SITAGLIPTIN-METFORMIN SANDOZ FILM COATED TABLET 50MG/500MG [SIN17121P]

Product Info

SITAGLIPTIN-METFORMIN SANDOZ FILM COATED TABLET 50MG/500MG

[SIN17121P]

4.1 Therapeutic indications
SITAGLIPTIN-METFORMIN SANDOZ is indicated as initial therapy in adult patients with type 2 diabetes mellitus to improve glycemic control when diet and exercise do not provide adequate glycemic control.

SITAGLIPTIN-METFORMIN SANDOZ is indicated as an adjunct to diet and exercise to improve glycemic control in adult patients with type 2 diabetes mellitus who are not adequately controlled on metformin or sitagliptin alone or in patients already being treated with the combination of sitagliptin and metformin.

SITAGLIPTIN-METFORMIN SANDOZ is also indicated in combination with a sulfonylurea (i.e., triple combination therapy) as an adjunct to diet and exercise in adult patients with type 2 diabetes mellitus inadequately controlled with any two of the three agents: metformin, sitagliptin, or a sulfonylurea.

SITAGLIPTIN-METFORMIN SANDOZ is indicated as add-on to insulin (i.e., triple combination therapy) as an adjunct to diet and exercise to improve glycemic control in patients when insulin and metformin alone do not provide adequate glycemic control.

Important Limitations of Use
SITAGLIPTIN-METFORMIN SANDOZ should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis.

SITAGLIPTIN-METFORMIN SANDOZ has not been studied in patients with a history of pancreatitis. It is unknown whether patients with a history of pancreatitis are at increased risk for the development of pancreatitis while using SITAGLIPTIN-METFORMIN SANDOZ (see section 4.4 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

4.2 Posology and method of administration
Recommended Dosing
The dosage of antihyperglycemic therapy with SITAGLIPTIN-METFORMIN SANDOZ 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. Initial combination therapy or maintenance of combination therapy should be individualized and left to the discretion of the health care provider.

SITAGLIPTIN-METFORMIN SANDOZ should generally be given twice daily with meals, with gradual dose escalation, to reduce the gastrointestinal (GI) side effects due to metformin.

The starting dose of SITAGLIPTIN-METFORMIN SANDOZ should be based on the patient’s current regimen. SITAGLIPTIN-METFORMIN SANDOZ should be given twice daily with meals. The following doses are available:

• 50 mg sitagliptin/500 mg metformin hydrochloride

• 50 mg sitagliptin/850 mg metformin hydrochloride

• 50 mg sitagliptin/1000 mg metformin hydrochloride.

Patients inadequately controlled with diet and exercise alone
If therapy with a combination tablet containing sitagliptin and metformin is considered appropriate for a patient with type 2 diabetes mellitus inadequately controlled with diet and exercise alone, the recommended starting dose is 50 mg sitagliptin/500 mg metformin hydrochloride twice daily. Patients with inadequate glycemic control on this dose can be titrated up to 50 mg sitagliptin/1000 mg metformin hydrochloride twice daily.

Patients inadequately controlled on metformin monotherapy
If therapy with a combination tablet containing sitagliptin and metformin is considered appropriate for a patient inadequately controlled on metformin alone, the recommended starting dose of SITAGLIPTIN-METFORMIN SANDOZ should provide sitagliptin dosed as 50 mg twice daily (100 mg total daily dose) and the dose of metformin already being taken.

Patients inadequately controlled on sitagliptin monotherapy
If therapy with a combination tablet containing sitagliptin and metformin is considered appropriate for a patient inadequately controlled on sitagliptin alone, the recommended starting dose of SITAGLIPTIN-METFORMIN SANDOZ is 50 mg sitagliptin/500 mg metformin hydrochloride twice daily. Patients with inadequate control on this dose can 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 SITAGLIPTIN-METFORMIN SANDOZ (see section 4.3).

Patients switching from co-administration of sitagliptin and metformin
For patients switching from sitagliptin co-administrated with metformin, SITAGLIPTIN-METFORMIN SANDOZ may be initiated at the dose of sitagliptin and metformin already being taken.

Patients inadequately controlled on dual combination therapy with any two of the following antihyperglycemic agents: sitagliptin, metformin or a sulfonylurea
If therapy with a combination tablet containing sitagliptin and metformin is considered appropriate in this setting, the usual starting dose of SITAGLIPTIN-METFORMIN SANDOZ 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 hypoglycemia (see section 4.4 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

For patients inadequately controlled on dual combination therapy with insulin and metformin
The usual starting dose of SITAGLIPTIN-METFORMIN SANDOZ 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 section 4.4 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

No studies have been performed specifically examining the safety and efficacy of SITAGLIPTIN-METFORMIN SANDOZ in patients previously treated with other oral antihyperglycemic agents and switched to SITAGLIPTIN-METFORMIN SANDOZ. 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 SITAGLIPTIN-METFORMIN SANDOZ and periodically thereafter.

SITAGLIPTIN-METFORMIN SANDOZ is contraindicated in patients with an estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m².

SITAGLIPTIN-METFORMIN SANDOZ 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 SITAGLIPTIN-METFORMIN SANDOZ product.

Discontinuation for iodinated contrast imaging procedures
Discontinue SITAGLIPTIN-METFORMIN SANDOZ 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 SITAGLIPTIN-METFORMIN SANDOZ if renal function is acceptable (see section 4.4 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

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 sitagliptin-metformin or sitagliptin-metformin XR) was compared to the addition of placebo to metformin or metformin XR.

The results do not support use of sitagliptin-metformin or sitagliptin-metformin XR in pediatric subjects (10 to 17 years old) with type 2 diabetes (see section 5.1 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

In pediatric patients aged 10 to 17 years with type 2 diabetes, the profile of side effects was comparable to that observed in adults.

Sitagliptin-metformin and sitagliptin-metformin XR have not been studied in pediatric patients under 10 years of age.

Geriatric Use
SITAGLIPTIN-METFORMIN SANDOZ
Because sitagliptin and metformin are substantially excreted by the kidney, and because aging can be associated with reduced renal function, SITAGLIPTIN-METFORMIN SANDOZ 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 sections 4.4 and 5.2 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Sitagliptin
Of the total number of subjects (N=3884) in Phase II and III clinical studies of sitagliptin, 725 patients were 65 years and over, while 61 patients were 75 years and over. No overall differences in safety or effectiveness were observed between subjects 65 years and over and younger subjects. While this and other reported clinical experience have not identified differences in responses between the elderly and younger patients, greater sensitivity of some older individuals cannot be ruled out.

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 young patients.

Method of administration
For oral administration.
SITAGLIPTIN-METFORMIN SANDOZ should be given twice daily with meals to reduce the gastrointestinal (GI) side effects due to metformin.

4.3 Contraindications
SITAGLIPTIN-METFORMIN SANDOZ (sitagliptin and metformin HCl) is contraindicated in patients with:

• Severe renal impairment (eGFR < 30 mL/min/1.73 m²) (see section 4.4 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information)

• Hypersensitivity to metformin hydrochloride

• Acute or chronic metabolic acidosis, including diabetic ketoacidosis. Diabetic ketoacidosis should be treated with insulin

• History of a serious hypersensitivity reaction to SITAGLIPTIN-METFORMIN SANDOZ or sitagliptin (one of the components of SITAGLIPTIN-METFORMIN SANDOZ), such as anaphylaxis or angioedema. [see sections 4.4 and 4.8 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information]