Sitaglap M 1000

Generic

Sitagliptin + Metformin Hydrochloride

 

Indications

This is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus when treatment with both sitagliptin and metformin is appropriate. Important limitations of use:

• This should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis, as it would not be efective in these settings.
• This 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 This.

 

Pharmacology

The tablet combines two antihyperglycemic drugs with complementary mechanisms of action to improve blood sugar control in patients with type 2 diabetes. Sitagliptin, a dipeptidyl peptidase-4 (DPP4) inhibitor; and metformin HCl, a member of the biguanide class. Sitagliptin is a dipeptidyl peptidase-4 (DPP4) inhibitor that is believed to work in patients with type 2 diabetes by slowing the inactivation of the incretin hormone. Incretin hormones, including glucagon-like peptide 1 (GLP1) and glucose-dependent insulinotropic polypeptide (GIP), are released from the intestine during the day and their levels rise with meals. These hormones are quickly inactivated by the enzyme DPP4. Secretin is part of the endogenous system involved in the physiological regulation of glucose homeostasis. When blood glucose levels are normal or elevated, GLP1 and GIP increase insulin synthesis and are released from pancreatic β cells through intracellular signaling pathways involving cyclic AMP. GLP1 also reduces the secretion of glucagon from pancreatic alpha cells, which leads to a decrease in glucose production in the liver. By increasing and prolonging active incretin levels, sitagliptin increases insulin release and lowers blood glucose levels in a glucose-dependent manner. The pharmacological mechanism of metformin hydrochloride is different from other types of oral hypoglycemic drugs. Metformin hydrochloride decreases glucose production in the liver, decreases intestinal absorption of glucose, and increases peripheral glucose uptake and utilization.

 

Dosage & Administration

Dose of film-coated tablet: The dosage of this tablet should be individualized on the basis of the patient's current regimen, efectiveness, 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.

This tablet should generally be given twice daily with meals, with gradual dose escalation, to reduce the gastrointestinal (GI) side efects due to metformin.

The starting dose of this tablet should be based on the patient’s current regimen. This tablet should be given twice daily with meals.

The recommended starting dose in patients not currently treated with metformin is 50 mg sitagliptin/500 mg metformin hydrochloride twice daily, with gradual dose escalation recommended to reduce gastrointestinal side efects associated with metformin.

The starting dose in patients already treated with metformin should provide sitagliptin dosed as 50 mg twice daily (100 mg total daily dose) and the dose of metformin already being taken. For patients taking metformin 850 mg twice daily, the recommended starting dose of this tablet is 50 mg sitagliptin/1000 mg metformin hydrochloride twice daily.

No studies have been performed specifcally examining the safety and efcacy of Sitagliptin Phosphate Monohydrate INN/Metformin Hydrochloride BP in patients previously treated with other oral antihyperglycemic agents and switched to Sitagliptin Phosphate Monohydrate INN/Metformin Hydrochloride BP. Any change in therapy of type 2 diabetes should be undertaken with care and appropriate monitoring as changes in glycemic control can occur.

Dose of extended-release tablet: Administer once daily with a meal preferably in the evening. Gradually escalate the dose to reduce the gastrointestinal side effects due to Metformin. May adjust the dosing based on effectiveness and tolerability while not exceeding the maximum recommended daily dose of 100 mg Sitagliptin and 2000 mg Metformin extended-release. Maintain the same total daily dose of Sitagliptin and Metformin when changing between film-coated tablet and extended-release tablet, without exceeding the maximum recommended daily dose of 2000 mg Metformin extended-release.

Patients using two extended-release tablets (such as two 50/500 or two 50/1000 tablets) should take the two tablets together once daily. The 100 mg Sitagliptin/1000 mg Metformin HCI extended-release tablet should be taken as a single tablet once daily.

Patients treated with an insulin secretagogue or insulin: Co-administration of the combination 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.

 

Interaction

Cationic Medications: Cationic drugs are excreted in the tubules of the kidney and should be used with caution.

Phenprocoumon: Metformin may reduce phenprocoumon's anticoagulant impact. As a result, careful monitoring of the INR is advised.

Metformin's hypoglycemia effect can be reduced by taking levothyroxine. Blood glucose levels should be monitored, especially when thyroid hormone therapy is started or stopped, and metformin dosage should be modified if necessary.

 

Contraindications

This tablet is contraindicated in patients with:

• Renal disease or renal dysfunction, e.g., as suggested by serum creatinine levels ≥1.5 mg/dL [males], ≥1.4 mg/dL [females] or abnormal creatinine clearance which may also result from conditions such as cardiovascular collapse (shock), acute myocardial infarction, and septicemia
• Acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma.
• History of a serious hypersensitivity reaction to this tablet or sitagliptin, such as anaphylaxis or angioedema.

This tablet should be temporarily discontinued in patients undergoing radiologic studies involving intravascular administration of iodinated contrast materials, because use of such products may result in acute alteration of renal function.

 

Side Effects

≥5% The most common adverse reactions reported by patients who started using sitagliptin and metformin at the same time were diarrhea, upper respiratory tract infection, and headache, which were more common than those who received placebo.

In patients treated with sitagliptin combined with sulfonylureas and metformin, ≥5% and more common adverse reactions reported in patients treated with placebo combined with sulfonylureas and metformin were hypoglycemia and headache.

Hypoglycemia is the only adverse reaction ≥ 5% reported in patients receiving sitagliptin combined with insulin and metformin, and the incidence is higher than that of patients receiving placebo combined with insulin and metformin.

Nasopharyngitis is the only reported adverse reaction rate ≥ 5% in patients receiving sitagliptin monotherapy and is more frequent than in patients receiving placebo.

The most common (>5%) side effects of starting metformin treatment are diarrhea, nausea/vomiting, loss of appetite, abdominal discomfort, indigestion, fatigue, and headache.

 

Pregnancy & Lactation

Pregnancy Classification B. Because no appropriate and well-controlled trials with Sitagliptin Phosphate Monohydrate INN/Metformin Hydrochloride BP or its individual components have been conducted in

pregnant women, the safety of Sitagliptin Phosphate Monohydrate INN/Metformin Hydrochloride BP in pregnant women is unknown. This tablet should only be taken during pregnancy if absolutely necessary.

Sitagliptin is not known to be excreted in human milk. Because many medications are excreted in human milk, this tablet should be used with caution if given to a nursing mother.

 

Precautions & Warnings

Lactic Acidosis-

• Lactic acidosis can occur due to metformin accumulation. The risk increases with conditions such as sepsis, dehydration, excess alcohol intake, hepatic insufciency, renal impairment, and acute congestive heart failure.
• Symptoms include malaise, myalgias, respiratory distress, increasing somnolence, and nonspecifc abdominal distress. Laboratory abnormalities include low pH, increased anion gap and elevated blood lactate.
• If acidosis is suspected, discontinue this tablet and hospitalize the patient immediately.
• Regular monitoring of thyroid-stimulating hormone (TSH) levels is recommended in patients with hypothyroidism.
• Long-term treatment with metformin has been associated with a decrease in vitamin B12 serum levels which may cause peripheral neuropathy. Monitoring of the vitamin B12 level is recommended.

Others-

• Do not use this tablet in patients with hepatic disease.
• There have been postmarketing reports of acute renal failure, sometimes requiring dialysis. Before initiating this tablet and at least annually thereafter, assess renal function and verify as normal.
• There have been postmarketing reports of acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis. If pancreatitis is suspected, promptly discontinue this tablet.
• Measure hematologic parameters annually.
• Warn patients against excessive alcohol intake.
• May need to discontinue this tablet and temporarily use insulin during periods of stress and decreased intake of fluids and food as may occur with fever, trauma, infection or surgery.
• Promptly evaluate patients previously controlled on this tablet who develop laboratory abnormalities or clinical illness for evidence of ketoacidosis or lactic acidosis.
• When used with an insulin secretagogue (e.g., sulfonylurea) or with insulin, a lower dose of the insulin secretagogue or insulin may be required to reduce the risk of hypoglycemia.
• There have been postmarketing reports of serious allergic and hypersensitivity reactions in patients treated with sitagliptin (one of the components of this tablet ), such as anaphylaxis, angioedema, and exfoliative skin conditions including Stevens-Johnson syndrome. In such cases, promptly stop this tablet, assess for other potential causes, and institute appropriate monitoring and treatment, and initiate alternative treatment for diabetes.
• There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with Sitagliptin Phosphate Monohydrate INN/Metformin Hydrochloride BP or any other anti-diabetic drug.

 

Therapeutic Class

Combination Oral hypoglycemic preparations

 

Storage Conditions

Store below 25°C in a dry place away from light. Keep the medicines in a safe place, out of the reach of children. Do not use later than the date of expiry. To be dispensed only on the prescription of a registered physician.

 

Pharmaceutical Name

Euro Pharma Ltd.