Posology : מינונים

2     DOSAGE AND ADMINISTRATION
2.1   Adults with normal renal function (estimated glomerular filtration rate [eGFR] ≥ 90 mL/min/1.73 m2)
The dose of JANUET XR should be individualized on the basis of the patient’s current regimen, effectiveness, and tolerability while not exceeding the maximum recommended daily dose of 100 mg sitagliptin and 2000 mg metformin hydrochloride (HCl). Initial combination therapy or maintenance of combination therapy should be individualized and left to the discretion of the health care provider.
•    In patients not currently treated with metformin, the recommended total daily starting dose of JANUET XR is 100 mg sitagliptin and 1000 mg metformin HCl extended-release. Patients with inadequate glycemic control on this dose of metformin can be titrated gradually, to reduce gastrointestinal side effects associated with metformin, up to the maximum recommended daily dose.
•    In patients already treated with metformin, the recommended total daily starting dose of JANUET XR is 100 mg sitagliptin and the previously prescribed dose of metformin.
•    For patients taking metformin immediate-release 850 mg twice daily or 1000 mg twice daily, the recommended starting dose of JANUET XR is two 50 mg sitagliptin/1000 mg metformin HCl extended-release tablets taken together once daily.
•    Maintain the same total daily dose of sitagliptin and metformin when changing between JANUET (sitagliptin and metformin HCl immediate-release) and JANUET XR. Patients with inadequate glycemic control on this dose of metformin can be titrated gradually, to reduce gastrointestinal side effects associated with metformin, up to the maximum recommended daily dose.
JANUET XR should be administered with food to reduce the gastrointestinal side effects associated with the metformin component. JANUET XR should be given once daily with a meal preferably in the evening. JANUET XR should be swallowed whole. The tablets must not be split, crushed, or chewed before swallowing. There have been reports of incompletely dissolved JANUET XR tablets being eliminated in the feces. It is not known whether this material seen in feces contains active drug. If a patient reports repeatedly seeing tablets in feces, the health care provider should assess adequacy of glycemic control.
The 100 mg sitagliptin/1000 mg metformin HCl extended-release tablet should be taken as a single tablet once daily. Patients using two JANUET XR tablets (such as two 50 mg sitagliptin/500 mg metformin HCl extended-release tablets or two 50 mg sitagliptin/1000 mg metformin HCl extended-release tablets) should take the two tablets together once daily.
Patients treated with an insulin secretagogue or insulin
Coadministration of JANUET XR with an insulin secretagogue (e.g., sulfonylurea) or insulin may require lower doses of the insulin secretagogue or insulin to reduce the risk of hypoglycemia [see Warnings and Precautions (5.9)].
No studies have been performed specifically examining the safety and efficacy of JANUET XR in patients previously treated with other oral antihyperglycemic agents and switched to JANUET XR. Any change in therapy of type 2 diabetes should be undertaken with care and appropriate monitoring as changes in glycemic control can occur.
2.2 Recommendations for Use in Renal Impairment
An eGFR should be assessed before initiation of treatment with metformin-containing products and at least annually thereafter. In patients at an increased risk of further progression of renal impairment and in the elderly, renal function should be assessed more frequently, e.g. every 3-6 months.
Factors that may increase the risk of lactic acidosis [see Warnings and Precautions (5.1)] should be reviewed before considering initiation of metformin in patients with eGFR< 60 mL/min/1.73 m2.
If no adequate strength of JANUET XR is available, individual monocomponents should be used instead of the fixed-dose combination.



eGFR mL/min/1.73           Metformin                                    Sitagliptin m2
60-89                      Maximum daily dose is 2550 mg.               Maximum daily dose is 100 mg.
Dose reduction may be considered in relation to declining renal function.

45-59                      Maximum daily dose is 2000 mg.               Maximum daily dose is 100 mg.
The starting dose is at most half of the maximum dose.

30-44                      Maximum daily dose is 1000 mg.               Maximum daily dose is 50 mg.
The starting dose is at most half of the maximum dose.
< 30                       Metformin is contraindicated.                Maximum daily dose is 25 mg.