Indomethacin is a potent non-steroidal anti-inflammatory drug (NSAID) used to treat rheumatoid arthritis, osteoarthritis, acute gout, and fever. It has a more pronounced adverse effect profile than other NSAIDs.
Also known as: indometacin, indocin, indomethacin
NSAID + glycopeptide: additive nephrotoxicity. Both are potentially nephrotoxic.
Indomethacin reduces renal blood flow while vancomycin is directly nephrotoxic. The combination increases the risk of acute renal failure.
Creatinine, GFR, urine volume.
Creatinine >2x baseline, anuria.
Monitor renal function (creatinine, GFR) before and during treatment. Maintain adequate hydration.
DailyMed/FDA — approved Indomethacin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d2997707-1541-4f5d-8c8d-70b0a13be8b2
NSAID + lithium: lithium levels increased 15-30%. Risk of lithium toxicity (tremor, confusion, seizures).
Indomethacin has the greatest effect on lithium levels among NSAIDs. The main mechanism is reduced renal lithium clearance via inhibition of prostaglandin E2 in the kidney. Prostaglandins regulate renal blood flow and tubular reabsorption — their inhibition reduces lithium excretion by 15-30%. The effect is dose-dependent and most pronounced during the first 5-7 days of concomitant treatment. Other NSAIDs (ibuprofen, naproxen) also increase lithium levels, but to a lesser degree (5-15%). Lithium toxicity initially manifests with fine tremor, nausea, and diarrhoea, progressing to confusion, ataxia, and seizures. The therapeutic window of lithium is narrow (0.6-1.2 mEq/L), so small changes can have significant clinical consequences.
NSAID + lithium: lithium levels increased 15-30%. Risk of lithium toxicity (tremor, confusion, seizures). Monitor lithium levels weekly.
Indomethacin reduces renal clearance of lithium, increasing serum levels. The effect is more pronounced with indomethacin than other NSAIDs. Toxicity can be severe.
Lithium levels, signs of toxicity (tremor, nausea, confusion, diarrhoea).
Lithium level >1.5 mEq/L, severe neurological signs.
Avoid combination if possible. If necessary, reduce lithium dose by 20-30% and monitor lithium levels weekly during the first 2 weeks.
DailyMed/FDA — approved Indomethacin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d2997707-1541-4f5d-8c8d-70b0a13be8b2
NSAID + antimetabolite: methotrexate renal clearance reduced. Risk of toxicity (myelosuppression, mucositis).
Indomethacin reduces renal blood flow and tubular secretion of methotrexate, which is primarily excreted renally (80-90% unchanged). Reduced clearance can increase methotrexate levels by 20-50%, depending on dose and renal function. High-dose methotrexate (>100 mg/m²) is especially dangerous with NSAIDs — the risk of pancytopenia, severe mucositis, and hepatotoxicity increases significantly. At low doses (10-25 mg/week for arthritis), the risk is lower but remains relevant. Monitor blood count (leukocytes, platelets) and hepatic enzymes.
Potent NSAID + antimetabolite: methotrexate renal clearance reduced. Risk of toxicity (myelosuppression, mucositis, hepatotoxicity).
Indomethacin reduces renal blood flow and tubular secretion of methotrexate, increasing serum levels. Risk of pancytopenia and mucositis.
Blood count, methotrexate levels, signs of mucositis.
Pancytopenia, severe mucositis, neutrophils <500/mm³.
Avoid NSAIDs during high-dose methotrexate. If necessary, monitor blood count weekly and methotrexate levels.
DailyMed/FDA — approved Indomethacin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d2997707-1541-4f5d-8c8d-70b0a13be8b2
Food delays absorption (capsules: peak from 1-2 h to 2-4 h). Oral suspension: faster absorption.
Take with food to reduce GI discomfort. Prefer oral suspension if available.
Direct nephrotoxicity. High risk of acute renal failure, especially in the elderly.
Avoid in renal impairment. If necessary, monitor GFR closely.
DailyMed/FDA — approved Indomethacin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d2997707-1541-4f5d-8c8d-70b0a13be8b2
CONTRAINDICATED in 3rd trimester (ductus arteriosus closure). Used intentionally to close ductus in premature infants.
3rd trimester: CONTRAINDICATED (except therapeutic duct closure). 1st-2nd trimester: avoid.
Excreted in breast milk. Avoid during breastfeeding.
May affect female and male fertility.
DailyMed/FDA — approved Indomethacin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d2997707-1541-4f5d-8c8d-70b0a13be8b2
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Very potent NSAID. Non-selectively inhibits COX-1 and COX-2. Anti-inflammatory, analgesic, and antipyretic activity. Used in acute gout and inflammatory conditions.
Non-selective and competitive inhibition of COX-1 and COX-2. Anti-inflammatory potency superior to most NSAIDs. Also acts by inhibiting polymorphonuclear motility.
Rapid and almost complete oral absorption. Bioavailability: 100%. Peak: 1-2 h (capsules), 2-4 h (suspension). Food delays absorption.
Metabolised in the liver by CYP2C9 and demethylation (CYP to metabolites). Active metabolites (indometacin and indomethacin acid). Renal excretion (60%) and biliary (33%).
4.5 h (capsules). Active metabolites prolong effect (effective half-life: 10-11 h).
Medicines from the same therapeutic group (ATC classification) or the same pharmacological class.
