Index of drugs

Type 2 diabetes mellitus in adult patients (to improve glycemic control).monotherapy: in patients who are inadequately controlled only by diet and exercise, where Metformin is inappropriate due to contraindications or intolerance.Two-component oral therapy: in combination with Metformin, when diet and exercise and the use of metformin alone are not sufficient for adequate glycemic control; in combination with a sulphonylurea, when diet and exercise and the use of only the maximum tolerated dose of a sulphonylurea are not sufficient for adequate glycemic control and when metformin is inappropriate due to contraindications or intolerance; in combination with a peroxisome-activated gamma-receptor (PPARγ) receptor agonist, i.e. a thiazolidinedione, if the use of a PPARγ receptor agonist is indicated and when the use of diet and exercise in combination with the PPARγ agonist monotherapy does not provide adequate glycemic control.Ternary oral therapy: in combination with a sulphonylurea and metformin, when the diet and exercise and the use of these drugs are not sufficient for adequate glycemic control; in combination with the PPARγ agonist and metformin, when the use of a PPARγ receptor agonist is indicated and when the use of diet and exercise in combination with these drugs is not sufficient for adequate glycemic control.Combination therapy with insulin: as a supplementary drug to insulin (with or without metformin), when diet and exercise in combination with a fixed dose of insulin do not provide adequate glycemic control.

1 tabl powl. contains 100 mg sitagliptin as monohydrate phosphate.

An antidiabetic drug, a dipeptidyl peptidase 4 (DPP-4) inhibitor. Improved glycemic control may be the result of mediation in increasing the concentration of active incretin hormones. Incretin hormones, including glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are released in the intestine throughout the day, and their concentration increases in response to food intake. The effect of GLP-1 and GIP depends on Glucose, so that when the blood Glucose level is low, insulin release and GLP-1 inhibition of glucagon secretion are not observed. In both GLP-1 and GIP, the stimulation of insulin release increases with an increase in glucose above normal values. In addition, GLP-1 does not interfere with the normal glucagon response to hypoglycaemia. The activity of GLP-1 and GIP is limited by the DPP-4 enzyme, which causes rapid hydrolysis of incretin hormones to produce inactive products. Sitagliptin prevents the hydrolysis of incretin hormones by DPP-4, thereby increasing the concentration of active forms of GLP-1 and GIP in blood plasma. By increasing the concentration of active incretin hormones, sitagliptin increases insulin release and decreases glucagon concentration in a glucose-dependent manner. In patients with type 2 diabetes mellitus and hyperglycemia, these changes in insulin and glucagon levels lead to a reduction in hemoglobin A1c (HbA_1c) and reduction of fasting and postmeal glucose. Following oral administration of a 100 mg dose to healthy subjects, sitagliptin was rapidly absorbed and plasma concentrations peaked within 1-4 hours after administration. The absolute bioavailability of sitagliptin is approximately 87%. The sitagliptin fraction bound in a reversible manner with plasma proteins is low (38%). Sitagliptin is predominantly (79%) eliminated in the urine unchanged, and the metabolism of the drug is of secondary importance. Approx. 16% of the dose is excreted as metabolites. The main enzyme responsible for the limited metabolism of sitagliptin is CYP3A4 with the participation of CYP2C8. Real final T_0,5 is about 12.4 h. The elimination occurs mainly as a result of renal excretion with active tubular secretion. Sitagliptin is a substrate for the human organic 3 anion transporter (hOAT-3), which can participate in the elimination of sitagliptin by the kidneys.It is also a substrate for p-glycoprotein, which can also mediate the elimination of sitagliptin by the kidneys.

Hypersensitivity to the active substance or to any of the excipients.

Do not use the drug in patients with type 1 diabetes mellitus or in the treatment of diabetic ketoacidosis. The use of DPP-4 inhibitors is associated with the risk of acute pancreatitis. Patients should be informed about the characteristic symptom of acute pancreatitis: persistent, severe abdominal pain. After discontinuation of sitagliptin (with or without supportive care), resolution of pancreatitis has been observed, but very rare cases of necrotic or haemorrhagic pancreatitis and / or death have been reported. If pancreatitis is suspected, the preparation should be discontinued as well as other medicines that may raise doubts. If acute pancreatitis is confirmed, sitagliptin treatment should not be restarted. Caution should be exercised in patients with a history of pancreatitis. Hypoglycaemia was observed when sitagliptin was used in combination with insulin or with a sulphonylurea. Therefore, a lower dose of a sulphonylurea or insulin may be considered to reduce the risk of hypoglycaemia. In patients with moderate and severe renal impairment, as well as in patients with ESRD requiring hemodialysis or peritoneal dialysis, a dose reduction of sitagliptin is recommended to achieve plasma levels similar to those seen in patients with normal function kidney. Before you are given sitagliptin in combination with another diabetes medicine, you should check the conditions of use of this medicine in patients with impaired kidney function. If hypersensitivity reactions are suspected, the drug should be discontinued. Other possible causes of the event should be investigated and an alternative treatment method for diabetes should be used. The safety and efficacy of sitagliptin in children and adolescents under 18 years have not yet been established.

Do not use during pregnancy and breast-feeding.

Monotherapy: common: upper respiratory tract infections, nasopharyngitis, hypoglycaemia, headache, osteoarthritis, limb pain; uncommon: dizziness, constipation; frequency unknown: vomiting. In combination with metformin: common: hypoglycaemia, nausea, bloating, vomiting; uncommon: drowsiness, diarrhea, constipation, upper abdominal pain, decreased blood glucose; frequency unknown: pain in the limbs. In combination with a sulphonylurea: common: hypoglycaemia; frequency unknown: vomiting, pain in the limbs. In combination with a sulphonylurea and mimetformin: very common: hypoglycaemia; often: constipation; frequency unknown: vomiting, pain in the limbs. In combination with a PPARγ agonist: common: hypoglycaemia, flatulence, peripheral edema, reduced blood glucose; frequency unknown: vomiting, pain in the limbs. In combination with the PPARγ agonist and metformin: common: hypoglycaemia, peripheral edema; frequency unknown: vomiting, pain in the limbs. In combination with insulin (with or without metformin): common: hypoglycaemia, headache, influenza; uncommon: constipation, dry mouth; frequency unknown: vomiting, pain in the limbs. In addition, in all of the above situations (monotherapy and all associations) frequency unknown: interstitial lung disease, acute pancreatitis, necrotizing or haemorrhagic pancreatitis with or without lethal effect, angioneurotic edema, rash, urticaria, vasculitis of the skin, exfoliative skin diseases (including Stevens-Johnson syndrome), joint pain, muscle pain, back pain, kidney problems, acute renal failure. In clinical trials, a slight increase in the number of white blood cells was observed (difference in the number of white blood cells amounting to approximately 200 cells / μl compared to placebo, mean baseline white blood cell count was approximately 6,600 cells / μl) due to an increase in the number of neutrophils. This phenomenon has been observed in most studies, but not in all of them. This change in laboratory parameters is not considered to be clinically relevant.

Orally. Adults: 100 mg once a day. When used in combination with metformin and / or the PPARγ receptor agonist, the existing dose of metformin and / or the PPARγ receptor agonist should be maintained and sitagliptin administered concomitantly.When sitagliptin is combined with a sulphonylurea or with insulin, a lower dose of a sulphonylurea or insulin may be considered to reduce the risk of hypoglycaemia. If you miss a dose, take it as soon as you remember. Do not take a double dose on the same day. Before you are given sitagliptin in combination with another diabetes medicine, you should check the conditions of use of this medicine in patients with impaired kidney function. In patients with mild renal impairment (creatinine clearance ≥ 50 ml / min), no dose adjustment of sitagliptin is required; with moderate renal impairment (≥30 to <50 ml / min) the dose of sitagliptin is 50 mg once a day; with severe renal impairment (<30 ml / min) or end-stage renal disease (ESRD) requiring hemodialysis or peritoneal dialysis, the dose of sitagliptin is 25 mg once a day, sitagliptin can be taken regardless of the date of dialysis. Because of the need to adjust the dose depending on renal function, it is recommended that renal function be assessed before and during treatment with sitagliptin. No dose adjustment is necessary in patients with mild to moderate hepatic impairment; no studies have been performed in patients with severe hepatic impairment. Elderly patients do not need to adjust their dose; limited data on safety are available for patients ≥75 years of age (use caution). The tablets can be taken regardless of meals.