Class
- Non-steroidal anti-inflammatory (NSAID)
Indomethacin
Commonly Prescribed for
(FDA approved in bold)
- Rheumatoid arthritis
- Ankylosing spondylitis
- Osteoarthritis
- Acute painful shoulder (bursitis, tendinitis)
- Acute gouty arthritis
- Migraine, tension-type, and cluster headache
- Indomethacin-responsive headache disorders: Hemicrania continua (HC)
- Paroxysmal hemicrania, primary cough headache, primary exertional headache, preorgasmic headache, primary stabbing or “ice-pick” headache, hypnic headache
- Suppression of uterine activity to prevent premature labor
Indomethacin
How the Drug Works
- Like other NSAIDs, inhibits cyclo-oxygenase (predominantly cox-1) thus inhibiting synthesis of prostaglandins, a mediator of inflammation
- The reason indomethacin is more effective than other NSAIDs for many headache disorders is unclear, but could be due to its structural similarities to serotonin, central vasoconstrictive and analgesic properties, or lowering of intracranial pressure. It also inhibits the metabolism of an active progesterone metabolite
Indomethacin
How Long Until It Works
- Migraine: (acute) less than 2 hours
- Indomethacin-responsive headache disorders: (preventive) less than a week after starting a given daily dose
Indomethacin
If It Works
- Continue to use
Indomethacin
If It Doesn’t Work
- Migraine: change to a triptan, dihydroergotamine, antiemetic or another NSAID
- Indomethacin-responsive headache disorders: reconsider the diagnosis
Indomethacin
Best Augmenting Combos for Partial Response or Treatment-Resistance
- Migraine: combine with triptan or antiemetic
Indomethacin
Tests
- None required
Adverse Effects (AEs)
Indomethacin
How Drug Causes AEs
- Effects on prostaglandins likely cause most GI and renal AEs
Indomethacin
Notable AEs
- Dyspepsia, dizziness, nausea, diarrhea most common
- Inhibition of platelet aggregation is usually mild
- Elevation in hepatic transaminases (usually borderline)
Indomethacin
Life-Threatening or Dangerous AEs
- GI ulcers and bleeding, increasing with duration of therapy
- May worsen depression, psychiatric disturbances, and parkinsonism
- May increase risk of fluid retention and edema, cardiovascular events, including myocardial infarction and stroke
- Renal insufficiency, proteinuria, and hyperkalemia
- Aseptic meningitis (rare)
- Hypersensitivity reactions – most common in patients with asthma
Indomethacin
Weight Gain
- Unusual
Indomethacin
Sedation
- Not unusual
Indomethacin
What to Do About AEs
- For significant GI or intracranial bleeding, stop drug. Some AEs respond to lowering dose
