Glucovance Information
Glucovance (Glyburide)
Glucovance (Glyburide) Description
Glucovance (Glyburide) (Glyburide and Metformin HCl) Tablets contain 2 oral antihyperglycemic drugs used in the management of type 2 diabetes, glyburide and metformin hydrochloride.
Glucovance (Glyburide) Indications And Usage
Glucovance (Glyburide) (Glyburide and Metformin HCl) Tablets is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
Glucovance (Glyburide) Contraindications
Glucovance (Glyburide) is contraindicated in patients with:
Glucovance (Glyburide) should be temporarily discontinued in patients undergoing radiologic studies involving intravascular administration of iodinated contrast materials, because use of such products may result in acute alteration of renal function. (See also .)
Glucovance (Glyburide) Warnings
The administration of oral hypoglycemic drugs has been reported to be associated with increased cardiovascular mortality as compared to treatment with diet alone or diet plus insulin. This warning is based on the study conducted by the University Group Diabetes Program (UGDP), a long-term prospective clinical trial designed to evaluate the effectiveness of glucose-lowering drugs in preventing or delaying vascular complications in patients with non-insulin-dependent diabetes. The study involved 823 patients who were randomly assigned to 1 of 4 treatment groups ( 19 (Suppl. 2):747-830, 1970).
UGDP reported that patients treated for 5 to 8 years with diet plus a fixed dose of tolbutamide (1.5 g per day) had a rate of cardiovascular mortality approximately 2½ times that of patients treated with diet alone. A significant increase in total mortality was not observed, but the use of tolbutamide was discontinued based on the increase in cardiovascular mortality, thus limiting the opportunity for the study to show an increase in overall mortality. Despite controversy regarding the interpretation of these results, the findings of the UGDP study provide an adequate basis for this warning. The patient should be informed of the potential risks and benefits of glyburide and of alternative modes of therapy.
Although only 1 drug in the sulfonylurea class (tolbutamide) was included in this study, it is prudent from a safety standpoint to consider that this warning may also apply to other hypoglycemic drugs in this class, in view of their close similarities in mode of action and chemical structure.
Glucovance (Glyburide) Precautions
Periodic fasting blood glucose (FBG) and HbA measurements should be performed to monitor therapeutic response.
Initial and periodic monitoring of hematologic parameters (eg, hemoglobin/hematocrit and red blood cell indices) and renal function (serum creatinine) should be performed, at least on an annual basis. While megaloblastic anemia has rarely been seen with metformin therapy, if this is suspected, vitamin B deficiency should be excluded.
Of the 642 patients who received Glucovance (Glyburide) in double-blind clinical studies, 23.8% were 65 and older while 2.8% were 75 and older. Of the 1302 patients who received Glucovance (Glyburide) in open-label clinical studies, 20.7% were 65 and older while 2.5% were 75 and older. No overall differences in effectiveness or safety were observed between these patients and younger patients, and other reported clinical experience has not identified differences in response between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
Metformin hydrochloride is known to be substantially excreted by the kidney and because the risk of serious adverse reactions to the drug is greater in patients with impaired renal function, Glucovance (Glyburide) should only be used in patients with normal renal function (see , , and ). Because aging is associated with reduced renal function, Glucovance (Glyburide) should be used with caution as age increases. Care should be taken in dose selection and should be based on careful and regular monitoring of renal function. Generally, elderly patients should not be titrated to the maximum dose of Glucovance (Glyburide) (see also and ).
Glucovance (Glyburide) Adverse Reactions
In double-blind clinical trials involving Glucovance (Glyburide) as initial therapy or as second-line therapy, a total of 642 patients received Glucovance (Glyburide) , 312 received metformin therapy, 324 received glyburide therapy, and 161 received placebo. The percent of patients reporting events and types of adverse events reported in clinical trials of Glucovance (Glyburide) (all strengths) as initial therapy and second-line therapy are listed in .
In a controlled clinical trial of rosiglitazone versus placebo in patients treated with Glucovance (Glyburide) (n=365), 181 patients received Glucovance (Glyburide) with rosiglitazone and 184 received Glucovance (Glyburide) with placebo.
Edema was reported in 7.7% (14/181) of patients treated with rosiglitazone compared to 2.2% (4/184) of patients treated with placebo. A mean weight gain of 3 kg was observed in rosiglitazone-treated patients.
Disulfiram-like reactions have very rarely been reported in patients treated with glyburide tablets.
The incidence of gastrointestinal (GI) side effects (diarrhea, nausea/vomiting, and abdominal pain) in the initial therapy trial are summarized in . Across all Glucovance (Glyburide) trials, GI symptoms were the most common adverse events with Glucovance (Glyburide) and were more frequent at higher dose levels. In controlled trials,
In postmarketing reports cholestatic jaundice and hepatitis may occur rarely which may progress to liver failure; Glucovance (Glyburide) should be discontinued if this occurs.
Glucovance (Glyburide) Dosage And Administration
Dosage of Glucovance (Glyburide) must be individualized on the basis of both effectiveness and tolerance while not exceeding the maximum recommended daily dose of 20 mg glyburide/2000 mg metformin.
With initial treatment and during dose titration, appropriate blood glucose monitoring should be used to determine the therapeutic response to Glucovance (Glyburide) and to identify the minimum effective dose for the patient. Thereafter, HbA should be measured at intervals of approximately 3 months to assess the effectiveness of therapy. The therapeutic goal in all patients with type 2 diabetes is to decrease FPG, PPG, and HbA to normal or as near normal as possible. Ideally, the response to therapy should be evaluated using HbA (glycosylated hemoglobin), which is a better indicator of long-term glycemic control than FPG alone.
No studies have been performed specifically examining the safety and efficacy of switching to Glucovance (Glyburide) therapy in patients taking concomitant glyburide (or other sulfonylurea) plus metformin. Changes in glycemic control may occur in such patients, with either hyperglycemia or hypoglycemia possible. Any change in therapy of type 2 diabetes should be undertaken with care and appropriate monitoring.
Recommended starting dose: 1.25 mg/250 mg once or twice daily with meals.
For patients with type 2 diabetes whose hyperglycemia cannot be satisfactorily managed with diet and exercise alone, the recommended starting dose of Glucovance (Glyburide) is 1.25 mg/250 mg once a day with a meal. As initial therapy in patients with baseline HbA >9% or an FPG >200 mg/dL, a starting dose of Glucovance (Glyburide) 1.25 mg/250 mg twice daily with the morning and evening meals may be used. Dosage increases should be made in increments of 1.25 mg/250 mg per day every 2 weeks up to the minimum effective dose necessary to achieve adequate control of blood glucose. In clinical trials of Glucovance (Glyburide) as initial therapy, there was no experience with total daily doses >10 mg/2000 mg per day.
Recommended starting dose: 2.5 mg/500 mg or 5 mg/500 mg twice daily with meals.
For patients not adequately controlled on either glyburide (or another sulfonylurea) or metformin alone, the recommended starting dose of Glucovance (Glyburide) is 2.5 mg/500 mg or 5 mg/500 mg twice daily with the morning and evening meals. In order to avoid hypoglycemia, the starting dose of Glucovance (Glyburide) should not exceed the daily doses of glyburide or metformin already being taken. The daily dose should be titrated in increments of no more than 5 mg/500 mg up to the minimum effective dose to achieve adequate control of blood glucose or to a maximum dose of 20 mg/2000 mg per day.
For patients previously treated with combination therapy of glyburide (or another sulfonylurea) plus metformin, if switched to Glucovance (Glyburide) , the starting dose should not exceed the daily dose of glyburide (or equivalent dose of another sulfonylurea) and metformin already being taken. Patients should be monitored closely for signs and symptoms of hypoglycemia following such a switch and the dose of Glucovance (Glyburide) should be titrated as described above to achieve adequate control of blood glucose.
Glucovance (Glyburide) How Supplied
Glucovance (Glyburide) tablet is a pale yellow, capsule-shaped, bevel-edged, biconvex, film-coated tablet with "" debossed on one side and "" debossed on the opposite side.
Glucovance (Glyburide) tablet is a pale orange, capsule-shaped, bevel-edged, biconvex, film-coated tablet with "" debossed on one side and "" debossed on the opposite side.
Glucovance (Glyburide) tablet is a yellow, capsule-shaped, bevel-edged, biconvex, film-coated tablet with "" debossed on one side and "" debossed on the opposite side.
Glucovance (Glyburide)
Glucovance (Glyburide)
Glucovance (Glyburide)
Glucovance (Glyburide)
