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Contraindicated combinations: In patients with CrCL below 45 mL/min or eGFR below 45 mL/min/1.73 m2 for intravenous administration or in patients with CrCL below 45 mL/min or eGFR below 60 mL/min/1.73 m2 for intra-arterial administration of iodinated contrast materials, metformin must be discontinued 48 hours before the test (see Contraindications).
Combinations to be used with caution: Medicinal products with intrinsic hyperglycemic activity (e.g. glucocorticoids and tetracosactides [systemic and local routes], beta-2-agonists, danazol, and chlorpromazine at high dosages of 100 mg per day, diuretics): More frequent blood glucose monitoring may be required, especially at the beginning of treatment. If necessary, adjust the metformin dosage during therapy with the respective medicinal product and upon its discontinuation. Diuretics, especially loop diuretics, may increase the risk of lactic acidosis due to their potential to decrease renal function (further to their intrinsic hyperglycemic effect).
Organic cation transporters (OTC): Metformin is a substrate of both transporters OCT1 and OCT2. Co-administration of metformin with Substrates/inhibitors of OCT1 (such as verapamil) may reduce efficacy of metformin; Inducers of OCT1 (such as rifampicin) may increase gastrointestinal absorption and efficacy; Substrates/inhibitors of OCT2 (such as cimetidine, dolutegravir, crizotinib, olaparib, daclatasvir, vandetanib) may decrease the renal elimination of metformin and thus lead to an increase in metformin plasma concentration.
Therefore, caution is advised when these drugs are co-administered with metformin and a dose adjustment may be considered, particularly in patients with renal impairment.
Interaction with alcohol: The risk of lactic acidosis is increased in acute alcohol intoxication, particularly in case of fasting or malnutrition or hepatic insufficiency. It is recommended that consumption of alcohol and alcohol-containing medicinal products be avoided.
