Janumet XR Dosage/Direction for Use

Recommended dose: General: The dosage of antihyperglycemic therapy with JANUMET 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.
JANUMET XR should be given once daily with a meal preferably in the evening. The dose should be escalated gradually to reduce the gastrointestinal (GI) side effects due to metformin. Additionally, administration of JANUMET XR with food enhances plasma concentrations of metformin. To preserve the modified-release properties, the tablets must not be split, broken, crushed, or chewed before swallowing.
There have been reports of incompletely dissolved JANUMET 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 healthcare provider should assess adequacy of glycemic control.
Dosing Recommendations: The starting dose of JANUMET XR should be based on the patient's current regimen.
JANUMET XR should be given once daily with a meal preferably in the evening. JANUMET XR tablets are available in the following strengths: 50 mg sitagliptin/1000 mg extended-release metformin hydrochloride; 100 mg sitagliptin/1000 mg extended-release metformin hydrochloride.
For patients using the 50 mg sitagliptin/1000 mg metformin hydrochloride extended-release tablet, two tablets should be taken together once daily. The 100 mg sitagliptin/1000 mg metformin hydrochloride extended-release tablet should be taken as a single tablet once daily.
As initial therapy: For patients with type 2 diabetes mellitus, whose hyperglycemia is inadequately controlled with diet and exercise alone, the recommended total daily starting dose of JANUMET XR is 100 mg sitagliptin and 1000 mg metformin hydrochloride. Patients with inadequate glycemic control on this dose can be titrated gradually to reduce gastrointestinal side effects associated with metformin, up to the maximum recommended daily metformin dose of 2000 mg.
For patients inadequately controlled on metformin monotherapy: For patients inadequately controlled on metformin alone, the recommended total daily starting dose of JANUMET XR is 100 mg sitagliptin and the previously prescribed dose of metformin.
For patients inadequately controlled on sitagliptin monotherapy: For patients inadequately controlled on sitagliptin alone, the recommended starting dose of JANUMET XR is 100 mg sitagliptin and 1000 mg metformin hydrochloride. The metformin dose can be titrated as needed to achieve glycemic control. Gradual dose escalation to reduce the gastrointestinal (GI) side effects associated with metformin should be considered. Patients taking sitagliptin monotherapy dose-adjusted for renal impairment should not be switched to JANUMET XR (see CONTRAINDICATIONS).
For patients switching from coadministration of sitagliptin and metformin: For patients switching from coadministration of sitagliptin and metformin, JANUMET XR may be initiated at the previously prescribed dose of sitagliptin and metformin.
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 XR should provide 100 mg total daily dose of sitagliptin. 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 XR should provide 100 mg total daily dose of sitagliptin. 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 XR should provide 100 mg total daily dose of sitagliptin. 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 XR in patients previously treated with other oral antihyperglycemic agents and switched to JANUMET XR. 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 XR and periodically thereafter.
JANUMET XR is contraindicated in patients with an estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m². Discontinue JANUMET XR if the patient's eGFR later falls below 30 mL/min/1.73 m² (see CONTRAINDICATIONS and PRECAUTIONS).
JANUMET XR: Initiation of JANUMET XR in patients with an eGFR ≥ 30 mL/min/1.73 m² and < 45 mL/min/1.73 m² is not recommended. In patients taking JANUMET XR whose eGFR later falls below 45 mL/min/1.73 m2, assess the benefit and risk of continuing therapy and limit dose of the sitagliptin component to 50 mg once day.
Discontinuation for iodinated contrast imaging procedures: Discontinue JANUMET XR 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 XR 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 XR) was compared to the addition of placebo to metformin XR.
While superiority of HbA_1c reduction was demonstrated for JANUMET XR over metformin at Week 20 in the pooled analysis of these two studies, results from the individual studies were inconsistent. Furthermore, efficacy for JANUMET XR over metformin was not observed at Week 54. Therefore, these results do not support use of JANUMET XR 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 XR has not been studied in pediatric patients under 10 years of age.
Use in the elderly: JANUMET XR: Because sitagliptin and metformin are substantially excreted by the kidney and because aging can be associated with reduced renal function, JANUMET XR 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 JANUMET XR: 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.