Indomethacin

Is indomethacin safe?

For a short course in a healthy adult, the risks are real but manageable. For long-term use, or for anyone over 65, there are usually better choices. Indomethacin has been sold in the US since 1965, and many doctors still reach for it in a gout flare. It works, but it has more side effects than the NSAIDs that came after it.

Two reviews set the picture. A 2011 review of population studies found indomethacin raised the risk of heart attack and stroke by 30% compared with no NSAID, and its authors wrote that this cast doubt on its continued use. A 2012 analysis put its stomach risk level with naproxen at about four times non-use. We score it 67, below naproxen (73) and diclofenac (69) but above piroxicam (65).

Indomethacin for gout

Gout is the main reason people are prescribed indomethacin today. The US label gives 50 mg three times a day until the pain is tolerable, then a quick cut to zero. Relief usually starts within 2 to 4 hours, tenderness and heat ease within 24 to 36 hours, and swelling goes down over 3 to 5 days.

The evidence does not single it out. A 2021 Cochrane review of 28 gout trials found:

• older NSAIDs and coxibs such as celecoxib gave the same relief, but older NSAIDs led to about twice as many side effects and more people stopping
• steroids (glucocorticoids) worked as well as NSAIDs, with fewer side effects overall
• comparisons of one NSAID with another were too weak to pick a winner

So indomethacin is one reasonable option for a short flare, not the only one. The 2020 American College of Rheumatology gout guideline strongly recommends colchicine, an NSAID or a steroid for flares, without ranking them. If you have heart, kidney or stomach problems, ask whether a steroid, colchicine or another NSAID would suit you better.

Heart and stomach

The 2011 review in PLOS Medicine pooled the large population studies on NSAIDs and heart attacks and strokes:

Directly against naproxen, indomethacin's risk was 23% higher, a difference the authors judged statistically significant. Few studies reported doses, so it is not clear how much the risk rises at higher doses.

On the stomach, the 2012 SOS meta-analysis put indomethacin at 4.14 times the risk of serious complications seen with no NSAID, close to naproxen (4.10), higher than meloxicam (3.47) and well below piroxicam (7.43). In studies that looked only at bleeding, it was 5.64 times.

Headaches, dizziness and the brain

This is what sets indomethacin apart from other NSAIDs. In the clinical trials on the US label, 11.7% of people had headaches, and 3% to 9% had dizziness. The label adds drowsiness, depression, confusion and, rarely, psychotic episodes. It says to use indomethacin with great care in people with depression or other psychiatric illness, epilepsy or Parkinson's disease, and to stop it if severe effects appear.

The 2023 Beers Criteria, the main US list of medicines older adults should avoid, put indomethacin on that list. They say it has the most side effects of all NSAIDs, including more effects on the brain. Long use has also caused deposits in the cornea and changes in the retina, so the label advises eye checks and stopping if blurred vision appears.

Who should be careful

Talk to your doctor before starting or continuing indomethacin if you:

• are over 65
• have heart disease, have had a stroke, or have high blood pressure or heart failure
• have had a stomach ulcer or bleed, or take a blood thinner, an SSRI, a steroid or low-dose aspirin
• have kidney disease, or take triamterene, another potassium-sparing diuretic, lithium, digoxin or methotrexate
• have depression, epilepsy or Parkinson's disease
• have had asthma, hives or swelling after aspirin or another NSAID, or are pregnant

Do not take it with other NSAIDs. In an overdose, call Poison Control on 1-800-222-1222 in the US or NHS 111 in the UK. A lower score is no reason to stop a medicine your doctor prescribed; ask at your next visit whether another option would suit you better.

How we scored it

Dependence (97), track record (92) and overdose marginOverdose marginHow far a normal dose is from a harmful one. A wide margin means an accidental extra dose is unlikely to cause serious harm.More in the glossary (82) are strong. Serious side effects (50) are low because indomethacin combines a heart risk above most NSAIDs, a stomach risk like naproxen's and frequent headaches and dizziness. Regulatory warnings (40) reflect the US boxed warningBoxed warningThe strongest safety warning the US FDA puts on a medicine's label, printed inside a black border at the top.More in the glossary, the extra label warnings on the brain and eyes, and the Beers advice to avoid it after 65.