Yasitara (Yasitara)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Active substanceSitagliptinSitagliptin
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    • Dosage form: & nbspfilm coated tablets
    Composition:

    Each film-coated tablet contains:

    Active substance:

    Sitagliptin phosphate monohydrate 32,125 mg, 64.25 mg, 128.5 mg in terms of sitagliptin 25 mg, 50 mg, 100 mg

    Excipients:

    Core: calcium hydrophosphate - 30.0 mg / 60.0 mg / 120.0 mg; croscarmellose sodium 2.0 mg / 4.0 mg / 8.0 mg; povidone K90 (kollidone 90F) - 1.875 mg / 3.75 mg / 7.5 mg; cellulose microcrystalline - 30.0 mg / 60.0 mg / 120.0 mg; magnesium stearate 1.0 mg / 2.0 mg / 4.0 mg; sodium stearyl fumarate 3.0 mg / 6.0 mg / 12.0 mg.

    Film Sheath: Polyvinyl alcohol - 1.6 mg / 3.2 mg / 6.4 mg, Macrogol 4000 0.8 mg / 1.6 mg / 3.2 mg, talc 0.65 mg / 1.3 mg / 2.6 mg , titanium dioxide - 0.95 mg / 1.9 mg / 3.8 mg).
    Description:

    Tablets of 25 mg: round biconvex tablets, covered with a film coating of white color. On the cross section, the nucleus is white or almost white in color.

    Tablets of 50 mg: round biconvex tablets with a risk, covered with a film shell of white color. On the cross section, the nucleus is white or almost white in color.
    Tablets of 100 mg: oval biconvex tablets, covered with a film coating of white color. On the cross section, the nucleus is white or almost white in color.
    Pharmacotherapeutic group:Hypoglycemic agent - dipeptidyl peptidase - 4 inhibitor
    ATX: & nbsp

    A.10.B.H   Inhibitors of dipeptidyl peptidase 4 (DPP-4)

    A.10.B.H.01   Sitagliptin

    Pharmacodynamics:

    Sitagliptin is an orally active, highly selective inhibitor of the enzyme dipeptidyl peptidase 4 (DPP-4), intended for the treatment of type 2 diabetes mellitus.

    Sitagliptin differs in chemical structure and pharmacological action from analogues of glucagon-like peptide-1 (GLP-1), insulin, derivatives sulfonylureas, biguanides, gamma receptor agonists, peroxisome proliferator activated (PPAR-γ), inhibitors of alpha-glycosidase, analogs of amylin. Inhibiting DPP-4, sitagliptin increases the concentration of 2 known hormones of the incretin family: GLP-1 and glucose-dependent insulinotropic peptide (HIP). Hormones of the family of incretins are secreted in the intestine within 24 hours, their concentration rises in response to food intake. Incretiny are part of the internal physiological system of regulation of glucose homeostasis. With a normal or elevated blood glucose concentration, the hormones of the incretin family promote an increase in the synthesisinsulin, as well as its secretion (3-cells of the pancreas due to signaling intracellular mechanisms associated with cyclic adenosine monophosphate (AMP).

    GLP-1 also contributes to the suppression of increased secretion of glucagon by the alpha-cells of the pancreas. Reducing the concentration of glucagon on the background of increasing insulin concentration helps to reduce the production of glucose by the liver, which eventually leads to a decrease in glycemia.

    At a low blood glucose concentration, the listed effects of incretins on the release of insulin and the decrease in glucagon secretion are not observed. GLP-1 and HIP do not affect the release of glucagon in response to hypoglycemia. In physiological conditions, the activity of incretins is limited to DPP-4, which rapidly hydrolyses incretins with the formation of inactive products.

    Sitagliptin prevents the incretin hydrolysis by DPP-4. thereby increasing the plasma concentrations of the active forms of GLP-1 and HIP. By increasing the concentration of incretin, sitagliptin increases the glucose-dependent release of insulin and helps to reduce the secretion of glucagon. In patients with type 2 diabetes mellitus with hyperglycemia, these changes in the secretion of insulin and glucagon lead to a decrease in the concentration of glycated hemoglobin (HbA1C) and a decrease in plasma glucose concentration, determined on an empty stomach and after a loading test.

    In patients with type 2 diabetes, taking a single dose of sitagliptin leads to inhibition of the activity of the DPP-4 enzyme within 24 hours, which leads to an increase in the concentration of circulating incretin GLP-1 and HIP in 2-3 times, an increase in the plasma concentration of insulin and C-peptide , a decrease in the concentration of glucagon in the blood plasma, a decrease in fasting glycemia, as well as a decrease in glycemia after a glucose load or food load.

    Studies to assess the cardiovascular safety of sitagliptin (TECOS)

    In a study evaluating the cardiovascular safety of sitagliptin (TECOS) patients took sitagliptin 100 mg per day (or 50 mg per day, if the initial value of the calculated rate of glomerular filtration (eGFR) was ≥30 and <50 mL / min / 1.73 m2), or placebo, which were added to standard therapy in accordance with existing national standards for the determination of target levels HbA1C and control of cardiovascular risk factors. At the end of the average follow-up period of 3 years, in patients with type 2 diabetes, the reception of sitagliptin inthe addition to standard treatment did not increase the risk of serious cardiovascular adverse events (risk ratio 0.98, 95% confidence interval, 0.89-1.08, p <0.001 for evidence of lack of superiority) or risk of hospitalization due to heart failure (risk ratio 1.00, 95% confidence interval 0.83 - 1.20, p = 0.98 for difference in risk frequency), compared with standard treatment without additional sitagliptin.

    Pharmacokinetics:

    The pharmacokinetics of sitagliptin has been studied in healthy individuals and patients with type 2 diabetes mellitus.

    Suction

    After ingestion of the drug in a dose of 100 mg in healthy individuals, rapid absorption of sitagliptin with the achievement of Cmah in 1-4 hours. The area under the curve "concentration-time" (AUC) increases in proportion to the dose and is 8.52 μmol / L * h in healthy volunteers at a dose of 100 mg in healthy volunteers. FROMmah was 950 nmol / l.

    The absolute bioavailability of sitagliptin is approximately 87%. Intra- and interindividual coefficients of variability AUC sitagliptin are insignificant. Simultaneous intake of fatty foods does not affect the pharmacokinetics of sitagliptin, therefore sitagliptin can be administered regardless of food intake.

    Distribution

    Plasma AUC sitagliptin increased by approximately 14% after the next dose of the drug at a dose of 100 mg to achieve the equilibrium after the first dose.

    After a single dose in a dose of 100 mi- average volume of distribution (Vd) Sitagliptin in healthy volunteers was approximately 198 liters. The binding of sitagliptin to plasma proteins is 38%.

    Metabolism

    Metabolized only a small part of the drug received in the body. After the introduction 14C-labeled sitagliptin inside about 16% of the radioactive drug was excreted as its metabolites. Traces of six metabolites of sitagliptin, probably not possessing DPP-4 inhibitory activity, were found. In studies in vitro it was found that the primary enzyme involved in the limited metabolism of sitagliptin. is an CYP3A4 with CYP2C8.

    Excretion

    Approximately 79% of sitagliptin is excreted unchanged in urine.

    Within 1 week after taking the drug, healthy volunteers 14C-labeled sitagliptin was excreted: 87% by the kidneys and 13% by the intestine.

    The half-life (T1 / 2) of sitagliptin for oral administration at a dose of 100 mg is approximately 12.4 hours. The renal clearance is approximately 350 ml / min.The excretion of sitagliptin is carried out primarily by excretion by the kidneys according to the mechanism of active tubular secretion. Sitagliptin is a substrate for a transporter of organic human anions of the third type (hOAT-3), which can be involved in the process of releasing sitagliptin by the kidneys. Clinically Involvement hOAT-3 in transport, sitagliptin has not been studied. Sitagliptin is also a substrate of p-glycoprotein, which can also participate in the process of renal elimination of sitagliptin. but ciclosporin, which is an inhibitor of p-glycoprotein, did not reduce the renal clearance of sitagliptin.

    Pharmacokinetics in special clinical cases

    Patients with renal insufficiency

    An open study of sitagliptin at a dose of 50 mg / day was conducted to study its pharmacokinetics in patients with varying degrees of severity of chronic renal failure. The patients included in the study were divided into groups with mild renal insufficiency (CK 50-80 ml / min), moderate renal failure (CK 30-50 ml / min) and severe renal insufficiency (KC less than 30 ml / min) , as well as patients with terminal stage of chronic renal failure (CRF) who need dialysis.

    In patients with mild renal insufficiency, there was no clinically significant change in the plasma sitagliptin concentration compared to the control group of healthy volunteers.

    Increase AUC Sitagliptin was approximately 2-fold compared with the control group in patients with moderate-level renal failure, approximately 4-fold increase AUC was noted in patients with severe renal insufficiency, as well as in patients with end-stage renal disease, compared with the control group. Sitagliptin was slightly removed from the systemic blood flow by hemodialysis: only 13.5% of the dose was removed from the body during a 3-4 hour dialysis session.

    Thus, in order to achieve a therapeutic drug concentration in the blood plasma (similar to that in patients with normal renal function), patients with moderate and severe renal insufficiency require dose adjustment.

    Patients with hepatic insufficiency

    In patients with moderate hepatic insufficiency (7-9 points on the Child-Pugh scale), the mean AUC and Cmah sitagliptina with a single admission of 100 mg increase by approximately 21% and 13%, respectively. Thus, correction of the dose of the drug for hepatic insufficiency of mild and moderate severity is not required.

    There are no clinical data on the use of sitagliptin in patients with severe hepatic insufficiency (more than 9 on the Child-Pugh scale). However, due to the fact that the drug is primarily excreted by the kidneys, there should not be a significant change in the pharmacokinetics of sitagliptin in patients with severe hepatic insufficiency.

    Elderly patients

    The age of the patients did not have a clinically significant effect on pharmacokinetic parameters of sitagliptin. In comparison with young patients, in elderly patients (65-80 years) the concentration of sitagliptin is approximately 19% higher. Correction of the dose of the drug according to age is not required.

    Indications:

    Monotherapy

    Yasitara is indicated as an adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes mellitus.

    Combination Therapy

    Combination with metformin

    The drug Yasitar in combination with metformin is indicated in patients with type 2 diabetes to improve glycemic control as a starting therapy, or when diet and exercise in combination with monotherapy with one of these drugs do not lead to adequate glycemic control.

    Combination with sulfonylurea derivatives

    The drug Yasitar in combination with derivatives of sulfonylureas is indicated in patients with type 2 diabetes to improve glycemic control when diet and exercise combined with monotherapy with one of these drugs do not lead to adequate glycemic control.

    Combination with agonists PPAR-γ

    Yasitar preparation in combination with agonists PPAR-γ (thiazolidinediones) is indicated in patients with type 2 diabetes to improve glycemic control when diet and exercise combined with monotherapy with one of the listed drugs do not lead to adequate glycemic control.

    Combination with metformin and sulfonylurea derivatives

    The drug Yasitar in combination with metformin and derivatives of sulfonylureas is indicated in patients with type 2 diabetes to improve glycemic control,when diet and exercise in combination with therapy with two of these drugs do not lead to adequate glycemic control.

    Combination with metformin and agonists PPAR-γ

    The drug Yasitar in combination with metformin and agonists PPAR-γ (thiazolidinediones) is indicated in patients with type 2 diabetes mellitus to improve glycemic control when diet and exercise combined with therapy with the two of these drugs do not lead to adequate glycemic control.

    Combination with insulin

    Yasitara is indicated for patients with type 2 diabetes mellitus as an adjunct to insulin (with or without metformin) in cases where diet, exercise and a stable dose of insulin do not lead to adequate glycemic control.

    Contraindications:

    Type 1 diabetes mellitus; diabetic ketoacidosis; pregnancy; the period of breastfeeding; increased sensitivity to sitagliptin or any auxiliary substance of the drug.

    Use in children and adolescents under the age of 18 (due to the lack of data on the efficacy and safety of sitagliptin in this age group).

    Carefully:

    Renal insufficiency

    The main way to remove sitagliptin from the body is renal excretion. To achieve the same plasma concentrations as patients with normal renal excretory function, patients with moderate and severe renal insufficiency and patients with terminal stage of HIN requiring hemodialysis or peritoneal dialysis, correction (reduction) of the dose of sitagliptin (cm See the section "Method of administration and dose: Patients with renal insufficiency").

    Pancreatitis

    See section "Special instructions. Pancreatitis".

    Pregnancy and lactation:

    There were no controlled clinical studies of sitagliptin in pregnant women, therefore, there is no data on the safety of its use during pregnancy. The drug Yasitar, like other oral hypoglycemic drugs, is not recommended for use during pregnancy. There is no data on the penetration of sitagliptin into breast milk. Therefore, the drug Yasitar contraindicated during breastfeeding.

    Dosing and Administration:

    The recommended dose of Yasitara is 100 mg once a day orally as a monotherapy or in combination with metformin, or sulfonylurea derivatives, or agonists PPAR-γ (thiazolidinediones), or insulin (with or without metformin), or in combination with metformin and a sulfonylurea compound, or metformin and agonists PPAR-γ.

    The drug Yasitara can be taken regardless of food intake. The dosage regimen of metformin, sulfonylurea derivatives and agonists PPAR-γ should be selected based on the recommended doses for these drugs.

    When combining Yasitara with sulfonylureas or with insulin, the traditionally recommended dose of a sulfonylurea or insulin derivative is advisable to reduce to reduce the risk of developing sulfonated or insulin-induced hypoglycemia (see Specific guidance, Hypoglycemia).

    If the patient misses the Yasitara drug, the drug should be taken as soon as possible after the patient remembers the missed drug intake.

    It is unacceptable to take a double dose of Yasitara on the same day.

    Patients with renal insufficiency

    Patients with mild renal insufficiency (creatinine clearance (CK) ≥50 ml / min, approximately corresponding to a serum creatinine concentration ≤1.7 mg / dL in males and ≤1.5 mg / dl in females) are not required to adjust the dose of Yasitara .

    For patients with moderate renal insufficiency (CK ≥30 mL / min, but <50 mL / min, approximately equivalent to serum creatinine> 1.7 mg / dL, but ≤3 mg / dl in men and> 1.5 mg / dl, but ≤2.5 mg / dl in women), the dose of Yasitara is 50 mg once daily.

    For patients with severe renal failure (CK <30 mL / min, approximately equivalent to a serum creatinine concentration of> 3 mg / dl in men and> 2.5 mg / dl in women) or with terminal stage of HIN requiring hemodialysis or peritoneal dialysis, the dose of Yasitar is 25 mg once a day. The drug Yasitara can be used regardless of the schedule of the dialysis procedure.

    Due to the need for dose adjustment in patients with renal insufficiency, it is recommended that the kidney function be evaluated before treatment with Yasitar and periodically during the treatment.

    Patients with hepatic insufficiency

    It is not necessary to correct the dose of Yasitara in patients with mild and moderate hepatic insufficiency. The drug was not studied in patients with severe hepatic insufficiency.

    Elderly patients

    It is not required to correct the dose of Yasitara in elderly patients.

    Side effects:

    Sitagliptin is generally well tolerated both in the monotherapy regimen, and in combination with other hypoglycemic drugs. In clinical trials, the overall incidence of undesired events, as well as the frequency of drug withdrawal due to adverse events, were similar to those observed with placebo.

    According to 4 placebo-controlled studies (duration 18-24 weeks) of sitagliptin in a daily dose of 100-200 mg as a monotherapy or combination therapy with metformin or pioglitazone, there were no adverse events associated with the study drug, the frequency of which exceeded 1% in the group of patients who took sitagliptin. The safety profile of the daily dose of 200 mg was comparable to the safety profile of the daily dose of 100 mg.

    Analysis of the data obtained in the above clinical studies showed that the overall incidence of hypoglycemia in patients taking sitagliptin, was similar to that of placebo (sitagliptin 100 mg - 1.2%, sitagliptin 200 mg - 0.9%, placebo - 0.9%). The frequency of monitored adverse events from the gastrointestinalof the tract when receiving sitagliptin in both doses was similar to that of placebo (except for the more frequent occurrence of nausea when taking sitagliptin at a dose of 200 mg per day): abdominal pain (sitagliptin 100 mg - 2.3%, sitagliptin 200 mg - 1.3%, placebo - 2.1%), nausea (1.4%, 2.9%, 0.6%), vomiting (0.8%, 0.7%, 0.9% ), diarrhea (3.0%, 2.6%, 2.3%).

    In all studies, adverse reactions in the form of hypoglycemia were recorded on the basis of all reports of clinically expressed symptoms of hypoglycemia: a parallel measurement of blood glucose concentration was not required.

    Start combination therapy with metformin

    In a 24-week placebo-controlled factorial study of starting combination therapy with sitagliptin in a daily dose of 100 mg and metformin at a daily dose of 1000 mg or 2000 mg (sitagliptin 50 mg + metformin 500 mg or 1000 mg x 2 times a day), the following adverse events were observed in the combination treatment group compared with the metformin monotherapy group: adverse drug reactions observed with a frequency of ≥1% in the sitagliptin treatment group and in the bowl than in the metformin treatment group in monotherapy: diarrhea (sitagliptin + metformin - 3,5%, metformin - 3,3%), dyspepsia (1.3%, 1.1%), headache (1.3%, 1.1%), flatulence (1.3%, 0.5%), hypoglycemia (1 , 1%, 0.5%), vomiting (1.1%, 0.3%).

    Combination with derivatives of sulfonylurea or derivatives of sulfonylureas and metformin

    In a 24-week, placebo-controlled study of sitagliptin combined therapy (daily dose of 100 mg) and glimepiride or glimepiride and metformin in the study drug group compared with the placebo group and glimepiride or glimepiride and metformin, the following undesirable phenomena were observed: adverse drug reactions observed with a frequency of ≥1% in the sitagliptin treatment group and in the bowl than in the combination therapy group with placebo: hypoglycemia (sitagliptin - 9.5%, placebo - 0.9%).

    Start combination therapy with agonists PPAR-γ

    In a 24-week study of starting combination therapy with sitagliptin in a daily dose of 100 mg and pioglitazone at a daily dose of 30 mg, the following adverse events were observed in the combination treatment group compared to monotherapy with pioglitazone: related adverse reactions observed with a frequency of ≥1% in the sitagliptin treatment group and the bowl than in the pioglitazone treatment group in monotherapy: asymptomatic decrease in the concentration of glucose in the blood (sitagliptin + pioglitazone - 1,1%, pioglitazone - 0,0%), symptomatic hypoglycemia (0.4%, 0.8%).

    Combination with agonists PPAR-γ and metformin

    According to a placebo-controlled study in the treatment of sitagliptin (daily dose of 100 mg) in combination with rosiglitazone and metformin in the study drug group, compared with the group of patients taking placebo with rosiglitazone and metformin, the following adverse events were observed:

    At week 18 of observation: adverse drug reactions observed with a frequency of ≥1% in the sitagliptin treatment group and in the bowl than in the combination therapy group with placebo: headache (sitagliptin - 2.4%, placebo - 0.0%), diarrhea (1.8%, 1.1%), nausea (1.2%, 1.1%), hypoglycemia (1.2%, 0.0%) , vomiting (1.2%, 0.0%).

    At the 54th week of follow-up: adverse drug reactions observed with a frequency of ≥1% in the sitagliptin treatment group and in the bowl than in the combination therapy group with placebo: headache (sitagliptin - 2.4%, placebo - 0.0%), hypoglycemia (2.4%, 0.0%), upper respiratory tract infection (1.8%, 0.0%), nausea (1.2% 1.1%), cough (1.2%, 0.0%), fungal skin infection (1.2%, 0.0%), peripheral edema (1.2%, 0.0%), vomiting ( 1.2%, 0.0%).

    Combination with insulin

    In a 24-week, placebo-controlled study of combined sitagliptin therapy (at a daily dose of 100 mg) and a constant dose of insulin (with or without metformin) in the study drug group, compared to the placebo and insulin group (with or without metformin) the following undesirable phenomena: adverse drug reactions observed with a frequency of ≥1% in the sitagliptin treatment group and the bowl than in the insulin treatment group (with or without metformin): hypoglycemia (sitagliptin + insulin (with or without metformin) - 9.6%, placebo + insulin (with or without metformin) - 5.3%), influenza (1.2%, 0.3%), headache (1.2%, 0 , 0%).

    In another 24-week study in which patients received sitagliptin as an adjunct therapy for insulin therapy (with or without metformin), there were no undesirable reactions associated with taking the drug, with a frequency of ≥ 1% in the sitagliptin group (100 mg dose), and more often than in the placebo group.

    Pancreatitis

    In a generalized analysis of 19 double-blind, randomized clinical trials of the use of sitagliptin in a daily dose of 100 mg or the corresponding(active or placebo), the incidence of acute pancreatitis was 0.1 cases per 100 patient-years of treatment in each group (see "Precautions. Pancreatitis").

    Clinically significant deviations in vital signs or ECG (including the duration of the interval QTc) on the background of treatment with sitagliptin was not observed.

    Post-market observations

    In the course of post-marketing monitoring of the use of sitagliptin in monotherapy and / or combined therapy with other hypoglycemic agents, additional undesirable phenomena were identified. Since these data were obtained voluntarily from a population of undetermined size, the frequency and cause-and-effect relationship with the treatment of these undesirable phenomena can not be determined. These include: hypersensitivity reactions, including anaphylaxis, angioedema, rash, hives, skin vasculitis, exfoliative skin diseases, including Stevens-Johnson syndrome; acute pancreatitis, including hemorrhagic and necrotic forms with lethal and without lethal outcome; impairment of kidney function,including acute renal failure (sometimes dialysis is required); upper respiratory tract infection; nasopharyngitis; constipation; vomiting; headache; arthralgia; myalgia; pain in the limb; backache; itching; pemphigoid.

    Changes in laboratory indicators

    The frequency of deviations in laboratory parameters in the groups of treatment with sitagliptin (in a daily dose of 100 mg) was comparable with the frequency in the placebo groups. Most, but not all, of the clinical studies showed a slight increase in leukocyte count (approximately 200 / μL compared with placebo, with an average content of 6600 / μL at the beginning of treatment), due to an increase in the number of neutrophils.

    Analysis of clinical trial data showed a slight increase in the concentration of uric acid (approximately 0.2 mg / dl compared with placebo, mean pre-treatment concentration 5-5.5 mg / dL) in patients who received sitagliptin in a dose of 100 and 200 mg per day.

    There were no cases of gout development. There was a slight decrease in the concentration of total alkaline phosphatase (approximately 5 IU / L compared with placebo, average concentration before treatment 56-62 IU / L), partially associated with a slight decrease in the bone fraction of alkaline phosphatase.

    The listed changes in laboratory indicators are not considered clinically significant.

    Overdose:

    Symptoms: During clinical trials in healthy volunteers, there was good tolerability when taking sitagliptin in a single dose of 800 mg. Minimum interval changes QTc, not considered clinically significant, were noted in one study of the drug at the indicated dose. Clinical studies of the drug in a dose of more than 800 mg / day were not carried out.

    Treatment: removal of a nonabsorbed preparation from the LCG, monitoring of vital signs, including ECG, if necessary - conducting symptomatic and maintenance therapy.

    Sitagliptin slightly dialyzed. In clinical trials, only 13.5% of the dose was removed from the body during a 3-4 hour dialysis session. Prolonged dialysis can be prescribed in case of clinical necessity. There is no data on the efficacy of peritoneal dialysis of sitagliptin.

    Interaction:

    In studies of interactions with other drugs, sitagliptin had no clinically significant effect on the pharmacokinetics of the following drugs: metformin, rosiglitazone, glibenclamide,simvastatin, warfarin, oral contraceptives. Based on these data, sitagliptin does not inhibit isoenzymes CYP3A4, 2C8 or 2C9. Based on the data obtained in vitro, sitagliptin also probably does not inhibit CYP2D6, 1A2, 2C19 or 2B6, and also does not induce CYP3A4. A slight increase was noted AUC (11%), as well as the average Cm(18%) of digoxin when combined with sitagliptin. Ego increase is not considered clinically significant. It is not recommended to change the dose of either digoxin or sitagliptin when administered simultaneously.

    An increase was noted AUC and Cmand sitagliptin by 29% and 68%, respectively, in patients with co-administration of the drug in a single dose of 100 mg and cyclosporine (a potent inhibitor of p-glycoprotein) in a single dose of 600 mg. These changes pharmacokinetic parameters of sitagliptin are not considered clinically significant. It is not recommended to change the dose of the drug when combined with cyclosporine and other p-glycoprotein inhibitors (eg, ketoconazole).

    Population pharmacokinetic analysis in patients and healthy volunteers (n= 858) who received a wide range of concomitant drugs (n = 83, approximately half of which are excreted by the kidneys),did not reveal any clinically significant effect of drugs on the pharmacokinetics of sitagliptin.

    According to the population pharmacokinetic analysis of patients with type 2 diabetes, concomitant therapy did not have a clinically significant effect on the pharmacokinetics of sitagliptin. The study evaluated a number of drugs most commonly used by patients with type 2 diabetes, including: hypolipidemic drugs (statins, fibrates, ezetimibe), antiplatelet agents (clopidogrel), antihypertensive drugs (ACE inhibitors, angiotensin receptor antagonists II, beta-adrenoblockers, blockers of "slow" calcium channels, hydrochlorothiazide), non-steroidal anti-inflammatory drugs (naproxen, diclofenac, celecoxib), antidepressants (bupropion, fluoxetine, sertraline), antihistamines (cetirizine), proton pump inhibitors (omeprazole, lansoprazole) and drugs for the treatment of erectile dysfunction (sildenafil).

    Special instructions:

    Pancreatitis

    There have been reports of the development of acute pancreatitis, including hemorrhagic or necrotic with a lethal and non-lethal outcome, in patients taking sitagliptin (see section "Side effect").Patients should be informed of the characteristic symptoms of acute pancreatitis: persistent, severe abdominal pain. Clinical manifestations of pancreatitis disappeared after discontinuation of sitagliptin. In case of suspicion of pancreatitis, it is necessary to stop taking sitagliptin and other potentially dangerous drugs.

    Hypoglycaemia

    According to clinical studies of sitagliptin, the incidence of hypoglycemia in monotherapy or combination therapy with drugs that do not cause hypoglycemiametformin, pioglitazone), was comparable to the incidence of hypoglycemia in the placebo group. As with other hypoglycemic drugs, hypoglycemia was observed with the use of sitagliptin in combination with insulin or sulfonylurea derivatives (see, section "Side effect"). In order to reduce the risk of development of sulfone-induced hypoglycemia, the dose of the sulfonylurea derivative should be reduced (see section "Method of administration and dose").

    Application in the elderly

    In clinical trials, the effectiveness and safety of sitagliptin in elderly patients (≥65 years,409 patients) were comparable to those in patients younger than 65 years of age. Dose adjustment according to age is not required. Older patients are more likely to develop kidney failure. Accordingly, as in other age groups, dose adjustment is necessary in patients with severe renal failure (see "Method of administration and dose").

    Effect on the ability to drive transp. cf. and fur:There have been no studies to study the effect of sitagliptin on the ability to drive vehicles. Nevertheless, no negative effect of sitagliptin on the ability to drive vehicles or complex mechanisms is expected.
    Form release / dosage:

    Film-coated tablets, 25 mg, 50 mg, 100 mg.

    Packaging:

    For 7 tablets in a contour mesh box made of polyvinylchloride film and aluminum foil printed lacquered.

    For 14, 28, 56, 84 or 98 tablets in a polymer can of polyethylene with a cover pulled with the control of the first opening. Free space is filled with cotton wool. Labels are applied to cans from paper label or written or from polymeric materials, self-adhesive.

    For 2, 4 or 8 contour mesh packages together with the instruction for use are placed in a pack of cardboard for consumer packaging.

    On 1 bank together with the instruction on application place in a pack from a cardboard for consumer tare.

    Storage conditions:

    AT protected from light at a temperature of no higher than 25 ° C.

    Keep out of the reach of children.

    Shelf life:

    3 years. Do not use after the expiration date.

    Terms of leave from pharmacies:On prescription
    Registration number:LP-004566
    Date of registration:01.12.2017
    Expiration Date:01.12.2022
    The owner of the registration certificate:Pharmasintez-Tyumen, Open CompanyPharmasintez-Tyumen, Open Company Russia
    Manufacturer: & nbsp
    Information update date: & nbsp18.12.2017
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