Janumet Dosage/Direction for Use

Recommended dose: General: The dosage of antihyperglycemic therapy with JANUMET 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.
JANUMET should generally be given twice daily with meals, with gradual dose escalation, to reduce the gastrointestinal (GI) side effects associated with metformin.
Dosing Recommendations: The starting dose of JANUMET should be based on the patient's current regimen.
JANUMET should be given twice daily with meals. The following doses are available: 50 mg sitagliptin/500 mg metformin hydrochloride; 50 mg sitagliptin/1000 mg metformin hydrochloride.
As initial therapy: For patients with type 2 diabetes mellitus, whose hyperglycemia is inadequately controlled with diet and exercise alone, the recommended starting dose of JANUMET is 50 mg sitagliptin/500 mg metformin hydrochloride twice daily. Patients may be titrated up to 50 mg sitagliptin/1000 mg metformin hydrochloride twice daily.
For patients inadequately controlled on metformin monotherapy: For patients inadequately controlled on metformin alone, the usual starting dose of JANUMET should provide sitagliptin dosed as 50 mg twice daily (100 mg total daily dose) plus the dose of metformin already being taken.
For patients inadequately controlled on sitagliptin monotherapy: For patients inadequately controlled on sitagliptin alone, the usual starting dose of JANUMET is 50 mg sitagliptin/500 mg metformin hydrochloride twice daily. Patients may be titrated up to 50 mg sitagliptin/1000 mg metformin hydrochloride twice daily. Patients taking sitagliptin monotherapy dose-adjusted for renal impairment should not be switched to JANUMET (see CONTRAINDICATIONS).
For patients switching from coadministration of sitagliptin and metformin: For patients switching from coadministration of sitagliptin and metformin, JANUMET may be initiated at the dose of sitagliptin and metformin already being taken.
For patients inadequately controlled on dual combination therapy with any two of the following three antihyperglycemic agents: sitagliptin, metformin or a sulfonylurea: The usual starting dose of JANUMET should provide sitagliptin dosed as 50 mg twice daily (100 mg total daily dose). In determining the starting dose of the metformin component, the patient's level of glycemic control and current dose (if any) of metformin should be considered. Gradual dose escalation to reduce the gastrointestinal (GI) side effects associated with metformin should be considered. Patients currently on or initiating a sulfonylurea may require lower sulfonylurea doses to reduce the risk of sulfonylurea-induced hypoglycemia (see PRECAUTIONS).
For patients inadequately controlled on dual combination therapy with any two of the following three antihyperglycemic agents: sitagliptin, metformin or a PPARγ agonist (i.e. thiazolidinediones): The usual starting dose of JANUMET should provide sitagliptin dosed as 50 mg twice daily (100 mg total daily dose). In determining the starting dose of the metformin component, the patient's level of glycemic control and current dose (if any) of metformin should be considered. Gradual dose escalation to reduce the gastrointestinal (GI) side effects associated with metformin should be considered.
For patients inadequately controlled on dual combination therapy with any two of the following three antihyperglycemic agents: sitagliptin, metformin or insulin: The usual starting dose of JANUMET should provide sitagliptin dosed as 50 mg twice daily (100 mg total daily dose). In determining the starting dose of the metformin component, the patient's level of glycemic control and current dose (if any) of metformin should be considered. Gradual dose escalation to reduce the gastrointestinal (GI) side effects associated with metformin should be considered. Patients currently on or initiating insulin therapy may require lower doses of insulin to reduce the risk of hypoglycemia (see PRECAUTIONS).
No studies have been performed specifically examining the safety and efficacy of JANUMET in patients previously treated with other oral antihyperglycemic agents and switched to JANUMET. Any change in therapy of type 2 diabetes should be undertaken with care and appropriate monitoring as changes in glycemic control can occur.
Recommendations for use in renal impairment: Assess renal function prior to initiation of JANUMET and periodically thereafter.
JANUMET is contraindicated in patients with an estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m² (see CONTRAINDICATIONS and PRECAUTIONS).
JANUMET: JANUMET is not recommended in patients with an eGFR ≥30 mL/min/1.73 m² and < 45 mL/min/1.73 m² because these patients require a lower dosage of sitagliptin than what is available in the fixed combination JANUMET product.
Discontinuation for iodinated contrast imaging procedures: Discontinue JANUMET at the time of, or prior to, an iodinated contrast imaging procedure in patients with an eGFR ≥30 to < 60 mL/min/1.73 m²; in patients with a history of liver disease, alcoholism or heart failure; or in patients who will be administered intra-arterial iodinated contrast. Re-evaluate eGFR 48 hours after the imaging procedure; restart JANUMET if renal function is acceptable (see PRECAUTIONS).
Pediatric Use: The safety and efficacy of the addition of sitagliptin in pediatric patients aged 10 to 17 years with type 2 diabetes and inadequate glycemic control on metformin with or without insulin was assessed in two studies over 54 weeks. The addition of sitagliptin (administered as JANUMET) was compared to the addition of placebo to metformin.
While superiority of HbA_1c reduction was demonstrated for JANUMET over metformin at Week 20 in the pooled analysis of these two studies, results from the individual studies were inconsistent. Furthermore, efficacy for JANUMET over metformin was not observed at Week 54. Therefore, these results do not support use of JANUMET in pediatric subjects (10 to 17 years old) with type 2 diabetes.
In pediatric patients aged 10 to 17 years with type 2 diabetes, the profile of side effects was comparable to that observed in adults.
JANUMET has not been studied in pediatric patients under 10 years of age.
Use in the elderly: JANUMET: Because sitagliptin and metformin are substantially excreted by the kidney and because aging can be associated with reduced renal function, JANUMET 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 (see Monitoring of renal function under PRECAUTIONS).
Sitagliptin phosphate: In clinical studies, the safety and effectiveness of sitagliptin in the elderly (≥65 years,) were comparable to those seen in younger patients (<65 years).
Metformin hydrochloride: Controlled clinical studies of metformin did not include sufficient numbers of elderly patients to determine whether they respond differently from younger patients, although other reported clinical experience has not identified differences in responses between the elderly and younger patients.
Mode of Administration: For oral use.