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Contraindicated combination: Related to glibenclamide: Miconazole (systemic route, oromucosal gel): Increase in the hypoglycaemic effect with possible onset of hypoglycaemic manifestations, or even coma (see Contraindications).
Combinations not recommended: Related to sulphonylurea(s): Alcohol: Antabuse effect (intolerance to alcohol), notably for chlorpropamide, glibenclamide, glipizide, tolbutamide.
Increase of the hypoglycaemic reaction (inhibition of compensation reactions), which may facilitate the onset of a hypoglycaemic coma (see Precautions).
Avoid consumption of alcohol and alcohol-containing medications.
Phenylbutazone (systemic route): Increase in the hypoglycaemic effect of sulphonylurea(s) (displacement of sulphonylurea(s) from protein-binding sites and/or decrease in their elimination). Preferably use another anti-inflammatory agent exhibiting fewer interactions, or else warn the patient and step up self-monitoring; if necessary, adjust the dosage during treatment with the anti-inflammatory agent and after its withdrawal.
Related to all antidiabetic agents: Danazol: If the combination cannot be avoided, warn the patient and step up self-monitoring of blood glucose. Possibly adjust the dosage of the antidiabetic treatment during treatment with danazol and after its withdrawal.
Related to metformin: Alcohol: Alcohol intoxication is associated with an increased risk of lactic acidosis during acute alcoholic intoxication, particularly in cases of fasting (see Precautions) or malnutrition and hepatic impairment.
Avoid drinking alcoholic beverages and taking drugs that contain alcohol.
Combinations requiring precautions: Related to all antidiabetic agents: Chlorpromazine: At high dosages (100 mg per day of chlorpromazine), elevation in blood glucose (reduction in release of insulin).
Precaution for use: warn the patient and step up self-monitoring of blood glucose. Possibly adjust the dosage of the antidiabetic during treatment with the neuroleptic and after its withdrawal.
Corticosteroids (glucocorticoids) and tetracosactides (systemic and local routes): Elevation in blood glucose, sometimes accompanied by ketosis (decreased carbohydrate tolerance with corticosteroids).
Precaution for use: warn the patient and step up self-monitoring of blood glucose. Possibly adjust the dosage of the antidiabetic during treatment with corticosteroids and after their withdrawal.
β2-agonists: Elevation in blood glucose due to the β2-agonists.
Precaution for use: warn the patient, step up blood glucose monitoring and possibly transfer to insulin therapy.
Angiotensin converting enzyme inhibitors (e.g. captopril, enalapril): ACE inhibitors may decrease the blood glucose levels. If necessary, adjust the dosage of Glucovance during therapy with an ACE inhibitor and upon its discontinuation.
Related to metformin: Diuretics: Lactic acidosis due to metformin triggered by any functional renal insufficiency, related to diuretics and more particularly to loop diuretics.
Iodinated contrast materials: Intravascular administration of iodinated contrast materials may lead to renal failure. This may induce metformin accumulation and may expose to lactic acidosis. Depending on the renal function, Glucovance must be discontinued 48 hours before the test or at the time of the test and not reinstituted until 48 hours afterwards, and only after renal function has been re-evaluated and found to be normal.
Organic cation transporters (OCT): 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 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.
Related to glibenclamide: Beta-blockers: All beta-blockers mask some of the symptoms of hypoglycaemia: palpitations and tachycardia; Most non-cardioselective beta-blockers increase the incidence and severity of hypoglycaemia.
Warn the patient and step up blood glucose self-monitoring, especially at the start of treatment.
Fluconazole: Increase in the half-life of sulphonylurea with possible onset of hypoglycaemic manifestations.
Warn the patient and step up blood glucose self-monitoring, and possibly adjust the dosage of the antidiabetic treatment during treatment with fluconazole and after its withdrawal.
Bosentan: Risk of decreased hypoglycaemic effect of glibenclamide because bosentan reduces the plasma concentration of glibenclamide. An increased risk of liver enzyme elevations was reported in patients receiving glibenclamide concomitantly with bosentan.
Warn the patient, set-up monitoring of glycaemia and liver enzymes and adjust the dosage of the antidiabetic treatment if necessary.
Bile acid sequestrants: When co-administered simultaneously the plasma concentration of glibenclamide is reduced which may lead to a reduced hypoglycaemic effect. This effect was not observed if glibenclamide is given in a certain period of time before taking the other medicine. It is recommended that Glucovance should be administered at least 4 hours prior a bile acid sequestrant.
Other interaction: combination to be taken into account: Related to glibenclamide: Desmopressin: Reduction in antidiuretic activity.
Colesevelam: When co-administered simultaneously the plasma concentration of glibenclamide is reduced which may lead to a reduced hypoglycaemic effect. This effect was not observed when glibenclamide is given in time lag. It is recommended that Glucovance should be administered at least 4 hours prior colesevelam.
