Glucovance Information
Glucovance (Glyburide; metformin hydrochloride)
Glucovance (Glyburide; metformin hydrochloride) Description
Glucovance (Glyburide; metformin hydrochloride) (Glyburide
and Metformin HCl) Tablets contain 2 oral antihyperglycemic drugs used in
the management of type 2 diabetes, glyburide and metformin hydrochloride.
Glucovance (Glyburide; metformin hydrochloride) Indications And Usage
Glucovance (Glyburide; metformin hydrochloride) (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; metformin hydrochloride) Contraindications
Glucovance (Glyburide; metformin hydrochloride) is contraindicated in patients
with:
Glucovance (Glyburide; metformin hydrochloride) 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; metformin hydrochloride) 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; metformin hydrochloride) 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; metformin hydrochloride)
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; metformin hydrochloride) 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; metformin hydrochloride) should only be used in patients with normal
renal function (see , , and ). Because aging is associated with reduced
renal function, Glucovance (Glyburide; metformin hydrochloride) 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; metformin hydrochloride) (see also and ).
Glucovance (Glyburide; metformin hydrochloride) Adverse Reactions
In
double-blind clinical trials involving Glucovance (Glyburide; metformin hydrochloride) as initial therapy or as
second-line therapy, a total of 642 patients received Glucovance (Glyburide; metformin hydrochloride) , 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; metformin hydrochloride) (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; metformin hydrochloride) (n=365), 181 patients received
Glucovance (Glyburide; metformin hydrochloride) with rosiglitazone and 184 received Glucovance (Glyburide; metformin hydrochloride) 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; metformin hydrochloride)
trials, GI symptoms were the most common adverse events with Glucovance (Glyburide; metformin hydrochloride) and
were more frequent at higher dose levels. In controlled trials, <2% of
patients discontinued Glucovance (Glyburide; metformin hydrochloride) therapy due to GI adverse events.
In postmarketing reports cholestatic jaundice and hepatitis may occur rarely which may progress to liver failure; Glucovance (Glyburide; metformin hydrochloride) should be discontinued if this occurs.
Glucovance (Glyburide; metformin hydrochloride) Dosage And Administration
Dosage of Glucovance (Glyburide; metformin hydrochloride) 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; metformin hydrochloride) 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; metformin hydrochloride) 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; metformin hydrochloride)
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; metformin hydrochloride) 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; metformin hydrochloride) 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; metformin hydrochloride) 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; metformin hydrochloride) 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; metformin hydrochloride) , 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; metformin hydrochloride) should be titrated as described above to achieve adequate
control of blood glucose.
Glucovance (Glyburide; metformin hydrochloride) How Supplied
Glucovance (Glyburide; metformin hydrochloride) 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; metformin hydrochloride) 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; metformin hydrochloride) 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; metformin hydrochloride)
Glucovance (Glyburide; metformin hydrochloride)
Glucovance (Glyburide; metformin hydrochloride)
Glucovance (Glyburide; metformin hydrochloride)
