DOSAGE AND ADMINISTRATION
General Considerations
Dosage of GLUCOVANCE 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. GLUCOVANCE
should be given with meals and should be initiated at a low dose, with gradual
dose escalation as described below, in order to avoid hypoglycemia (largely
due to glyburide), reduce GI side effects (largely due to metformin), and
permit determination of the minimum effective dose for adequate control of
blood glucose for the individual patient.
With initial
treatment and during dose titration, appropriate blood glucose monitoring
should be used to determine the therapeutic response to GLUCOVANCE and to
identify the minimum effective dose for the patient. Thereafter, HbA1c 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 HbA1c to normal or as near normal
as possible. Ideally, the response to therapy should be evaluated using HbA1c (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 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.
GLUCOVANCE in Patients with Inadequate Glycemic Control on Diet and Exercise
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
is 1.25 mg/250 mg once a day with a meal. As initial therapy in patients with
baseline HbA1c >9% or an FPG >200 mg/dL,
a starting dose of GLUCOVANCE 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 as initial therapy, there
was no experience with total daily doses >10 mg/2000 mg per day. GLUCOVANCE
5 mg/500 mg should not be used as initial
therapy due to an increased risk of hypoglycemia.
GLUCOVANCE Use in Patients with Inadequate Glycemic Control on a Sulfonylurea and/or Metformin
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 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 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, 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 should be titrated as described above to achieve adequate
control of blood glucose.
Addition of Thiazolidinediones to GLUCOVANCE Therapy
For patients not adequately controlled
on GLUCOVANCE, a thiazolidinedione can be added to GLUCOVANCE therapy. When
a thiazolidinedione is added to GLUCOVANCE therapy, the current dose of GLUCOVANCE
can be continued and the thiazolidinedione initiated at its recommended starting
dose. For patients needing additional glycemic control, the dose of the thiazolidinedione
can be increased based on its recommended titration schedule. The increased
glycemic control attainable with GLUCOVANCE plus a thiazolidinedione may increase
the potential for hypoglycemia at any time of day. In patients who develop
hypoglycemia when receiving GLUCOVANCE and a thiazolidinedione, consideration
should be given to reducing the dose of the glyburide component of GLUCOVANCE.
As clinically warranted, adjustment of the dosages of the other components
of the antidiabetic regimen should also be considered.
Specific Patient Populations
GLUCOVANCE is not recommended for use during
pregnancy. The initial and maintenance dosing of GLUCOVANCE should be conservative
in patients with advanced age, due to the potential for decreased renal function
in this population. Any dosage adjustment requires a careful assessment of
renal function. Generally, elderly, debilitated, and malnourished patients
should not be titrated to the maximum dose of GLUCOVANCE to avoid the risk
of hypoglycemia. Monitoring of renal function is necessary to aid in prevention
of metformin-associated lactic acidosis, particularly in the elderly. (See
WARNINGS.)
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