DOSAGE AND ADMINISTRATION
There is no fixed dosage regimen for the management of diabetes mellitus with GLYSET Tablets or any other pharmacologic agent. Dosage of GLYSET must be individualized on the basis of both effectiveness and tolerance while not exceeding the maximum recommended dosage of 100 mg 3 times daily. GLYSET should be taken three times daily at the start (with the first bite) of each main meal. GLYSET should be started at 25 mg, and the dosage gradually increased as described below, both to reduce gastrointestinal adverse effects and to permit identification of the minimum dose required for adequate glycemic control of the patient.
During treatment initiation and dose titration (see below), one-hour postprandial plasma glucose may be used to determine the therapeutic response to GLYSET and identify the minimum effective dose for the patient. Thereafter, glycosylated hemoglobin should be measured at intervals of approximately three months. The therapeutic goal should be to decrease both postprandial plasma glucose and glycosylated hemoglobin levels to normal or near normal by using the lowest effective dose of GLYSET, either as monotherapy or in combination with a sulfonylurea.
Initial Dosage
The recommended starting dosage of GLYSET is 25 mg, given orally three times daily at the start (with the first bite) of each main meal. However, some patients may benefit by starting at 25 mg once daily to minimize gastrointestinal adverse effects, and gradually increasing the frequency of administration to 3 times daily.
Maintenance Dosage
The usual maintenance dose of GLYSET is 50 mg 3 times daily, although some patients may benefit from increasing the dose to 100 mg 3 times daily. In order to allow adaptation to potential gastrointestinal adverse effects, it is recommended that GLYSET therapy be initiated at a dosage of 25 mg 3 times daily, the lowest effective dosage, and then gradually titrated upward to allow adaptation. After 4 – 8 weeks of the 25 mg 3 times daily regimen, the dosage should be increased to 50 mg 3 times daily for approximately three months, following which a glycosylated hemoglobin level should be measured to assess therapeutic response. If, at that time, the glycosylated hemoglobin level is not satisfactory, the dosage may be further increased to 100 mg 3 times daily, the maximum recommended dosage. Pooled data from controlled studies suggest a dose-response for both HbA1c and one-hour postprandial plasma glucose throughout the recommended dosage range. However, no single study has examined the effect on glycemic control of titrating patients' doses upwards within the same study. If no further reduction in postprandial glucose or glycosylated hemoglobin levels is observed with titration to 100 mg 3 times daily, consideration should be given to lowering the dose. Once an effective and tolerated dosage is established, it should be maintained.
Maximum Dosage
The maximum recommended dosage of GLYSET is 100 mg 3 times daily. In one clinical trial, 200 mg 3 times daily gave additional improved glycemic control but increased the incidence of the gastrointestinal symptoms described above.
Patients Receiving Sulfonylureas
Sulfonylurea agents may cause hypoglycemia. There was no increased incidence of hypoglycemia in patients who took GLYSET in combination with sulfonylurea agents compared to the incidence of hypoglycemia in patients receiving sulfonylureas alone in any clinical trial. However, GLYSET given in combination with a sulfonylurea will cause a further lowering of blood glucose and may increase the risk of hypoglycemia due to the additive effects of the two agents. If hypoglycemia occurs, appropriate adjustments in the dosage of these agents should be made.
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