Metformin-Cimetidine Drug Interaction and Risk of Lactic Acidosis in Renal Failure: A Pharmacovigilance-Pharmacokinetic Appraisal
Authors' conclusion
Metformin combined with cimetidine at conventional doses may cause LA in patients with mild-to-moderate RF.
Study context
- Population
- FAERS reports of lactic acidosis (LA) associated with metformin, overall population and patients with renal failure; Physiologically based pharmacokinetic (PBPK) simulations in patients with various degrees of renal failure (RF)
- Comparison
- Metformin combined with H2 receptor inhibitors (H2RI) vs metformin alone
- Outcome
- LA risk signal (disproportionality); peak plasma metformin concentration vs 3 mg/L threshold (PBPK)
Methodological detailsFDA Adverse Event Reporting System data (2012Q4 to 2022Q4), disproportionality analysis, PBPK simulation
- FDA Adverse Event Reporting System data (2012Q4 to 2022Q4)
- Disproportionality analysis
- PBPK simulation
Main finding
As reported in the abstract
- Reported LA risk signal associated with metformin and cimetidine in the overall population within the study timeframe only
- Peak plasma metformin concentration exceeded 3 mg/L threshold: metformin 1,000 mg b.i.d. with cimetidine 300 mg q.i.d. or 400 mg b.i.d. in CKD stage 1; with cimetidine 300 mg q.i.d., 400 mg b.i.d. or 800 mg q.d. in stage 2; most combinations in stage 3
Further findings
Percentage of patients with RF reporting LA with metformin + H2RI · after the 2016 FDA metformin approval for mild-to-moderate RF
- Increased
Original publication
Metformin-Cimetidine Drug Interaction and Risk of Lactic Acidosis in Renal Failure: A Pharmacovigilance-Pharmacokinetic Appraisal. Diabetes Care. Published 10 November 2023. doi:10.
Composed by AI from the published abstract and checked against it. How Briefs are made →