Indomethacin (5 brand names, 5 dosage forms, 3 routes)
Available dosage forms: SUPPOSITORY, CAPSULE, CAPSULE, EXTENDED RELEASE, SUSPENSION, INJECTABLE.
Routes of administration: RECTAL, ORAL, INJECTION.
Brand Names
- INDO-LEMMON
- INDOCIN
- INDOCIN SR
- INDOMETHACIN
- TIVORBEX
Indications and Usage
Indomethacin capsules are indicated for: Moderate to severe rheumatoid arthritis including acute flares of chronic disease Moderate to severe ankylosing spondylitis Moderate to severe osteoarthritis Acute painful shoulder (bursitis and/or tendinitis) Acute gouty arthritis
Contraindications
Indomethacin capsules are contraindicated in the following patients: Known hypersensitivity (e.g., anaphylactic reactions and serious skin reactions) to indomethacin or any components of the drug product [see Warnings and Precautions ( 5.7, 5.9)] . History of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs. Severe, sometimes fatal, anaphylactic reactions to NSAIDs have been reported in such patients [see Warnings and Precautions ( 5.7, 5.8)] . In the setting of coronary artery bypass graft (CABG) surgery [see Warnings and Precautions ( 5.1)].
Adverse Reactions
The following adverse reactions are discussed in greater detail in other sections of the labeling: Cardiovascular Thrombotic Events [see Warnings and Precautions ( 5.1)] GI Bleeding, Ulceration and Perforation [see Warnings and Precautions ( 5.2)] Hepatotoxicity [see Warnings and Precautions ( 5.3)] Hypertension [see Warnings and Precautions ( 5.4)] Heart Failure and Edema [see Warnings and Precautions ( 5.5)] Renal Toxicity and Hyperkalemia [see Warnings and Precautions ( 5.6)] Anaphylactic Reactions [see Warnings and Precautions ( 5.7)] Serious Skin Reactions [see Warnings and Precautions ( 5.9)] Hematologic Toxicity [see Warnings and Precautions ( 5.12)]
Drug Interactions
See Table 2for clinically significant drug interactions with indomethacin. Table 2 Clinically Significant Drug Interactions with Indomethacin Drugs That Interfere with Hemostasis Clinical Impact: Indomethacin and anticoagulants such as warfarin have a synergistic effect on bleeding. The concomitant use of indomethacin and anticoagulants have an increased risk of serious bleeding compared to the use of either drug alone. Serotonin release by platelets plays an important role in hemostasis. Case-control and cohort epidemiological studies showed that concomitant use of drugs that interfere with serotonin reuptake and an NSAID may potentiate the risk of bleeding more than an NSAID alone. Intervention: Monitor patients with concomitant use of indomethacin capsules with anticoagulants (e.g., warfarin), antiplatelet agents (e.g., aspirin), selective serotonin reuptake inhibitors (SSRIs), and serotonin norepinephrine reuptake inhibitors (SNRIs) for signs of bleeding [ see Warnings and Precautions ( 5.12 ) ] . Aspirin Clinical Impact: Controlled clinical studies showed that the concomitant use of NSAIDs and analgesic doses of aspirin does not produce any greater therapeutic effect than the use of NSAIDs alone. In a clinical study, the concomitant use of an NSAID and aspirin was associated with a significantly increased incidence of GI adverse reactions as compared to use of the NSAID alone [ see Warnings and Precautions ( 5.2) ]. Intervention: Concomitant use of indomethacin capsules and analgesic doses of aspirin is not generally recommended because of the increased risk of bleeding [ see Warnings and Precautions ( 5.12)] . Indomethacin capsules are not substitute for low dose aspirin for cardiovascular protection. ACE Inhibitors, Angiotensin Receptor Blockers, and Beta-Blockers Clinical Impact: NSAIDs may diminish the antihypertensive effect of angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), or beta-blockers (including propranolol). In
Mechanism of Action
Indomethacin has analgesic, anti-inflammatory, and antipyretic properties. The mechanism of action of indomethacin capsules, like that of other NSAIDs, is not completely understood but involves inhibition of cyclooxygenase (COX-1 and COX-2). Indomethacin is a potent inhibitor of prostaglandin synthesis in vitro. Indomethacin concentrations reached during therapy have produced in vivoeffects. Prostaglandins sensitize afferent nerves and potentiate the action of bradykinin in inducing pain in animal models. Prostaglandins are mediators of inflammation. Because indomethacin is an inhibitor of prostaglandin synthesis, its mode of action may be due to a decrease of prostaglandins in peripheral tissues.
Overdosage
Symptoms following acute NSAID overdosages have been typically limited to lethargy, drowsiness, nausea, vomiting, and epigastric pain, which have been generally reversible with supportive care. Gastrointestinal bleeding has occurred. Hypertension, acute renal failure, respiratory depression, and coma have occurred, but were rare [ see Warnings and Precautions (5.1, 5.2, 5.4, 5.6) ]. Manage patients with symptomatic and supportive care following an NSAID overdosage. There are no specific antidotes. Consider emesis and/or activated charcoal (60 to 100 grams in adults, 1 to 2 grams per kg of body weight in pediatric patients) and/or osmotic cathartic in symptomatic patients seen within four hours of ingestion or in patients with a large overdosage (5 to 10 times the recommended dosage). Forced diuresis, alkalinization of urine, hemodialysis, or hemoperfusion may not be useful due to high protein binding. For additional information about overdosage treatment contact a poison control center (1-800-222-1222).