Indomethacin is one of the oldest NSAIDs available. It can help bring a normal life back to those that have debilitating joint pain and headaches. However, it causes more side effects than other similar drugs. Read on to learn more about its uses, possible side effects, and drug interactions to look out for.
What is Indomethacin?
Indomethacin is a prescription medication that belongs to a group of drugs called NSAIDs, which also includes aspirin, Advil, Aleve, and several other medications.
Like other NSAIDs, indomethacin is primarily used to relieve pain and reduce inflammation.
Brand names for indomethacin include Indocin, Indocid, and Tivorbex. Outside of the US, the generic name is indometacin.
Indomethacin is FDA-approved for the treatment of several joint diseases including rheumatoid arthritis, osteoarthritis, gout, as well as inflammation of the spine and tendons.
Off-label uses in the U.S. include treating headaches, chronic back pain, menstrual cramps, and delaying premature births.
Mechanism of Action
Indomethacin belongs to a class of medications called NSAIDs (which stands for nonsteroidal anti-inflammatory drugs).
NSAIDs (including indomethacin) primarily work by blocking enzymes called COX-1 and COX-2. These two enzymes are responsible for creating prostaglandins in the body. Prostaglandins are hormone-like compounds that play a role in inflammation, blood flow, stomach acidity, pain sensitivity, and more .
By blocking COX enzymes, indomethacin reduces the production of prostaglandins, which ultimately reduces pain and inflammation .
Prostaglandins can also disrupt the development of blood vessels in premature babies as well as induce labor in pregnant women. Indomethacin can prevent these effects by blocking prostaglandin production [1, 2].
There is also evidence that indomethacin may be particularly effective for certain types of migraines due to its unique ability to constrict blood vessels in the brain .
Uses of Indomethacin
1) Rheumatoid Arthritis
Rheumatoid arthritis is an autoimmune disorder that causes the immune system to mistakenly attack its own joints. This results in pain, inflammation, and stiffness. Treatment can be complex, involving multiple medications, physical therapy, or possibly surgery.
Indomethacin is sometimes used to help relieve the symptoms of rheumatoid arthritis. A number of clinical trials show that indomethacin can reduce pain and stiffness while improving grip strength [3, 4, 5, 6, 7].
However, in many of these studies, indomethacin was associated with significantly more side effects compared to other NSAIDs [3, 4, 5, 6, 7].
Osteoarthritis develops as the protective cartilage of the joints gradually breaks down over time, which causes joint pain and stiffness. Indomethacin is FDA-approved to treat this condition.
A 12-week randomized trial of 140 patients with osteoarthritis of the knee suggests that indomethacin is as effective as piroxicam (another NSAID) for reducing symptoms. However, twice as many patients on indomethacin dropped out of the study due to side effects compared to patients taking piroxicam .
Another randomized trial of 64 patients with osteoarthritis of the knee found that etodolac (another NSAID) may be more effective at improving symptoms, such as pain, tenderness, and mobility compared to indomethacin. Once again, significantly more people on indomethacin reported side effects .
Gout is a form of arthritis that can lead to recurring attacks of sharp pain, swelling, and redness, which usually affect the feet. Inflammation is caused by tiny crystals that form on the joints and tendons when uric acid levels in the blood are too high. Persistently high uric acid levels can deform the joints, damage the kidneys, and cause kidney stones .
NSAIDs have long been one of the preferred treatments for gout due to their effectiveness and low cost. Research shows that NSAIDs, including indomethacin, can improve gout symptoms, such as pain, tenderness, heat, and swelling [11, 10].
However, there is evidence that certain NSAIDs may be better tolerated than others. For example, a randomized trial of 142 gout patients found that etoricoxib (a selective NSAID) was associated with about 24% fewer side effects than indomethacin .
4) Inflammation of the Spine (Ankylosing Spondylitis)
Ankylosing spondylitis is a form of chronic arthritis that causes long-term autoimmune inflammation of the joints inside the spine and pelvis. This can lead to back pain and stiffness that becomes worse over time.
This joint disease has no cure, but different strategies like surgery, physical therapy, and medication can relieve the pain and delay disease progression .
NSAIDs are typically the first-line treatment for this condition. Researchers recently conducted a systematic review of 39 clinical trials including 4,356 patients to evaluate the safety and effectiveness of different NSAIDs for ankylosing spondylitis. In regards to indomethacin, researchers found the following :
- Indomethacin provides much greater pain relief than placebo
- Indomethacin is as effective as other NSAIDs
- More people experience side effects on indomethacin than on other NSAIDs
5) Bursitis and Tendinitis of the Shoulder
Bursitis refers to inflammation of the fluid-filled sacs that cushion muscles, tendons, and bones. Tendinitis, sometimes called tennis elbow, is an inflammation of the tendons usually caused by injury or repetitive movements.
Indomethacin is FDA-approved to treat both these conditions when they affect the shoulder.
Several clinical trials show that indomethacin is effective for providing short-term pain relief in bursitis and tendinitis. However, in most of these studies, indomethacin is linked to higher numbers of side effects [15, 16, 17, 18, 19].
6) Heart Defects in Infants (Patent Ductus Arteriosus)
Patent Ductus Arteriosus (PDA) is a heart condition that commonly affects premature infants. It occurs when a blood vessel in the heart does not close off properly, which allows blood to leak into unwanted areas like the lungs and cause blood flow disturbances .
This condition can be treated surgically or by using NSAID medications. Prostaglandins are responsible for keeping this blood vessel open. By blocking prostaglandin production, NSAIDs can potentially help seal off the open vessel .
Commonly used NSAIDs for PDA include indomethacin and ibuprofen. According to some estimates, NSAIDs can successfully treat this defect in about 67% of infants .
A systematic review of 68 clinical trials including 4,802 infants shows that high dose ibuprofen may be more effective and safer than indomethacin. The researchers found that indomethacin was more likely to cause gut injury in infants .
Indomethacin is sometimes used for several off-label conditions, which we’ll discuss in the following sections. If you are prescribed indomethacin, always take the medication as directed by your doctor.
7) Migraines and Headaches
NSAIDs are frequently used to relieve headaches and migraines. Headaches can be classified based on the severity of the pain, the location of the pain, additional symptoms, and other factors.
Some headaches belong to a group called “indomethacin-responsive headaches”. This unique set of headaches responds very well to indomethacin, while other NSAIDs have little to no effect.
Indomethacin-responsive headaches include [22, 23]:
- Cough headaches
- Exercise headaches
- Cluster headaches, which are rare and severely painful
- Headaches from sexual activity
- Stabbing headaches
- Coin-shaped (nummular) headaches
- Hypnic headaches, which wake people from sleep
- Several rare types of headache disorders
A systematic review of 81 clinical trials found that indomethacin is very effective for the types of headaches mentioned above, although a small number of people don’t respond to treatment .
Interestingly, indomethacin can actually trigger or worsen headaches in some people, according to the same review. This unwanted effect becomes more likely with higher drug doses .
Combination drugs like Difmetrè (indomethacin, prochlorperazine, and caffeine) are also used to provide migraine relief. In a randomized trial of 112 patients, this combination provided more relief from migraine attacks than the anti-migraine drug sumatriptan .
NSAIDs are sometimes used to prevent migraines as well. However, a systematic review of 49 clinical trials concluded that there is not enough evidence to determine the effectiveness of indomethacin for preventing migraines .
8) Chronic Back Pain
About 80% of adults experience lower back pain at some point in their lives. Back pain that lasts for 12 weeks or longer becomes a chronic condition. NSAIDs are commonly used for back pain, especially to help with short-term flare-ups .
NSAIDs (including indomethacin) are slightly more effective than placebo at reducing back pain and improving disability, according to a systematic review of 13 clinical trials including 1,354 people. The review also found no major differences in effectiveness between NSAIDs .
9) Menstrual Cramps
NSAIDs are usually one of the first medications used for painful periods.
A meta-analysis of 72 clinical trials including 5,723 patients evaluated the effectiveness of 13 drugs for menstrual cramps. Researchers found that indomethacin was better than aspirin for pain relief but caused more side effects. Other common NSAIDs, like naproxen and ibuprofen, appeared to be more effective than indomethacin .
Heavy bleeding and pain are the most common reasons women stop using IUDs (intrauterine devices) as birth control. A review of 15 clinical trials totaling 2,702 patients suggests that NSAIDs (including indomethacin) are effective at reducing both heavy bleeding and pain caused by IUDs .
10) Delaying Labor and Birth
Premature birth is when a woman gives birth before reaching 37 weeks of pregnancy and is one of the leading causes of death in infants .
Several different types of drugs can be used to delay labor and birth. The choice of medication depends on factors like how far along the pregnancy is, the mother’s medical history, and side effects.
Indomethacin is sometimes used to reduce contractions, which can delay birth for at least 48 hours .
However, a systematic review of 20 clinical trials including 1,509 women concluded that indomethacin doesn’t offer any clear benefit to the baby or the mother, compared to placebo or other medications. Indomethacin was able to delay birth, but it didn’t decrease the risk of infant death .
How Does Indomethacin Compare to Other NSAIDs?
Indomethacin is a non-selective NSAID, meaning it affects both COX-1 and COX-2 enzymes. In comparison, selective NSAIDs (like Celebrex or Mobic) only block COX-2, which means selective NSAIDs typically cause less side effects.
However, even among non-selective NSAIDs, indomethacin tends to be associated with more side effects.
A number of systematic reviews looking at indomethacin for arthritis-related conditions, menstrual cramps, and heart defects in newborns have all found that this drug causes significantly more side effects compared to other NSAIDs [14, 9, 8, 28, 21].
On the other hand, indomethacin has the unique ability to provide pain relief in several rare forms of headaches and migraines where other NSAIDs are ineffective .
Below are some reported side effects of indomethacin. If any side effects persist or worsen, let your doctor know. This is also not a complete list of possible side effects. Tell your doctor if you experience any serious side effects or notice any effects not listed here.
About 30 to 60% of people who take indomethacin experience side effects. Most side effects are dose-dependent. Research suggests that indomethacin tends to cause more side effects than other NSAIDs .
The lowest effective dose for the shortest duration possible should be used to minimize risks.
Some common side effects include :
- Stomach discomfort
Some rare but serious side effects include :
- Hearing changes
- Mental changes
- Difficulty swallowing
- Trouble breathing
- Visual changes
The FDA highlights several warnings about indomethacin :
- NSAIDs can increase the risk of potentially fatal heart attacks and strokes
- NSAIDs can increase the risk of stomach injury, including ulcers, bleeding, and potentially fatal perforation
Indomethacin can potentially make certain conditions worse. It should be used with caution in those that have :
- High blood pressure
- Heart failure
- A history of stomach ulcers or bleeding
- Kidney disease
Indomethacin should be avoided in the following cases :
- Those that are allergic or hypersensitive to indomethacin or any of its components
- Those that have a history of allergic reactions to aspirin or other NSAIDs
- Those undergoing heart surgery (coronary artery bypass graft surgery)
Pregnancy and Breastfeeding
Due to a lack of clinical research, it’s unclear how indomethacin affects the fetus. Evidence from some animal studies suggests there may be some negative effects. Indomethacin should only be used during pregnancy if a doctor determines that the benefits outweigh the risks .
Generally speaking, pregnant women should avoid taking indomethacin during the third trimester. It may cause premature closure of an important blood vessel in the baby. However, indomethacin is sometimes used during labor to prevent premature birth [34, 1].
According to research, a small amount of indomethacin is transferred through breast milk. It’s unclear if this small amount affects the baby. Indomethacin should only be used during breastfeeding if a doctor determines that the benefits outweigh the risks .
The following drugs have been reported to interact with indomethacin. However, this is not a complete list, let your doctor know of all the medications you are currently taking to avoid any unexpected interactions.
- Other NSAIDs (such as aspirin, ibuprofen, naproxen, and others)
- Blood thinners (such as warfarin)
- Blood pressure medications
Dosage Forms and Doses
The dosing of indomethacin can vary. Always take this medication as directed by a doctor.
Indomethacin is available in a number of forms, including capsules, extended-release capsules, IV injections, liquid suspension, and suppositories.
Generally, both the effectiveness and side effects depend on the dose. Indomethacin is quickly and completely absorbed in the stomach. It should be taken with food if upset stomach occurs .
Dosage can vary depending on the reason for treatment. In general, the lowest effective dose for the shortest duration possible should be used to minimize side effects.
For arthritis-related conditions, doses typically range from 75 to 150 mg each day, which is taken in divided doses .
Takeaway: Indomethacin is an NSAID that is used to reduce pain and inflammation in several arthritis-related conditions. It is also used to help relieve specific types of headaches that rarely respond to other similar NSAID drugs. However, indomethacin is also associated with a greater frequency of side effects compared to other similar NSAIDs.
Indomethacin can reduce severe pain from inflammatory and autoimmune conditions, such as rheumatoid arthritis, back pain, and chronic spine inflammation. It also helps relieve specific types of headaches that rarely respond to other similar NSAID drugs.
However, indomethacin has several drawbacks. It causes more side effects than similar drugs like Advil (ibuprofen) that work just as well. It can also interfere with labor and should not be used by pregnant women in the third trimester. Some people are allergic to this drug, while others may not respond to it at all. Various natural alternatives can provide safe and effective pain relief in the long run, especially if you have mild symptoms or are looking for an additional remedy with few side effects. Fish oil,
Boswellia, and ginger are just a couple of powerful supplements that may provide you with dual action: pain reduction and enhanced antioxidant defense, especially when combined with lifestyle changes and a healthy diet.