Indomethacin
Mechanism :
Indomethacin is a non-steroidal anti-inflammatory drug (NSAID) that exhibits, antipyretic and analgesic properties. Its mode of action, like that of other anti-inflammatory drugs, is not known.
Indication :
- Pain
- Inflammatory/Rheumatoid Disorders
- PDA closure in neonate’s especially preterm
- Nephrogenic diabetes insipidus
Contraindications :
Contraindicated in patients with known hypersensitivity to indomethacin or the excipients, in patients with active peptic ulceration, in patients who have experienced asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs. Severe, rarely fatal, anaphylactic/anaphylactoid reactions to NSAIDs have been reported in such patients. Also contraindicated for the treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery. Suppositories are contraindicated in patients with a history of proctitis or recent rectal bleeding.
Dosing :
Pain/Inflammation in rheumatic disease and nephrogenic diabetes insipidus:
Under 2 years:
Safety and efficacy not established.
2-14 years:
1-2 mg/kg/day in 2-4 oral divided doses; max: 4 mg/kg/day or 1.5-2 g/day.
Above 14 years:
25-50 mg as an intermittent release preparation given either orally or rectally 3-4 times a day; Max: 0.2 g/day OR 75-150 mg/day as an extended release preparation given orally either as a single dose or two divided doses; max: 150 mg/day.
Closure of PDA:
3 IV doses at 12-24 hours intervals. 1st dose is for 200 mcg/kg given intravenously over 20-30 minutes and 2 other doses depending on postnatal age.
For the age group <48 hours:
2nd and 3rd doses are 100 microgram/dose given intravenously over 20-30 minutes at intervals 12 and 24 hours.
For neonates 2-7 days:
2nd and 3rd doses are 200 microgram/dose given intravenously over 20-30 minutes at intervals 12 and 24 hours.
For neonates >7 days:
2nd and 3rd doses are 250 microgram/dose given intravenously over 20-30 minutes at intervals 12 and 24 hours.
Adverse Effect :
Gastrointestinal discomfort, nausea, diarrhea, occasionally bleeding and ulceration, headache, transient renal insufficiency, jaundice and elevated liver function test, dizziness, vertigo, fluid retention, hypersensitivity reactions like bronchospasm, rashes, local discomfort, burning or itching, bleeding, depression, behavioural changes.
Interaction :
ACE-inhibitors: NSAIDs may diminish the antihypertensive effect of ACE-inhibitors. This interaction should be given consideration in patients taking NSAIDs concomitantly with ACE-inhibitors.
Diuretics: Can reduce the natriuretic effect-of furosemide and thiazides in some patients. This response has been attributed to inhibition of renal prostaglandin synthesis.
Lithium: When indomethacin and lithium are administered concurrently, subjects should be observed carefully for signs of lithium toxicity.
Methotrexate: Enhances the toxicity of methotrexate. Caution should be used when NSAIDs are administered concomitantly with methotrexate.
Warfarin: Effects of warfarin and NSAIDs on GI bleeding are synergistic, such that the users of both drugs together have a risk of serious GI bleeding higher than users of either drug alone.
Renal Dose :
Dose in Renal Impairment GFR (mL/min)
20-50 | Dose as in normal renal function, but avoid if possible |
10-20 | Dose as in normal renal function, but avoid if possible |
<10 | Dose as in normal renal function, but only use if CKD 5 and on dialysis |
Dose in Patients undergoing Renal Replacement Therapies
CAPD | Not dialysed. Dose as in normal renal function. |
HD | Not dialysed. Dose as in normal renal function. |
HDF/High flux | Unlikely to be dialysed. Dose as in normal renal function |
CAV/VVHD | Not dialysed. Dose as in GFR=10– 20 mL/min |
Hepatic Dose :
Dosage reduction may be necessary in patients with hepatic dysfunction. Close monitoring and periodic assessment of liver function is recommended in children.