Sulfonylureas lower blood glucose in patients with type 2 diabetes by directly stimulating the acute release of insulin from functioning beta cells of pancreatic islet tissue by an unknown process that involves a sulfonylurea receptor on the beta cell. With chronic sulfonylurea treatment , insulin production is not increased and may return to pretreatment values , but insulin efficacy continues and is thought to involve extrapancreatic mechanisms to increase insulin sensitivity in target tissues, such as liver , muscle , and fat as well as in other cells , such as monocytes and erythrocytes . This can result in a decrease in hepatic glycogenolysis and gluconeogenesis . In addition , glibenclamide produce a mild diuresis effect by enhancement of renal free water clearance .

Sulfonylureas are indicated as adjunctive therapy to diet and exercise in the treatment and control of certain patients with type 2 diabetes , which occurs in individuals who produce or secrete insufficient quantities of endogenous insulin or who have developed resistance to endogenous insulin. It is indicated in other diabetes mellitus associated with certain conditions or syndromes , such as : Endocrine disease , including endocrine overactivity due to Cushing’s syndrome , hyperthyroidism , pheochromocytoma , somatostatinoma , or aldosteronoma ; or endocrine underactivity due to hypoparathyroidism – hypocalcemia , type I isolated growth hormone deficiency , multitropic pituitary deficiency ; Genetic syndromes , including inborn errors of metabolism , such as glycogen – storage disease type I , or insulin – resistant syndromes , such as muscular dystrophies , late onset proximal myopathy , or Huntington’s chorea . Sulfonylureas are not effective in the treatment of type 1 diabetes.

Hypoglycemia , including nocturnal hypoglycemia ; Weight gain ; Erythema multiforme or exfoliative dermatitis ; Anemia ( aplastic or hemolytic) ; Blood dyscrasias , specifically , agranulocytosis , leukopenia , pancytopenia ; Cholestatic jaundice ; Hepatitis ; Hepatic porphyria or porphyria cutanea tarda ; Eosinophilia ; Thrombocytopenia ; Changes in sense of taste ; Dizziness ; Drowsiness ; GI disturbances (constipation , diarrhea , flatulence , heartburn , loss of or increase in appetite , nausea , vomiting , stomach pain) ; Headache ; Polyuria ; Blurred vision and/or changes in accommodation ; Photosensitivity .

Significant acidosis ; Severe burns ; Diabetic coma ; Diabetic ketoacidosis , with or without coma ; Hyperosmolar nonketotic coma ; Major surgery ; Severe trauma ; Any other condition that causes severe blood glucose fluctuations or any other condition in which insulin needs change rapidly ; Hypersensitivity to sulfonylurea antidiabetic agent , sulfonamides , or thiazide – type diuretic or any component of the formulation .

Risk – benefit should be considered when the following medical problems exist: Severe diarrhea , gastroparesis , intestinal obstruction , prolonged vomiting or other conditions causing delayed food absorption ; Hepatic disease ; Hyperglycemia – causing conditions such as adrenal insufficiency (not optimally controlled) , debilitated physical condition , malnutrition and pituitary insufficiency ( not optimally controlled) ; Not optimally controlled hypothyroidism ; Renal function impairment.

A disulfiram – like reaction may occur with any of the sulfonylureas when alcohol is ingested concurrently. The risk of hypoglycemia may be increased or prolonged when moderate or large amounts of alcohol have been consumed concurrently with sulfonylurea antidiabetic agents . Concurrent use with angiotensin – converting inhibitors such as captopril and enalapril may cause enhanced hypoglycemia. Mutual interactions of coumarin – or indandione derivative anticoagulants with sulfonylureas have increased their anticoagulant and hypoglycemic effects . Severe hypoglycemia has been reported shortly after concurrent use of glibenclamide with systemic azole antifungals such as miconazole and fluconazole. Sulfonylureas may prolong the effect of barbiturates and barbiturates may prolong the effects of sulfonylurease ; dosage adjustment of the sulfonylurea or the barbiturate may be necessary .Beta –adrenergic blocking agents , including ophthalmics , if significant absorption occurs , may decrease the hypoglycemic effects of sulfonylureas. Cimetidine and ranitidine can significantly decrease the postprandial rise in blood glucose and increase the hypoglycemic effects of glibenclamide in patient with diabetes . Sulfonylureas may significantly increase the plasma concentration of cyclosporine by reducing its metabolism . Use of glibenclamide with ciprofloxacin has caused hypoglycemia. The metabolism of sulfonylureas may be increased by rifabutin and rifampin ; dosage adjustment may be necessary during and after concurrent treatment. The metabolism of sulfonylureas may be decreased by chloramphenicol ; dosage adjustment may be necessary during and after concurrent use . Highly protein – bound medications such as NSAIDs , clofibrate , probenecid , sulfinpyrazon and sulfonamides by displacement of sulfonylurease from protein binding sites and alterations in their renal excretion , enhance the hypoglycemic effects of sulfonylureas when given concurrently.

Blood glucose ; CBC ; Urine glucose and ketones ; Glycosylated hemoglobin (hemoglobin A_1C)

It is recommended that glibenclamide is taken with meal.

• Usual adult and adolescent dose: Antidiabetic –Initial : Oral , 2.5 to 5 mg once a day with breakfast or the first main meal , with dosage changes being made by no more than 2.5 mg at weekly intervals if needed. Patients more sensitive to hypoglycemia may need 1.25 mg a day.
• Maintenance: Oral , 1.25 to 20 mg a day , of which doses up to 10 mg are usually taken as a single dose with breakfast or the first main meal , while doses over 10 mg are usually divided into two daily doses with meals.
• Usual adult prescribing limits: 20 mg daily.
• Usual pediatric dose: Safety and efficacy have not been established.
• Usual geriatric dose: Initial : Oral , 1.25 to 2.5 mg a day with breakfast , with dosage changes being made by no more than 2.5 mg at weekly intervals if needed.
• Maintenance: as usual adult dose

• Tablet 5 mg

• USP DI, 2004
• Up To Date, Vol. 13.1 (2005)
• Martindale, The Complete Drug Reference, 33 rd edition 2002