Indomethacin

Indomethacin is an NSAID available in multiple forms, each approved for specific uses:

• Oral capsules (immediate-release), oral suspension (including Indocin oral suspension), and rectal suppositories (including Indocin suppositories): moderate to severe rheumatoid arthritis (including acute flares), moderate to severe ankylosing spondylitis, moderate to severe osteoarthritis, acute painful shoulder (bursitis and/or tendinitis), and acute gouty arthritis
• Extended-release oral capsules: all of the above arthritis and shoulder indications — but not acute gouty arthritis
• Indomethacin for Injection (intravenous): approved only for closing a hemodynamically significant patent ductus arteriosus (a blood vessel near the heart that fails to close after birth) in premature infants weighing 500–1,750 g, when standard medical management has not been effective

Indomethacin blocks two enzymes — COX-1 and COX-2 (cyclooxygenase) — that the body uses to produce prostaglandins. Prostaglandins are natural chemicals that sensitize pain receptors, trigger inflammation, and promote fever. By cutting prostaglandin production, indomethacin reduces pain, swelling, and inflammation throughout the body. In premature infants, the same prostaglandin-lowering action helps close the patent ductus arteriosus, a blood vessel that prostaglandins normally keep open.

The right form and schedule depend on what condition is being treated — always follow your prescriber's specific instructions and use the lowest effective dose for the shortest time needed.

• Oral capsules and oral suspension: typically taken multiple times daily, with doses spread throughout the day; take with food or antacids to protect the stomach
• Extended-release capsules: designed for once-daily dosing (or twice daily for higher-dose regimens); must be taken with food, immediately after a meal, or with antacids — never on an empty stomach; not appropriate for acute gout
• Rectal suppositories: can substitute for oral capsules for most indications; for rectal use only — not oral or intravaginal; note that blood levels may differ somewhat from the oral forms
• Intravenous injection: given only in a hospital by healthcare professionals, as a course of three doses at 12–24 hour intervals, for premature infants with patent ductus arteriosus

The most common side effects of indomethacin — reported in more than 3% of patients — include headache, dizziness, upset stomach (dyspepsia), and nausea. Other frequently reported effects include:

• Vomiting, diarrhea, abdominal pain, or constipation
• Bloating and gas (flatulence)
• Drowsiness, fatigue, or feeling "muzzy" or mentally foggy
• Vertigo, anxiety, or low mood
• Ringing in the ears (tinnitus)
• Fluid retention or mild swelling (edema)

Seek medical help right away for serious reactions: signs of GI bleeding (black or bloody stools, vomiting blood), chest pain or stroke symptoms, yellowing of the skin or eyes, severe skin reactions (blistering, peeling), significant decrease in urination, or any signs of a severe allergic reaction such as swelling of the face or difficulty breathing.

• Heart attack and stroke: Indomethacin — like all NSAIDs — raises the risk of serious and potentially fatal cardiovascular events. The risk can begin early in treatment and rises with longer use and higher doses. It is contraindicated right after coronary artery bypass graft (CABG) surgery and should be used with caution in people with existing heart disease.
• Stomach and intestinal bleeding: Serious GI bleeding, ulcers, and perforation can occur at any time without warning symptoms. Elderly patients and those with a prior history of ulcers or GI bleeding are at much higher risk.
• Kidney problems: Long-term use can damage the kidneys. People who are dehydrated, elderly, have kidney or liver disease, or take diuretics and ACE inhibitors are most vulnerable. Do not combine with triamterene.
• Liver injury: Rare but serious liver damage has been reported. Watch for nausea, fatigue, jaundice (yellowing of skin/eyes), or right-sided abdominal tenderness.
• Pregnancy risks: Avoid from about 20 weeks (risk of reduced amniotic fluid and fetal kidney harm) and completely avoid from about 30 weeks onward (risk of premature closure of a vital fetal blood vessel).
• Serious skin reactions: Rare but life-threatening skin conditions including Stevens-Johnson Syndrome and toxic epidermal necrolysis have been reported. Stop the drug at the first sign of rash or skin blistering.
• CNS effects: Indomethacin may cause drowsiness, dizziness, depression, or aggravate epilepsy and Parkinson's disease. Use caution when driving or operating machinery.
• Eye changes: Corneal deposits and retinal changes have been reported with long-term use. Report any vision changes to your prescriber.

Indomethacin has several important drug interactions that can raise the risk of serious side effects:

• Warfarin and other anticoagulants: combined use significantly increases bleeding risk
• Aspirin (analgesic doses): not generally recommended together — increases GI bleeding risk without added benefit; indomethacin is not a substitute for low-dose aspirin for heart protection
• SSRIs and SNRIs (e.g., fluoxetine, venlafaxine): raise bleeding risk when combined with indomethacin
• ACE inhibitors, ARBs, beta-blockers: indomethacin may blunt their blood pressure-lowering effect; in elderly or dehydrated patients, kidney function may worsen
• Diuretics (furosemide, thiazides): indomethacin may reduce their effectiveness; monitor blood pressure and kidney function
• Triamterene (potassium-sparing diuretic): this combination should be avoided — reported cases of reversible acute kidney failure
• Digoxin: indomethacin raises digoxin blood levels and prolongs its half-life — digoxin levels should be monitored
• Lithium: indomethacin raises lithium levels, increasing toxicity risk — monitor for lithium toxicity symptoms
• Methotrexate and cyclosporine: indomethacin may increase toxicity of both drugs; monitor closely
• Other NSAIDs or salicylates (especially diflunisal): greatly increases GI toxicity risk; avoid combining — diflunisal in particular can cause fatal GI hemorrhage
• Pemetrexed (a chemotherapy drug): indomethacin should be avoided around the time pemetrexed is given due to increased toxicity risk
• Probenecid: raises indomethacin blood levels; lower doses of indomethacin may be needed

This is not a complete list of interactions. Always talk with your doctor or pharmacist before starting, stopping, or changing any medication.

• Do not take if you have had a severe allergic reaction (anaphylaxis) or aspirin/NSAID-triggered asthma, hives, or breathing problems
• Do not take right before or after coronary artery bypass graft (CABG) heart surgery
• Do not take if you have a history of proctitis or recent rectal bleeding (for suppository forms)
• Tell your doctor if you have heart disease, a recent heart attack, high blood pressure, or heart failure
• Tell your doctor if you have kidney disease, liver disease, or are dehydrated
• Tell your doctor if you have a history of stomach ulcers or gastrointestinal bleeding
• Tell your doctor if you have epilepsy, Parkinson's disease, or depression — indomethacin may worsen these
• Pregnancy: limit use from about 20–30 weeks gestation; avoid entirely from about 30 weeks onward due to serious fetal risks
• Breastfeeding: indomethacin may appear in breast milk; discuss with your prescriber whether to continue
• Trying to conceive: NSAIDs including indomethacin may cause reversible delay in ovulation; consider stopping if you are having difficulty getting pregnant
• Children: safety and effectiveness in children 14 years and younger have not been established for extended-release capsules; use in younger children requires close medical supervision and liver monitoring
• Older adults: at higher risk for serious stomach bleeding and kidney problems; use with extra caution

Taking too much indomethacin typically causes drowsiness, nausea, vomiting, and stomach pain — symptoms that usually improve with supportive care. In more serious cases, high blood pressure, acute kidney failure, respiratory depression, or loss of consciousness can occur, though these are rare. If you suspect an overdose, call Poison Control at 1-800-222-1222 or seek emergency care immediately — there is no specific antidote, but treatment is supportive.

Indomethacin has pain-relieving (analgesic), anti-inflammatory, and fever-reducing (antipyretic) properties, all linked to its suppression of prostaglandin production. By reducing prostaglandins in peripheral tissues, it lowers the sensitivity of pain-sensing nerves and dampens the inflammatory response. In premature infants, this prostaglandin reduction promotes closure of the patent ductus arteriosus, a blood vessel that prostaglandins keep open after birth.

Oral indomethacin is rapidly and nearly completely absorbed — the immediate-release capsule and oral suspension reach peak blood levels in about 2 hours, with roughly 90% of the dose absorbed within 4 hours. Extended-release capsules are designed to release the drug more gradually over about 12 hours, producing steadier blood levels with less fluctuation. Indomethacin is about 99% bound to proteins in the bloodstream, crosses into the brain and the placenta, and appears in breast milk. It is broken down in the liver and eliminated mainly through the urine (about 60%) and feces (about 33%), with a half-life of approximately 4.5 hours.

Store at 20° to 25°C (68° to 77°F) . Protect from moisture