Major
Established
Description
NSAIDs markedly increase lithium plasma levels, potentially causing lithium toxicity (tremor, ataxia, confusion, cardiac arrhythmias).
Mechanism
Lithium is renally excreted in parallel with sodium; NSAID-induced sodium retention reduces renal lithium clearance, raising serum lithium to potentially toxic levels.
Clinical Significance
Lithium levels can increase 15–66% within days of NSAID initiation; toxicity at levels >1.5 mEq/L can cause irreversible neurological damage.
Management
Avoid NSAIDs in lithium-treated patients; use acetaminophen for pain. If NSAID is essential, check lithium levels within 3–5 days and adjust dose. Sulindac may be safer (less effect on renal prostaglandins).