lithium and ibuprofen

Ibuprofen inhibits renal prostaglandin synthesis, which reduces renal blood flow and glomerular filtration rate. This decreases the renal clearance of lithium, leading to increased serum lithium concentrations. The effect is primarily pharmacodynamic at the renal level, with a pharmacokinetic consequence of reduced lithium excretion.

Co-administration can raise serum lithium levels by 15% to 60%, potentially causing lithium toxicity. Early signs include nausea, vomiting, diarrhoea, coarse tremor, and lethargy; severe toxicity can lead to confusion, ataxia, seizures, and cardiac arrhythmias. The onset is usually within days of starting the NSAID, but may be delayed.

Avoid concurrent use where possible, particularly in patients with pre-existing renal impairment or those receiving long-term lithium therapy. If ibuprofen is necessary, use the lowest effective dose for the shortest duration. Monitor serum lithium levels at baseline, then after 3 to 7 days of starting ibuprofen, and periodically thereafter. Monitor renal function (creatinine, eGFR) and signs of toxicity. Adjust lithium dose as needed and recheck levels after any change.

This interaction is well established and widely documented in clinical guidelines and pharmacology references. It is supported by numerous case reports, pharmacokinetic studies, and clinical trials. The magnitude of effect varies between individuals, but the risk of clinically significant toxicity is consistently recognised.