Index of drugs

The drug is indicated as a therapy added to the diet and exercise to improve glycemic control in adult patients (≥ 18 years old) with type 2 diabetes, in whom the use of the largest tolerated doses of Metformin as monotherapy did not provide adequate glycemic control or who previously used saxagliptin and metformin in combination in separate tablets. The drug is also indicated for use in combination with insulin (eg in 3-drug combination therapy) as a therapy added to the diet and exercise to improve glycemic control in adult patients (≥ 18 years old) with type 2 diabetes mellitus, in whom Insulin and metformin alone do not provide adequate glycemic control. The drug is also indicated for use in combination with a sulphonylurea (ie in a 3-drug combination therapy) as a therapy added to the diet and exercise to improve glycemic control in adult patients) ≥ 18 years old) with type 2 diabetes, the use of maximum tolerated doses, both metformin and a sulphonylurea, does not provide adequate glycemic control.

1 tabl contains 2.5 mg of saxagliptin (as hydrochloride) and 850 mg or 1000 mg of metformin hydrochloride.

The product contains two active substances that reduce blood Glucose with complementary mechanisms of action: saxagliptin - a dipeptidyl peptidase 4 (DPP-4) inhibitor and metformin hydrochloride - a biguanide derivative. Saxagliptin after oral fasting is rapidly absorbed, and the maximum concentration of the drug and the main metabolite is achieved within 2 hrs and 4 h respectively. Inhibition of DPP-4 receptor activity in serum for 24 h results from potency, high affinity and prolonged binding to the active site of the receptor. Binding to proteins of saxagliptin and its major metabolite in blood serum is negligible. Biotransformation takes place primarily with the participation of CYP3A4 / 5. The major metabolite is also a selective, reversible, competitive DPP-4 inhibitor that has half the power of saxagliptin. The average final T_0,5 in the plasma of saxagliptin and its main metabolite is 2.5 h and 3.1 h, respectively, and the average time T_0,5 DPP-4 receptor inhibition is 26.9 h. Saxagliptin is excreted via the kidneys and liver. 75% of the dose is excreted in the urine, 24% as saxagliptin and 36% as its metabolite; 22% are excreted in faeces. Following oral administration of Metformin, peak plasma concentrations occur after 2.5 hours. The absolute bioavailability after administration of tablets containing 500 mg metformin in healthy subjects is approximately 50-60%; approximately 20-30% of the un-absorbed fraction of metformin is excreted in the faeces. Absorption of metformin after oral administration is saturated and incomplete. Steady state in plasma is reached within 24-48 h after administration. The binding to plasma proteins is insignificant. Metformin penetrates into erythrocytes. It is excreted in the urine in unchanged form. Metformin metabolites have not been identified in humans. The drug is excreted by glomerular filtration and tubular secretion. After oral administration of T_0,5 in the elimination phase, it is about 6.5 hours.

Hypersensitivity to the active substances or to any of the excipients or severe hypersensitivity reactions including anaphylactic reactions, anaphylactic shock, angioneurotic edema due to use of the dipeptidyl peptidase 4 (DPP4) inhibitor. Diabetic ketoacidosis, pre-comedic condition in diabetes. Moderate to severe renal insufficiency (creatinine clearance <60 ml / min). acute conditions that may interfere with kidney function such as dehydration, severe infections, shock. Acute and chronic diseases that may cause tissue hypoxia, such as heart or respiratory failure, a recent myocardial infarction, shock. Hepatic dysfunction. Acute alcohol poisoning, alcoholism. Breast-feeding.

It should not be used in patients with type 1 diabetes mellitus or in the treatment of diabetic ketoacidosis. In patients requiring insulin treatment, the preparation can not be used instead of insulin.If pancreatitis is suspected, the preparation and other potentially dangerous drugs should be discontinued. Accumulation of metformin may lead to lactic acidosis (cases of lactic acidosis have been reported in patients with significant renal impairment); other risk factors should be monitored: poorly controlled glycemia, ketoacidosis, prolonged fasting, excessive alcohol intake, hepatic failure and hypoxia. If metabolic acidosis is suspected, the drug should be discontinued and treatment should be started immediately in the hospital. During treatment, serum creatinine should be regularly measured: at least once a year in patients with normal renal function; at least 2-4 times a year in patients with serum creatinine levels that are close to or above the upper limit of normal and in the elderly. Particular caution should be exercised in cases where renal function may be impaired, for example if you start taking medicines to lower your blood pressure, diuretics or NSAIDs. The preparation should be discontinued 48 h before planned surgery under general, spinal or epidural anesthesia. Resumption of therapy should take place not earlier than after 48 hours after the procedure and only after prior assessment of renal function and confirmation that it is correct. In radiological studies, the use of iodinated intravascular contrast agents in patients using metformin may lead to kidney failure accompanied by lactic acidosis - the use of the preparation must be discontinued prior to testing and resumed not earlier than 48 hours after the test and after ensuring that kidney function is normal. As one of the elements of routine control of patients with diabetes, it is recommended to monitor skin disorders such as bullous lesions, ulcers or rashes. If a hypersensitivity reaction to saxagliptin is suspected, the preparation should be discontinued, other potential causes excluded, and alternative treatment for diabetes should be included. Patients with type 2 diabetes mellitus, a well-controlled preparation in whom laboratory abnormalities have occurred and clinical manifestations of the disease (particularly unclear and poorly defined conditions) should be immediately investigated for ketoacidosis or lactate acidosis. The assessment of the patient's condition should refer to the concentration of electrolytes and ketones in the serum, blood Glucose, and if indicated, the pH, lactate, pyruvate and metformin levels in the blood. If any form of acidosis occurs, immediately discontinue use and take appropriate treatment. Experience in the use of saxagliptin in patients over 75 years of age is very limited - caution should be used to treat this group of patients. The efficacy and safety profile of saxagliptin in patients with immune disorders such as organ transplants and in patients with human immunodeficiency syndrome has not been established. The use of CYP3A4 inducers (eg carbamazepine, Dexamethasone, phenobarbital, phenytoin and rifampicin) may reduce the hypoglycaemic effects of saxagliptin. Due to the risk of hypoglycaemia when using insulin or a sulphonylurea in combination with a preparation, a lower dose of insulin or a sulphonylurea may be necessary. The safety and efficacy of the preparation in children under 18 years have not been established.

The preparation should not be used during pregnancy. If you want to become pregnant or if you become pregnant while taking the medicine, stop using it and change to treatment with insulin as soon as possible. It should not be used in women who are breastfeeding.

No clinical trials have been conducted with regard to treatment with the preparation, however, the bioequivalence of the formulation with saxagliptin and metformin used in the combination has been demonstrated.saxagliptin. Treatment with saxagliptin and metformin (for the use of saxagliptin after its addition to previous metformin therapy and initiating treatment with saxagliptin in combination with metformin): Common: upper respiratory tract infections, urinary tract infections, gastrointestinal mucosal infections, nasal sinus infection, nasal infections and throat (only during initial, associated treatment), headache, vomiting.Additional side effects reported with saxagliptin on post-marketing use: common: nausea, rash; uncommon: pancreatitis, hypersensitivity reactions, dermatitis, pruritis, urticaria; rarely: anaphylactic reactions (including anaphylactic shock), angioneurotic edema. Adverse events assessed as at least possibly related to the medicine and reported in at least 2 patients in the saxagliptin 5 mg group compared to the control group. Monotherapy: often: dizziness and fatigue. In combination with metformin: often: dyspepsia and muscle pain. Starting treatment in combination with metformin: common: gastritis, uncommon: joint pain, muscle pain and erectile dysfunction. In combination with metformin and sulphonylureas: common: dizziness, fatigue, bloating. After adding saxagliptin to metformin and a sulphonylurea, the overall incidence of reported hypoglycaemia was 10.2% for saxagliptin 5 mg and 6.3% for placebo. A slight reduction in the absolute number of lymphocytes was observed, which was not associated with clinically significant adverse reactions.metformin. Very common: gastrointestinal symptoms (nausea, vomiting, diarrhea, abdominal pain and decreased appetite, more often at the beginning of treatment, in most cases disappear spontaneously). Common: a metallic aftertaste in your mouth. Very rare: lactic acidosis, vitamin B deficiency₁₂ (Long-term use of metformin was associated with a decrease in the absorption of vitamin B₁₂, which very rarely results in clinically significant deficiency, e.g. megaloblastic anemia), liver dysfunction, hepatitis, urticaria, erythema, pruritus.

Orally. Adults.Patients with glycemia inadequately controlled with the highest tolerated doses of metformin monotherapy: the product should be used at a dose equivalent to the total daily dose of 5 mg saxagliptin given at 2.5 mg twice daily, as well as the dose of metformin previously used.Patients previously taking saxagliptin and metformin tablets separately: take the medicine in the doses corresponding to the previously used.Patients with glycemic inadequately controlled 2-drug combination therapy - insulin and metformin, or patients with glycaemia controlled with 3-drug combination therapy - insulin, metformin and saxagliptin, taken in separate tablets: the dose of the preparation should provide 2.5 mg of saxagliptin twice daily and a dose of metformin similar to the current dose. If the preparation is used in combination with insulin, it may be necessary to reduce the dose of insulin to reduce the risk of hypoglycaemia.Patients with glycemia with inadequately controlled 2-drug combination therapy - a sulphonylurea and metformin, or patients changing 3-drug combination therapy - saxagliptin, metformin and a sulphonylurea, taken on separate tablets: the dose of the preparation should provide 2.5 mg of saxagliptin twice daily and a dose of metformin similar to the current dose. If the preparation is used in combination with a sulphonylurea, a lower dose of a sulphonylurea may be necessary to reduce the risk of hypoglycaemia.Special groups of patients. No dose adjustment is recommended in patients with mild renal impairment. Do not use in patients with moderate or severe renal impairment and in patients with impaired hepatic function.Way of giving. The drug used twice a day during meals.