of indometacin depends on the indication, severity of the condition, and individual tolerance. Typical adult doses range from 25 mg to 150 mg per day, divided into two to three administrations. It should always be taken with food or milk to reduce gastric irritation. The lowest effective dose should be used for the shortest possible duration.

Side Effects

Indometacin can cause a range of side effects, particularly with prolonged use or higher doses:

Gastrointestinal: stomach pain, nausea, vomiting, diarrhea, peptic ulcers – these are the most common
Central nervous system: headache, dizziness, fatigue, confusion (especially in elderly patients)
Renal: possible deterioration of kidney function, particularly in patients with pre-existing kidney disease
Cardiovascular: increased risk of hypertension and cardiovascular events with long-term use
Bleeding risk: inhibition of platelet function may prolong bleeding time
Allergic reactions: skin rash, rarely severe hypersensitivity reactions

Contraindications

Indometacin should not be used in patients with:

Known hypersensitivity to indometacin or other NSAIDs
Active gastrointestinal ulcers or bleeding
Severe renal, hepatic, or cardiac insufficiency
Pregnancy from the 6th month onwards (may cause premature closure of the ductus arteriosus)
Concomitant use of anticoagulants without medical supervision

Drug Interactions

Indometacin may interact with numerous other medications:

Anticoagulants (e.g., warfarin, phenprocoumon): increased risk of bleeding
Antihypertensives: reduced blood pressure-lowering effect
Lithium and methotrexate: indometacin may increase their blood plasma levels
Other NSAIDs or corticosteroids: increased risk of gastrointestinal side effects
Diuretics: possible reduction in diuretic efficacy

References

Brunton L.L. et al. – Goodman & Gilman's: The Pharmacological Basis of Therapeutics. 13th edition. McGraw-Hill Education, 2018.
European Medicines Agency (EMA) – Indometacin: Product and prescribing information. Available at: https://www.ema.europa.eu
Vane J.R. – Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nature New Biology, 1971; 231(25):232–235.

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