Major
Probable
Description
Spironolactone increases renal lithium reabsorption by promoting distal tubular sodium retention, leading to lithium toxicity.
Mechanism
Spironolactone antagonizes aldosterone-mediated distal tubular sodium excretion; the resulting sodium retention reduces compensatory proximal tubular sodium (and lithium) reabsorption variably, but overall lithium levels tend to rise.
Clinical Significance
Lithium toxicity has been documented with spironolactone co-administration; the direction and magnitude of interaction is variable.
Management
Monitor lithium levels within 1 week of spironolactone initiation or dose change; adjust lithium dose based on levels.