Glucovance

2nd-line therapy in type 2 diabetes when diet, exercise & initial treatment w/ sulfonylurea or metformin do not result in adequate glycemic control.

Adult Individualized dosage. Max recommended daily dose: Metformin 2,000 mg/glibenclamide 20 mg. 2nd-line therapy Initially 500 mg/5 mg bd. Daily dose should be titrated in increments of not >500 mg/5 mg up to min effective dose to achieve adequate control of blood glucose or to max dose of 2,000 mg/20 mg daily.

Should be taken with food.

Hypersensitivity to metformin HCl, glibenclamide or other sulphonylurea & sulphonamide. Type I diabetes, diabetic pre-coma. Any type of acute metabolic acidosis (eg, lactic acidosis or diabetic ketoacidosis). Acute or chronic diseases which may cause tissue hypoxia (eg, cardiac or resp failure, recent MI, shock). Porphyria. In association w/ miconazole. Discontinue use 48 hr prior to elective major surgery & may not be reinstituted until 48 hr afterwards & only after renal function has been re-evaluated & found to be normal. Renal disease or dysfunction (CrCl <60 mL/min). Acute conditions w/ potential to alter renal function (eg, dehydration, severe infection, shock). Hepatic insufficiency, acute alcohol intoxication, alcoholism. Lactation.

Not to be used as initial therapy due to increased risk of hypoglycemia. Risk of lactic acidosis. Temporarily discontinue use in case of dehydration. Concomitant use w/ medicinal products that can acutely impair renal function (eg, antihypertensives, diuretics & NSAIDs). Increased risk of CV mortality. Consider other antidiabetic treatment options if patient encounters repeated episodes of hypoglycaemia. Correct moderate hypoglycemic symptoms w/o loss of consciousness or neurological manifestations by immediate sugar intake. Possible severe hypoglycaemic reactions w/ coma, seizures or other neurological signs & constitute medical emergency requiring immediate treatment w/ IV glucose once cause is diagnosed or suspected. Possible haemolytic anemia. Patients w/ G6PD-deficiency. Concomitant use w/ medications affecting renal function or may interfere metformin disposition (eg, cationic drugs). Intravascular administration of iodinated contrast agents may lead to contrast-induced nephropathy; discontinue use prior to or at the time of imaging procedure & not to be restarted until at least 48 hr after, provided that renal function has been re-evaluated & found to be stable. Promptly discontinue use when hypoxic states occur. Possible blood sugar imbalance. Excessive alcohol intake. Monitor vit B₁₂ serum levels annually; increased risk of low vit B₁₂ levels w/ increasing metformin dose, treatment duration &/or in patients w/ risk factors known to cause vit B₁₂ deficiency. Promptly evaluate for evidence of ketoacidosis or lactic acidosis in patients w/ type 2 diabetes previously well-controlled on metformin who develops lab abnormalities or clinical illness; immediately stop use & initiate other appropriate corrective measure if acidosis of either form occurs. Contains lactose; contraindicated in case of congenital galactosemia, glucose & galactose malabsorption syndrome or lactase deficiency. Periodically perform fasting blood glucose & HbA_1c measurements. Perform initial & periodic monitoring of hematologic parameters & renal function at least on an annual basis. Exclude vit B₁₂ deficiency if megaloblastic anemia is suspected. Renal & hepatic impairment. Alert patients to hypoglycaemia symptoms; may affect ability to drive or use machines. Not recommended for use during pregnancy. Not to be used in childn & elderly.

Upper resp infection, headache, GI reactions (eg, diarrhea, nausea/vomiting, abdominal pain), dizziness. Hypoglycemia. Taste disturbance; vit B₁₂ deficiency.

May lead to loss of blood glucose control w/ thiazides & other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, OCs, phenytoin, nicotinic acid, sympathomimetics, Ca channel blockers & INH. Avoid consumption of alcohol & alcohol-containing medications. Increased hypoglycaemic effect w/ phenylbutazone. Concomitant use w/ danazol; medicinal products w/ intrinsic hyperglycaemic activity [eg, glucocorticoids, tetracosactides, β₂-agonists & chlorpromazine (high dose; 100 mg/day), diuretics]. May decrease blood glucose levels w/ ACE inhibitors. Glibenclamide: May potentiate hypoglycemic action w/ NSAIDs & other drugs that are highly protein bound, salicylates, sulfonamides, chloramphenicol, probenecid, coumarins, MAOIs, β-adrenergic blockers; ciprofloxacin. Increased hypoglycaemic effect w/ possible onset of hypoglycaemic manifestations or even coma w/ miconazole. May reduce hypoglycaemic effect & increased risk of hepatotoxicity w/ bosentan. Hypoglycaemia symptoms may be masked by β-blockers; clonidine, reserpine, guanethidine & sympathomimetics. Increased t_½ w/ possible onset of hypoglycaemic manifestations w/ fluconazole. Reduction in antidiuretic activity of desmopressin. Hypoglycaemic effect may be reduced w/ colesevelam. Metformin HCl: Increased C_max & AUC w/ furosemide; nifedipine. Concomitant use w/ other cationic drugs (eg, amiloride, digoxin, morphine, procainamide, quinidine, quinine, ranitidine, triamterene, trimethoprim or vancomycin); iodinated contrast agents. May increase risk of lactic acidosis w/ alcohol; NSAIDs including cyclo-oxygenase II inhibitors, ACE inhibitors, AIIA, diuretics (especially loop diuretics). May reduce efficacy w/ organic cation transporters (OCT) 1 inhibitor (eg, verapamil). May increase GI absorption & efficacy w/ OCT1 inducers (eg, rifampicin). May decrease renal elimination w/ OCT2 inhibitors (eg, cimetidine, dolutegravir, ranolazine, trimethoprim, vandetanib, isavuconazole). May alter efficacy & renal elimination w/ OCT1 & OCT2 inhibitors (eg, crizotinib, olaparib).

Antidiabetic Agents

A10BD02 - metformin and sulfonylureas ; Belongs to the class of combinations of oral blood glucose lowering drugs. Used in the treatment of diabetes.

POM