Glucovance Drug Interactions

Contraindicated combination: Related to glibenclamide: Miconazole (systemic route, oromucosal gel): Increase in the hypoglycemic effect with possible onset of hypoglycemic manifestations, or even coma.
Related to metformin: Iodinated contrast media: 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, metformin + glibenclamide (Glucovance) must be discontinued 48 hours before or from the time of intravascular administration of iodinated contrast media and not reinstituted until 48 hours afterwards, and only after renal function has been re-evaluated and found to be normal.
Combinations not recommended: Related to sulfonylureas: Alcohol: An antabuse syndrome (intolerance to alcohol) has occurred very rarely following the concomitant use of alcohol and glibenclamide. This effect has also been reported with chlorpropamide, glipizide and tolbutamide. Alcohol ingestion may increase the hypoglycemic action (via inhibition of compensation reactions or delaying its metabolic inactivation), which may facilitate the onset of a hypoglycemic coma. Avoid consumption of alcohol and alcohol-containing medications.
Phenylbutazone (systemic route): Increase in the hypoglycemic effect of sulfonylureas (displacement of sulfonylureas 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 glibenclamide: Bosentan: There is an increased risk of hepatoxicity if bonsentan is given with glibenclamide and it is recommended that such be avoided; the hypoglycemic effect of glibenclamide may also be reduced.
Related to metformin: Alcohol: Increased in risk of lactic acidosis during alcoholic intoxication, particularly in cases of fasting or malnutrition and hepatocellular failure. Avoid drinking alcoholic beverages and taking drugs that contain alcohol.
Combinations requiring precautions: Related to all antidiabetic agents: 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.
Related to metformin: Diuretics: Lactic acidosis due to metformin triggered by any functional renal insufficiency, related to diuretics and more particularly to loop diuretics.
Organic cation transporters (OCT): Metformin is a substance 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 hypoglycemia such as palpitations and tachycardia. Most non-cardioselective beta-blockers increase the incidence and severity of hypoglycemia. Warn the patient and step up blood glucose self-monitoring, especially at the start of treatment.
Clonidine, reserpine, guanethidine or sympathomimetics: These substances may mask the warning symptoms of a hypoglycemic attack. Warn the patient and step up blood glucose self-monitoring, especially at the start of treatment.
Fluconazole: Increase in the half-life of sulfonylurea with possible onset of hypoglycemic manifestations. Warn the patient and step up blood glucose self-monitoring, and possibly adjust the dosage of the antidiabetic during treatment with fluconazole and after its withdrawal.
Desmopressin: Reduction in antidiuretic effect of desmopressin.
Colesevelam: When co-administered simultaneously the plasma concentration of glibenclamide is reduced which may lead to a reduced hypoglycemic effect. This effect was not observed when glibenclamide is given in time lag. It is recommended that metformin + glibenclamide (Glucovance) should be administered at least 4 hours prior to colesevelam.
Angiotensin converting enzyme inhibitors (e.g. captopril, enalapril): ACE inhibitors may decrease the blood glucose levels. If necessary adjust the dosage of metformin + glibenclamide (Glucovance) during therapy with an ACE inhibitor and upon its discontinuation.