Indomethacin Side Effects: What to Expect and When to Call Your Doctor

Indomethacin is one of the most potent NSAIDs available — and with that potency comes a broader side effect profile than milder anti-inflammatory drugs. Knowing what to watch for can help you take indomethacin safely and catch serious problems early.

The Boxed Warnings: What You Must Know First

Like all NSAIDs, indomethacin carries FDA Boxed Warnings — the highest level of safety alert the FDA issues. There are two:

Cardiovascular thrombotic events: NSAIDs increase the risk of heart attack and stroke, which can be fatal. This risk is higher with longer use and higher doses, and in people with existing heart disease. This risk can appear even early in treatment.

GI bleeding, ulceration, and perforation: NSAIDs can cause serious GI events — including bleeding, ulcers, and perforations of the stomach or intestines — that can occur at any time and without warning symptoms. These events can be fatal.

Common Side Effects of Indomethacin

These side effects are relatively common and often improve as your body adjusts to the medication. Taking indomethacin with food or milk can reduce several of these:

Headache (paradoxically, indomethacin sometimes causes headaches even in doses used to treat them)

Dizziness or lightheadedness

Nausea and upset stomach (dyspepsia)

Heartburn and abdominal discomfort

Diarrhea or constipation

Drowsiness or fatigue — do not drive or operate heavy machinery if affected

Tinnitus (ringing in the ears) — discontinue and call your doctor if this occurs

CNS Side Effects: Why Indomethacin Is Different From Other NSAIDs

Indomethacin crosses the blood-brain barrier more readily than most other NSAIDs. This is responsible for some of its unique properties (like treating indomethacin-responsive headaches) but also for a higher rate of CNS side effects:

Headache (distinct from the pain being treated)

Drowsiness and cognitive impairment

Confusion and disorientation (especially in elderly patients)

Depression or mood changes

In rare cases: psychosis (particularly in elderly patients)

This is why the American Geriatrics Society (AGS) Beers Criteria identifies indomethacin as potentially inappropriate for older adults. Elderly patients are at significantly higher risk of CNS effects and GI toxicity.

Kidney Effects

Indomethacin reduces the production of prostaglandins that help maintain kidney blood flow. In patients with reduced kidney function, this can cause acute kidney injury. Signs to watch for include: decreased urination, swelling in hands, feet, or legs, unusual weight gain, increased blood pressure. Indomethacin should be used with caution — or avoided — in patients with pre-existing kidney disease, heart failure, or liver disease.

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Serious Side Effects: Call Your Doctor Immediately

Stop taking indomethacin and seek emergency care or call 911 if you experience:

Heart attack signs: Chest pain, pressure, or tightness; pain radiating to arm, neck, or jaw; shortness of breath

Stroke signs: Sudden confusion, weakness on one side of the body or face, slurred speech, sudden severe headache

GI bleeding: Black or tarry stools, bright red blood in stool, vomiting blood or material that looks like coffee grounds, severe stomach pain

Serious allergic reaction (anaphylaxis): Hives, difficulty breathing, swelling of the face, lips, tongue, or throat

Serious skin reactions: Rash, blistering, peeling skin — could be Stevens-Johnson Syndrome or TEN. Stop the medication immediately.

How to Reduce Side Effects

Take indomethacin with food, milk, or antacids to reduce GI irritation

Use the lowest effective dose for the shortest time necessary

Ask your doctor about a proton pump inhibitor (PPI) if you have GI risk factors

Avoid alcohol while taking indomethacin — it increases GI bleeding risk

Do not take other NSAIDs (ibuprofen, naproxen, aspirin) while on indomethacin without your doctor's guidance

For a detailed list of drug interactions to watch for, see our guide on Indomethacin drug interactions.