nued and proper supportive therapy instituted. In other metformin clinical trials, hypoglycemia has not been seen even with ingestion of up to 85grams of metformin, although lactic acidosis has occurred in such circumstances (seeWARNINGS). Metformin is dialyzable with a clearance of up to 170mL/min under good hemodynamic conditions. Therefore, hemodialysis may be useful for removal of accumulated drug from patients in whom metformin overdosage is suspected.
DOSAGE AND ADMINISTRATION
GLUMETZA should be taken once daily. However, there is no fixed dosage regimen for the management of hyperglycemia in patients with type2 diabetes with GLUMETZA or any other pharmacologic agent. Dosage of GLUMETZA must be individualized on the basis of both effectiveness and tolerance, while not exceeding the maximum recommended daily dose. The maximum recommended daily dose of GLUMETZA is 2000mg. GLUMETZA therapy should generally be initiated with 1000mg daily which should be taken with food preferably in the evening. Gradual dose escalation from this low dose is recommended both to reduce gastrointestinal side effects and to permit identification of the minimum dose required for adequate glycemic control. During treatment initiation and dose titration (seeRecommended Dosing Schedule), fasting plasma glucose should be used to determine the therapeutic response to GLUMETZA and identify the minimum effective dose. Thereafter, glycosylated hemoglobin should be measured at intervals of approximately three months. The therapeutic goal should be to decrease both fasting plasma glucose and glycosylated hemoglobin levels to normal or near normal by using the lowest effective dose of GLUMETZA, either when used as monotherapy or in combination with sulfonylurea or insulin.
Monitoring of blood glucose and glycosylated hemoglobin will also permit detection of primary failure, i.e.,inadequate lowering of blood glucose at the maximum recommended dose of medication, and secondary failure, i.e.,loss of an adequate blood glucose lowering response after an initial period of effectiveness. Short-term administration of GLUMETZA may be sufficient during periods of transient loss of control in patients usually well-controlled on diet alone. GLUMETZA tablets must be swallowed whole and never split, crushed or chewed. Occasionally, the inactive ingredients of GLUMETZA 500mg may be eliminated in the feces as a soft, hydrated mass, while the 1000mg may leave an insoluble shell. (SeePatient Information)
Recommended Dosing Schedule
Adults - In general, clinically significant responses are not seen at doses below 1500mg per day. However, a lower recommended starting dose and gradually increased dosage is advised to minimize gastrointestinal symptoms. The starting dose of GLUMETZA is 1000mg once daily which in order to maximize therapeutic efficacy must be taken with food preferably in the evening. Dosage increases should be made in increments of 500mg weekly, up to a maximum of 2000mg once daily with the evening meal. If glycemic control is not achieved on GLUMETZA 2000mg once daily, a trial of GLUMETZA 1000mg twice daily should be considered. (SeeCLINICAL PHARMACOLOGY, Clinical Studies)
In one trial, patients treated with immediate release metformin were switched to GLUMETZA. Results of this trial suggest that patients receiving immediate release metformin treatment can be switched to GLUMETZA once daily at the same total daily dose, up to 2000mg once daily. Following a s
