Side Effects of Indocin (indomethacin)

Indocin (indomethacin) is a nonsteroidal anti-inflammatory drug (NSAID) that reduces fever, pain and inflammation caused by osteoarthritis, rheumatoid arthritis, gouty arthritis or ankylosing spondylitis. Indocin works by reducing the production of prostaglandins. 

Prostaglandins are chemicals that the body produces and which cause the fever and pain that are associated with inflammation. Indomethacin blocks the enzymes that make prostaglandins (cyclooxygenase 1 and 2) and thereby reduces the levels of prostaglandins. As a result, fever, pain and inflammation are reduced. 

Common side effects of Indocin include

• nausea,
• vomiting,
• diarrhea,
• stomach discomfort,
• heartburn,
• rash,
• headache,
• dizziness and
• drowsiness.

Serious side effects of Indocin include

• fluid retention,
• blood clots,
• heart attacks,
• high blood pressure (hypertension),
• heart failure,
• ulceration of the stomach or intestine,
• reduced ability of blood to clot thereby increasing bleeding after an injury, and
• impaired kidney function.

Drug interactions of Indocin include cholestyramine and colestipol, which may decrease absorption of Indocin by binding to Indocin in the intestine and preventing absorption into the body.

• Indocin and other NSAIDs may decrease the elimination of lithium by the kidneys and, therefore, increase the blood level of lithium, which could lead to lithium toxicity.
• Indocin may interfere with the blood pressure-lowering effects of drugs that are given to reduce blood pressure.
• When Indocin is used in combination with methotrexate or aminoglycosides the blood levels of the methotrexate or aminoglycoside may increase, which may lead to more methotrexate or aminoglycoside-related side effects.
• Indocin should be avoided by patients with a history of asthma attacks, hives or other allergic reactions to aspirin or other NSAIDs.
  • If aspirin is taken with Indocin there may be an increased risk for developing an ulcer.
  • Persons who have more than 3 alcoholic beverages per day may be at increased risk of developing stomach ulcers when taking Indocin or other NSAIDs.
• Indocin increases the negative effect of cyclosporine on kidney function and reduces the effect of furosemide and thiazide diuretics because of prostaglandin inhibition.
• Individuals taking oral blood thinners or anticoagulants should avoid Indocin because Indocin also thins the blood, and excessive blood thinning may lead to bleeding. 

Use of Indocin during pregnancy has not been adequately studied. Indocin may have adverse effects on the fetus. 

Indocin is excreted in breast milk and therefore should be avoided by breastfeeding mothers.

Common side effects of indomethacin are:

• nausea,
• vomiting,
• diarrhea,
• stomach discomfort,
• heartburn,
• rash,
• headache,
• dizziness and
• drowsiness.

Other important side effects are:

• Fluid retention,
• blood clots,
• heart attacks,
• hypertension (high blood pressure), and
• heart failure.

Some individuals are allergic to NSAIDs and may develop shortness of breath when an NSAID is taken. People with asthma are at a higher risk for experiencing serious allergic reaction to NSAIDs. Individuals with a serious allergy to one NSAID are likely to experience a similar reaction to a different NSAID.

Indomethacin may cause ulceration of the stomach or intestine, and the ulcers may bleed. Sometimes, ulceration may lead to perforation of the intestine and bleeding can occur without abdominal pain, and black tarry stools, weakness, and dizziness upon standing (orthostatic hypotension) may be the only signs of a ulceration.

NSAIDs can reduce the ability of blood to clot thereby increasing bleeding after an injury.

NSAIDs reduce the flow of blood to the kidneys and impair function of the kidneys. The impairment is most likely to occur in patients with preexisting impairment of kidney function or congestive heart failure, and use of NSAIDs in these patients should be done cautiously. Individuals who have nasal polyps or are allergic to aspirin or other NSAIDs should not use indomethacin because there is an increased risk of severe allergic reactions in these individuals.

The following adverse reactions are discussed in greater detail in other sections of the labeling:

• Cardiovascular Thrombotic Events
• GI Bleeding, Ulceration and Perforation
• Hepatotoxicity
• Hypertension
• Heart Failure and Edema
• Renal Toxicity and Hyperkalemia
• Anaphylactic Reactions
• Serious Skin Reactions
• Hematologic Toxicity

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

• In a gastroscopic study in 45 healthy subjects, the number of gastric mucosal abnormalities was significantly higher in the group receiving indomethacin capsules than in the group taking Indocin Suppositories or placebo.
• In a double-blind comparative clinical study involving 175 patients with rheumatoid arthritis, however, the incidence of upper gastrointestinal adverse effects with Indocin Suppositories or indomethacin capsules was comparable. The incidence of lower gastrointestinal adverse effects was greater in the suppository group.
• The adverse reactions for indomethacin capsules listed in the following table have been arranged into two groups:
  •  (1) incidence greater than 1%; and
  • (2) incidence less than 1%.
  • The incidence for group (1) was obtained from 33 double-blind controlled clinical trials reported in the literature (1,092 patients).
  • The incidence for group (2) was based on reports in clinical trials, in the literature, and on voluntary reports since marketing.
  • The probability of a causal relationship exists between indomethacin and these adverse reactions, some of which have been reported only rarely.
• The adverse reactions reported with indomethacin capsules may occur with use of the suppositories. In addition, rectal irritation and tenesmus have been reported in patients who have received the suppositories.

Table 1 Summary of Adverse Reactions for Indomethacin Capsules

Causal Relationship Unknown

Other reactions have been reported but occurred under circumstances where a causal relationship could not be established. However, in these rarely reported events, the possibility cannot be excluded. Therefore, these observations are being listed to serve as alerting information to physicians:

• Cardiovascular: Thrombophlebitis
• Hematologic: Although there have been several reports of leukemia, the supporting information is weak
• Genitourinary: Urinary frequency
• A rare occurrence of fulminant necrotizing fasciitis, particularly in association with Group Aβ hemolytic streptococcus, has been described in persons treated with nonsteroidal anti-inflammatory agents, including indomethacin, sometimes with fatal outcome

See Table 2 for clinically significant drug interactions with indomethacin.

Table 2 Clinically Significant Drug Interactions with Indomethacin

Effects On Laboratory Tests

• Indocin reduces basal plasma renin activity (PRA), as well as those elevations of PRA induced by furosemide administration, or salt or volume depletion.
• These facts should be considered when evaluating plasma renin activity in hypertensive patients.
• False-negative results in the dexamethasone suppression test (DST) in patients being treated with indomethacin have been reported.
• Thus, results of the DST should be interpreted with caution in these patients.