Metformin-Cimetidine Drug Interaction and Risk of Lactic Acidosis in Renal Failure: A Pharmacovigilance-Pharmacokinetic Appraisal

Study found an increase in the percentage of patients with renal failure reporting lactic acidosis associated with metformin combined with cimetidine at conventional doses, following approval of metformin for use in mild-moderate renal failure in 2016.

SPS commentary:

With physiologically based pharmacokinetic simulation for metformin (1g BD) with cimetidine (300 mg QDS. or 400 mg BD.) in stage 1 of chronic kidney disease, metformin (1g BD) with cimetidine (300 mg QDS or 400 mg BD or 800 mg OD.) in stage 2, and most combinations in stage 3, the peak plasma metformin concentrations exceeded the 3 mg/L threshold.

Diabetes Care