Indomethacin inhibits prostaglandin synthesis by decreasing the activity of the enzyme cyclooxygenase , which results in decreased formation of prostaglandin precursors from arachidonic acid.

Rheumatoid arthritis ; Osteoarthritis ; Ankylosing spondylitis ; Juvenile arthritis; Psoriatic arthritis ; Reiter's disease ; Rheumatic Complications associated with Paget's disease of bone; Acute gouty arthritis; Calcium pyrophosphate deposition disease (pseudogout); Bursitis and tendinitis ; Fever associated with malignancy ; Dysmenorrhea; Prevention and treatment of vascular headaches; Bartter's disease ; Pericarditis.
Drug of first choice in ankylosing spondylitis ; for other indications (except Bartter's syndrome) , recommended only for patients unresponsive to less toxic NSAIDs or , in the case of fever , to other antipyretic agents.

a- >10% : Headache
b- 1% to 10% : Dizziness; Drowsiness ; Fatigue; Depression ; Malaise ; Nausea; Abdominal pain , cramps, distress ; Anorexia ; GI bleeding ;Heartburn; Indigestion ; Constipation ; Diarrhea ; Inhibition of platelet aggregation ; Tinnitus
c- <1% : Anaphylaxis ; Agranulocytosis ; Thrombocytopenia; Arrhythmia; Aseptic meningitis ; Bronchospasm; Cholestatic jaundice ; CHF; Erythema multiforme ; Exfoliative dermatitis ; Toxic epidermal necrolysis ; Urticaria ; Hemolytic anemia; Hepatitis ; Hypertension ; Hypoglycemia ; Interstitial nephritis; Nephrotic syndrome ; Peripheral neuropathy; Proctitis ; Psychosis ; Hallucination ; Renal failure; Retinal/ macular disturbances; Toxic amblyopia.

Hypersensitivity to indomethacin , any component of the formulation , aspirin , or other NSAIDs ; Patients in whom asthma , urticaria , or rhinitis are precipitated by NSAIDs/ aspirin ; Active GI bleeding or ulcer disease ; Premature neonates with necrotizing enterocolitis; Impaired renal function ; Active bleeding ; Thrombocytopenia ; Pregnancy ( 3 rd trimester).

Use with caution in patients with CHF , hypertension , dehydration , decreased renal or hepatic function , history of GI disease (bleeding or ulcers) , or those receiving anticoagulants.
Elderly are at a high risk for adverse effects from NSAIDs ; therefore , use lowest effective dose for shortest period possible . Discontinue if signs/ symptoms of hepatic injury occur . Use with caution in patients with depression or other psychiatric disorder, epilepsy , or parkinsonism ; discontinue if severe CNS adverse effects occur . Withhold for at least 4-6 half – lives prior to surgical or dental procedures .

Concurrent use with indomethacin may decrease the antihypertensive effects of ACE inhibitors , angiotensin II antagonists , loop diuretics , thiazides and hydralazine . Anticoagulants (warfarin , heparin , LMWHs) and antiplatelet drugs (ticlopidine, clopidogrel , aspirin , dipyridamole ) can cause an increased risk of bleeding . Cholestyramine and colestipol reduce the bioavailability of some NSAIDs ; separate administration times . Corticosteroids may increase the risk of GI ulceration ; avoid concurrent use . NSAIDs may increase serum creatinine , potassium , blood pressure , and cyclosporine levels ; monitor cyclosporine levels and renal function carefully . Indomethacin may increase the levels / effects of amiodarone , fluoxetine , phenytion , rosiglitazone , pioglitazone , sertraline , and warfarin . Litium levels can be increased ; avoid concurrent use if possible or monitor lithium levels and adjust dose. Avoid use NSAIDs during moderate or high – dose methotrexate (increased and prolonged methotrexate levels ). Concurrent use with potassium – sparing diuretics may cause hyperkalemia . Concurrent use with zidovudine not recommended ; toxicity of either or both of the medications may be increased. Caution also recommended with aminoglycosides and digitalis glycosides ; indomethacin has caused increased plasma concentrations of these medications in infants.

Monitor renal function (serum creatinine , BUN) ; Observe for bleeding ; CBC ; Liver function tests

Oral dosage forms of indomethacin should always be administered after meals or with food or antacid to reduce GI irritation.

• Capsule:
  
  Usual adult dose:
  Antirheumatic (nonsteroidal anti – inflammatory ) – Oral , initially 25 or 50 mg 2 to 4 times a day ; if well tolerated , the dosage per day may be increased by 25 or 50 mg at weekly intervals until a satisfactory response is obtained or up to a maximum dose of 200 mg per day. After a satisfactory response has been achieved , dosage should be reduced to the lowest dose that provides continuing control of symptoms .
  In acute flare –ups of rheumatoid arthritis , dosage may be increased by 25 or 50 mg daily , as needed and tolerated.
  For those arthritic patients who have persistent night pain and/ or morning stiffness, up to 100 mg of the total daily dose may be given at bedtime.
  Antigout– Oral , 100 mg initially , then 50 mg 3 times a day until pain is relieved , with the dosage then being reduced until medication is discontinued.
  Anti- inflammatory ( nonsteroidal) – Oral , 75 to 150 mg per day in three or four divided doses.
  Antipyretic– Oral , 25 or 50 mg 3 or 4 times a day.
  
  Usual adult prescribing limits:
  Antirheumatic (nonsteroidal anti – inflammatory ) – Oral , 1.5 to 2.5 mg per kg of body weight per day , administered in 3 or 4 divided doses , up to a maximum of 4 mg per kg of body weight per day or 150 to 200 mg per day , whichever is less. After a satisfactory response has been obtained , dosage should be reduced to the lowest dose that provides continuing control of symptoms.
  
  
• Suppository:
  
  Usual adult dose:
  Antirheumatic ( nonsteroidal anti – inflammatory ) ; Anti – inflammatory (nonsteroidal) ; Antigout agent ; Antipyretic – Rectal , 50 mg up to 4 times a day.
  For those arthritic patients who have persistent night pain and/ or morning siffness, up to 100 mg of the total daily dose may be given at bedtime.
  
  Usual adult prescribing limits:
  Rectal or combined oral and rectal , 200 mg per day.
  To ensure maximum absorption , the suppository should be retained for at least one full hour after insertion .
  

• Capsule: 25 mg
• Suppository: 100 mg

• USP DI, 2004
• Up To Date, Vol. 13.1 (2005)
• Martindale, The Complete Drug Reference, 33 rd edition 2002