ered with breakfast or the first main meal. those patients who may be more sensitive to hypoglycemic drugs should be started at 1.25 mg daily. (see precautions section for patients at increased risk.) failure to follow an appropriate dosage regimen may precipitate hypoglycemia. patients who do not adhere to their prescribed dietary and drug regimen are more prone to exhibit unsatisfactory response to therapy. transfer from other hypoglycemic therapy patients receiving other oral antidiabetic therapy: transfer of patients from other oral antidiabetic regimens to glyburide tablets should be done conservatively and the initial daily dose should be 2.5 to 5 mg. when transferring patients from oral hypoglycemic agents other than chlorpropamide to glyburide tablets, no transition period and no initial or priming dose are necessary. when transferring patients from chlorpropamide, particular care should be exercised during the first two weeks because the prolonged retention of chlorpropamide in the body and subsequent overlapping drug effects may provoke hypoglycemia. patients receiving insulin: some type ii diabetic patients being treated with insulin may respond satisfactorily to glyburide tablets. if the insulin dose is less than 20 units daily, substitution of glyburide tablets 2.5 to 5 mg as a single daily dose may be tried. if the insulin dose is between 20 and 40 units daily, the patient may be placed directly on glyburide tablets 5 mg daily as a single dose. if the insulin dose is more than 40 units daily, a transition period is required for conversion to glyburide tablets. in these patients, insulin dosage is decreased by 50% and glyburide tablets 5 mg daily is started. please refer to titration to maintenance dose for further explanation. patients receiving colesevelam: when colesevelam is coadministered with glyburide, maximum plasma concentration and total exposure to glyburide is reduced. therefore, glyburide tablets should be administered at least 4 hours prior to colesevelam. titration to maintenance dose the usual maintenance dose is in the range of 1.25 to 20 mg daily, which may be given as a single dose or in divided doses (see dosage interval section). dosage increases should be made in increments of no more than 2.5 mg at weekly intervals based upon the patient's blood glucose response. no exact dosage relationship exists between glyburide tablets and the other oral hypoglycemic agents. although patients may be transferred from the maximum dose of other sulfonylureas, the maximum starting dose of 5 mg of glyburide tablets should be observed. a maintenance dose of 5 mg of glyburide tablets provides approximately the same degree of blood glucose control as 250 to 375 mg chlorpropamide, 250 to 375 mg tolazamide, 500 to 750 mg acetohexamide, or 1000 to 1500 mg tolbutamide. when transferring patients receiving more than 40 units of insulin daily, they may be started on a daily dose of glyburide tablets 5 mg concomitantly with a 50% reduction in insulin dose. progressive withdrawal of insulin and increase of glyburide tablets in increments of 1.25 to 2.5 mg every 2 to 10 days is then carried out. during this conversion period when both insulin and glyburide tablets are being used, hypoglycemia may occur. during insulin withdrawal, patients should test their urine for glucose and acetone at least three times daily and report results to their physician. the appearance of persistent acetonuria with glycosuria indicates that the patient is a type i diabetic who requires insulin therapy. concomitant glyburide and metformin therapy glyburide tablets should be added gradually to the dosing regimen of patients who have not responded to the maximum dose of metformin monotherapy after four weeks (see usual starting dose and titration to maintenance dose ). refer to metformin package insert. with concomitant glyburide and metformin therapy, the desired control of blood glucose may be obtained by adjusting the dose of each drug. however, attempts should be made to identify the optimal dose of each drug needed to achieve this goal. with concomitant glyburide and metformin therapy, the risk of hypoglycemia associated with sulfonylurea therapy continues and may be increased. appropriate precautions should be taken (see precautions section). maximum dose daily doses of more than 20 mg are not recommended. dosage interval once-a-day therapy is usually satisfactory. some patients, particularly those receiving more than 10 mg daily, may have a more satisfactory response with twice-a-day dosage. specific patient populations glyburide tablets is not recommended for use in pregnancy or for use in pediatric patients. in elderly patients, debilitated or malnourished patients, and patients with impaired renal or hepatic function, the initial and maintenance dosing should be conservative to avoid hypoglycemic reactions. (see precautions section.)

ith sulfonylureas. hematologic reactions: leukopenia, agranulocytosis, thrombocytopenia, hemolytic anemia (see precautions ), aplastic anemia, and pancytopenia have been reported with sulfonylureas. metabolic reactions: hepatic porphyria and disulfiram-like reactions have been reported with sulfonylureas; however, hepatic porphyria has not been reported with glyburide tablets and disulfiram-like reactions have been reported very rarely. cases of hyponatremia have been reported with glyburide and all other sulfonylureas, most often in patients who are on other medications or have medical conditions known to cause hyponatremia or increase release of antidiuretic hormone. the syndrome of inappropriate antidiuretic hormone (siadh) secretion has been reported with certain other sulfonylureas, and it has been suggested that these sulfonylureas may augment the peripheral (antidiuretic) action of adh and/or increase release of adh. other reactions: changes in accommodation and/or blurred vision have been reported with glyburide and other sulfonylureas. these are thought to be related to fluctuation in glucose levels. in addition to dermatologic reactions, allergic reactions such as angioedema, arthralgia, myalgia and vasculitis have been reported. to report suspected adverse reactions, contact avet pharmaceuticals inc. at 1-866-901-drug (3784) or fda at 1-800-fda-1088 or www.fda.gov/medwatch.

atients who have become unresponsive to one or more other sulfonylurea drugs. in addition to its blood glucose lowering actions, glyburide produces a mild diuresis by enhancement of renal free water clearance. disulfiram-like reactions have very rarely been reported in patients treated with glyburide tablets. pharmacokinetics single dose studies with glyburide tablets in normal subjects demonstrate significant absorption of glyburide within one hour, peak drug levels at about four hours, and low but detectable levels at twenty-four hours. mean serum levels of glyburide, as reflected by areas under the serum concentration-time curve, increase in proportion to corresponding increases in dose. multiple dose studies with glyburide tablets in diabetic patients demonstrate drug level concentration-time curves similar to single dose studies, indicating no buildup of drug in tissue depots. the decrease of glyburide in the serum of normal healthy individuals is biphasic; the terminal half-life is about 10 hours. in single dose studies in fasting normal subjects, the degree and duration of blood glucose lowering is proportional to the dose administered and to the area under the drug level concentration-time curve. the blood glucose lowering effect persists for 24 hours following single morning doses in nonfasting diabetic patients. under conditions of repeated administration in diabetic patients, however, there is no reliable correlation between blood drug levels and fasting blood glucose levels. a one year study of diabetic patients treated with glyburide tablets showed no reliable correlation between administered dose and serum drug level. the major metabolite of glyburide is the 4-transhydroxy derivative. a second metabolite, the 3-cishydroxy derivative, also occurs. these metabolites probably contribute no significant hypoglycemic action in humans since they are only weakly active (1/400th and 1/40th as active, respectively, as glyburide) in rabbits. glyburide is excreted as metabolites in the bile and urine, approximately 50% by each route. this dual excretory pathway is qualitatively different from that of other sulfonylureas, which are excreted primarily in the urine. sulfonylurea drugs are extensively bound to serum proteins. displacement from protein binding sites by other drugs may lead to enhanced hypoglycemic action. in vitro , the protein binding exhibited by glyburide is predominantly non-ionic, whereas that of other sulfonylureas (chlorpropamide, tolbutamide, tolazamide) is predominantly ionic. acidic drugs such as phenylbutazone, warfarin, and salicylates displace the ionic-binding sulfonylureas from serum proteins to a far greater extent than the non-ionic binding glyburide. it has not been shown that this difference in protein binding will result in fewer drug-drug interactions with glyburide tablets in clinical use.