Major
Established
Description
Thiazide diuretics increase lithium reabsorption in the proximal renal tubule, reliably causing lithium toxicity without dose adjustment.
Mechanism
Thiazides inhibit sodium reabsorption in the distal tubule, triggering compensatory proximal reabsorption of sodium and lithium; plasma lithium levels typically increase by 25–50%.
Clinical Significance
This is a well-established, clinically significant interaction; lithium toxicity case series commonly involve thiazide initiation.
Management
Reduce lithium dose by approximately 25–50% when starting a thiazide; monitor levels within 5–7 days of initiation and regularly thereafter.