Januvia® (Januvia) - instructions for use, composition, drug analogues, dosage, side effects

Composition

Film Coated Tablets

Active substance:

• sitagliptin phosphate monohydrate
• (equivalent to 25/50/100 mg of sitagliptin)
• excipients: MCC - 30.94 / 61.88 / 123.8 mg; unground ground calcium phosphate - 30.94 / 61.88 / 123.8 mg; croscarmellose sodium - 2/4/8 mg; magnesium stearate - 1/2/4 mg; sodium fumarate - 3/6/12 mg
• film cover (for dosing 25 mg): Opadry® II pink 85F97191 (polyvinyl alcohol - 40%, titanium dioxide (E171) - 24.142%, macrogol 3350 (PEG) - 20.2%, talc - 14.87%, iron dye yellow oxide (E172) - 0.579%, iron dye red oxide (E172) - 0.209% - 4 mg
• film cover (for dosage of 50 mg): Opadry® II light beige 85F17498 (polyvinyl alcohol - 40%, titanium dioxide (E171) - 24.142%, macrogol 3350 (PEG) - 20.2%, talc - 14.8%, iron dye yellow oxide (E172) - 0.765%, iron dye red oxide (E172) - 0.093%) - 8 mg
• film cover (for dosage of 100 mg): Opadry® II beige 85F17438 (polyvinyl alcohol - 40%, titanium dioxide (E171) - 21.56%, macrogol 3350 (PEG) - 20.2%, talc - 14.8%, iron dye yellow oxide (E172) - 3.07%, iron dye red oxide (E172) - 0.37% - 16 mg

Description of the dosage form

Tablets, 25 mg: round, biconvex, light pink in color with a faint beige shade, film-coated, with "221" engraving on one side and smooth on the other.

Tablets, 50 mg: round, biconvex, light beige, film coated, engraved with "112" on one side and smooth on the other.

Tablets, 100 mg: round, biconvex, beige, film coated, engraved with "277" on one side and smooth on the other.

Pharmachologic effect

Pharmacological action - hypoglycemic.

Pharmacodynamics

The drug Januvia® (sitagliptin) is active when taken orally, a highly selective inhibitor of the enzyme DPP-4, intended for the treatment of type 2 diabetes. receptors activated by proliferator peroxisome (PPAR-γ), alpha-glucosidase inhibitors, amylin analogues. Inhibiting DPP-4, sitagliptin increases the concentration of two hormones of the incretin family: GLP-1 and HIP. Hormones of the family of incretins are secreted in the intestine during the day, their concentration increases in response to food intake. Incretins are part of the internal physiological system for regulating glucose homeostasis. At normal or elevated blood glucose concentrations, hormones of the incretin family contribute to an increase in insulin synthesis, as well as its secretion by pancreatic beta cells, due to signaling intracellular mechanisms associated with cAMP.

GLP-1 also contributes to the suppression of increased glucagon secretion by pancreatic alpha cells. A decrease in glucagon concentration against the background of an increase in insulin concentration contributes to a decrease in glucose production by the liver, which ultimately leads to a decrease in glycemia. This mechanism of action differs from the mechanism of action of sulfonylurea derivatives, which stimulate the release of insulin and with a low concentration of glucose in the blood, which is fraught with the development of sulfonase-induced hypoglycemia not only in patients with type 2 diabetes, but also in healthy individuals.

At a low concentration of glucose in the blood, the listed effects of incretins on insulin release and a decrease in glucagon secretion are not observed. GLP-1 and HIP do not affect the release of glucagon in response to hypoglycemia. Under physiological conditions, the activity of incretins is limited by the enzyme DPP-4, which quickly hydrolyzes the incretins to form inactive products.

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

In patients with type 2 diabetes, taking one dose of Januvia® leads to inhibition of the activity of DPP-4 enzyme for 24 hours, which leads to an increase of 2-3 times in the concentration of circulating GLP-1 and HIP incretin, plasma concentrations of insulin and C -peptide, reducing the concentration of glucagon in the blood plasma, reducing fasting glucose, as well as after loading glucose or food load.

A study assessing the cardiovascular safety of sitagliptin (TECOS). In a study assessing the cardiovascular safety of sitagliptin (TECOS), patients took Januvia® 100 mg per day (or 50 mg per day if the initial calculated GFR (eGFR) was ≥30 and <50 ml / min / 1.73 m2 ) or placebo, which were added to standard therapy according to existing national standards for determining target HbA1C levels and controlling cardiovascular risk factors. At the end of the average follow-up period of 3 years, in patients with type 2 diabetes, taking Januvia®, in addition to standard treatment, did not increase the risk of serious adverse events from the cardiovascular system (risk ratio - 0.98; 95% CI: 0.89 –1.08; p <0.001 to prove the absence of superiority) or the risk of hospitalization due to heart failure (risk ratio - 1; 95% CI: 0.83–1.2; p = 0.98 for the difference in risk frequency), by compared with standard treatment without additional intake of Januvia®.

Pharmacokinetics

The pharmacokinetics of sitagliptin is comprehensively described in healthy individuals and patients with type 2 diabetes. In healthy individuals, after oral administration of 100 mg of sitagliptin, rapid absorption of the drug is observed, reaching Cmax in the range from 1 to 4 hours after administration. AUC increases in proportion to the dose and in healthy subjects is 8.52 µmol · h / L when taken 100 mg orally, Cmax was 950 nmol / L. Plasma AUC of sitagliptin increased by approximately 14% after the next dose of 100 mg of the drug to achieve Css after taking the first dose. The intra-and intersubjective coefficients of variation of the AUC of sitagliptin were insignificant.

Absorption. The absolute bioavailability of sitagliptin is approximately 87%. Since the joint intake of the drug Januvia® and fatty foods does not have an effect on the pharmacokinetics, the drug Januvia® can be administered regardless of the meal.

Distribution. The average Vss after a single dose of 100 mg of sitagliptin in healthy volunteers is approximately 198 liters. The fraction of sitagliptin binding to plasma proteins is relatively low at 38%.

Metabolism. Approximately 79% of sitagliptin is excreted unchanged by the kidneys. Only a small fraction of the drug ingested is metabolized. After the introduction of 14C-labeled sitagliptin inside about 16% of the radioactive sitagliptin excreted in the form of its metabolites. Traces of 6 sitagliptin metabolites, probably not having DPP-4 inhibitory activity, were found. In vitro studies have revealed that the primary isoenzymes involved in limited sitagliptin metabolism are CYP3A4 and CYP2C8.

Inference. After the introduction of 14C-labeled sitagliptin inside healthy volunteers, approximately 100% of the administered sitagliptin was derived as follows: 13% through the intestine, 87% through the kidneys within one week after taking the drug. The average T1 / 2 of sitagliptin when administered orally with 100 mg was approximately 12.4 hours; renal clearance of approximately 350 ml / min.

Sitagliptin removal is carried out primarily by excretion by the kidneys by the mechanism of active tubular secretion. Sitagliptin is a substrate for a transporter of organic human anions of the third type (hOAT-3), which may be involved in the process of elimination of sitagliptin by the kidneys. Clinically, hOAT-3 involvement in the transport of sitagliptin has not been studied. Sitagliptin is also a substrate of P-gp, which can be involved in the process of excretion of sitagliptin by the kidneys. However, cyclosporine, which is an inhibitor of P-gp, did not reduce the renal clearance of sitagliptin.

Special patient groups

Renal failure. An open study of the drug Januvia® 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 the following groups: patients with mild renal insufficiency (Cl creatinine 50 to 80 ml / min), moderate (Cl creatinine 30 to 50 ml / min) and severe renal insufficiency (Cl creatinine less than 30 ml / min), as well as with terminal stage of chronic kidney disease, in need of dialysis.

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

An increase in SUC of Sitagliptin by approximately 2 times compared with the control group was observed in patients with moderate renal insufficiency; approximately fourfold increase in AUC was observed in patients with severe renal insufficiency, as well as in patients with end-stage CRF compared with the control group. Sitagliptin was slightly removed by hemodialysis: only 13.5% of the dose was removed from the body during the 3-4 hour dialysis session.

Thus, to achieve a therapeutic concentration of sitagliptin in the blood plasma (similar to that in patients with normal renal function) in patients with moderate and severe renal insufficiency, dose adjustment is required (see "Dosage and Administration").

Liver failure. In patients with moderate liver failure (7–9 points on the Child-Pugh scale), the average AUC and Cmax of sitagliptin in a single dose of 100 mg increase by approximately 21 and 13%, respectively. Thus, the dose adjustment of the drug for mild and moderate liver failure is not required.

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

Elderly age. The age of the patients had no clinically significant effect on the pharmacokinetic parameters of sitagliptin. Compared with young patients, in elderly patients (65–80 years old), the concentration of sitagliptin is approximately

Indications drug Januvia®

• monotherapy, addition to diet and exercise to improve glycemic control in patients with type 2 diabetes.
• in combination with metformin in patients with type 2 diabetes mellitus to improve glycemic control as a starting therapy or when diet and exercise combined with monotherapy with one of these drugs does not lead to adequate glycemic control;
• in combination with sulfonylurea derivatives in patients with type 2 diabetes mellitus to improve glycemic control when diet and exercise combined with monotherapy with one of the listed drugs does not lead to adequate glycemic control;
• in combination with PPAR-γ agonists (thiazolidinediones) in patients with type 2 diabetes mellitus to improve glycemic control when diet and exercise combined with monotherapy with one of the listed drugs does not lead to adequate glycemic control;
• in combination with metformin and sulfonylurea derivatives in patients with type 2 diabetes mellitus to improve glycemic control when diet and exercise combined with therapy with two of these drugs do not lead to adequate glycemic control;
• in combination with metformin and PPAR-γ agonists (thiazolidinediones) in patients with type 2 diabetes mellitus to improve glycemic control when diet and exercise combined with therapy with two of these drugs do not lead to adequate glycemic control;
• as a supplement to insulin (with or without metformin) in patients with type 2 diabetes in cases where diet, exercise, and a stable insulin dose do not lead to adequate glycemic control.

Contraindications

• hypersensitivity to any of the components of the drug;
• type 1 diabetes;
• diabetic ketoacidosis;
• pregnancy;
• breastfeeding period;
• age up to 18 years.

With care: renal failure, pancreatitis.

Use during pregnancy and lactation

There were no controlled studies of Januvia® in pregnant women, therefore, there are no data on the safety of its use in pregnant women. The drug Januvia®, like other oral hypoglycemic drugs, is not recommended for use during pregnancy.

There are no data on the allocation of sitagliptin with breast milk. Therefore, the drug Januvia® should not be administered during lactation.

Side effects

The drug Januvia® is generally well tolerated both in the monotherapy regimen and in combination with other hypoglycemic drugs. In clinical trials, the overall incidence of adverse events, as well as the frequency of discontinuation of the drug due to adverse events, were similar to those taken with placebo.

According to 4 placebo-controlled studies (duration 18-24 weeks) of Januvia® in a daily dose of 100-200 mg as a mono- or combination therapy with metformin or pioglitazone, no adverse reactions associated with the studied drug were observed, the frequency of which exceeded 1 % in the group of patients taking the drug Januvia®. 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 during the above clinical studies showed that the overall incidence of hypoglycemia in patients taking Januvia® was similar to that taken with placebo (Januvia® 100 mg - 1.2%, Januvia® 200 mg - 0 , 9%, placebo - 0.9%). The frequency of adverse events observed by the gastrointestinal tract when taking Januvia® in both doses was similar to that taken with placebo (except for more frequent nausea while taking Januvia® at a dose of 200 mg / day): abdominal pain (Januvia® 100 mg - 2.3%, Januvia® 200 mg - 1.3%, placebo - 2.1%), nausea (1.4; 2.9; 0.6%), vomiting (0.8; 0.7, 0.7; 0.9%), diarrhea (3; 2.6; 2.3%).

In all studies, adverse reactions in the form of hypoglycemia were recorded based on all reports of clinically significant symptoms of hypoglycemia; parallel measurement of the concentration of glucose in the blood is not required.

Starting combination therapy with metformin

In a 24-week placebo-controlled factorial study of starting combination therapy with Januvia® at 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 × 2 times a day) in the combined group The following adverse events associated with taking the drug were observed with treatment compared with the metformin monotherapy group, with a frequency of ≥1% in the Januvia® treatment group and more often than in the metformin treatment group in monotherapy: diarrhea (Januvia® + metformin - 3.5% m etformin - 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 sulfonylurea derivatives or sulfonylurea derivatives and metformin

In a 24-week placebo-controlled study of combination therapy with Januvia® (100 mg daily dose) and glimepiride or glimepiride and metformin in the group of the study drug compared with the group of patients taking placebo and glimepiride or glimepiride and metformin, the following undesirable effects were observed taking the drug, with a frequency of ≥1% in the treatment group with Januvia® and more often than in the combination therapy group with placebo: hypoglycemia (Januvia® - 9.5%, placebo - 0.9%).

Starting combination therapy with PPAR-γ agonists

In a 24-week study of starting combination therapy with Januvia® at a daily dose of 100 mg and pioglitazone at a daily dose of 30 mg in the combined treatment group compared with monotherapy with pioglitazone, the following adverse events associated with the use of the drug were observed, with a frequency of ≥1% in the group treatment with Januvia® and more often than in the pioglitazone treatment group in monotherapy: asymptomatic decrease in blood glucose concentration (Januvia® + pioglitazone - 1.1%, pioglitazone - 0%), symptomatic hypoglycem iya (0.4; 0.8%).

Combination with agonists PPAR-γ and metformin

According to a placebo-controlled study for treatment with Januvia® (100 mg daily dose) in combination with rosiglitazone and metformin in the study group compared with the group of patients taking placebo with rosiglitazone and metformin, the following adverse events associated with taking the drug were observed. with a frequency of ≥1% in the treatment group with Januvia® and more often than in the combination group with placebo: at 18 weeks of observation - headache (Januvia® - 2.4%, placebo - 0%), diarrhea (1.8; 1.1%), nausea (1.2; 1.1%), hypo likemiya (1,2; 0%), vomiting (1.2, 0%); at 54 weeks of observation - headache (Januvia® - 2.4%, placebo - 0%), hypoglycemia (2.4; 0%), upper respiratory tract infections (1.8; 0%), nausea (1.2 ; 1.1%), cough (1.2; 0%), fungal infection of the skin (1.2; 0%), peripheral edema (1.2; 0%), vomiting (1.2; 0%).

Insulin combination

In a 24-week, placebo-controlled study of combination therapy with Januvia® (100 mg daily dose) and a fixed dose of insulin (with or without metformin) in the group of the study drug compared with the group of patients taking placebo and insulin (with or without metformin) , the following adverse events associated with taking the drug were observed, with a frequency of ≥1% in the treatment group of Januvia® and more often than in the insulin treatment group (with or without metformin): hypoglycemia (Januvia® + insulin (with or without metformin) - 9.6%, placebo + and nsulin (with or without metformin) - 5.3%), influenza (1.2; 0.3%), headache (1.2; 0%).

In another 24-week study in which patients received Januvia® as an adjunctive therapy for insulin therapy (with or without metformin), no adverse reactions associated with the drug were detected, with a frequency of ≥1% in the Januvia® treatment group (at a dose of 100 mg) and more often than in the placebo group.

Pancreatitis

In a generalized analysis of 19 double-blind, randomized clinical studies using sitagliptin at a daily dose of 100 mg or an appropriate control drug (active or placebo), the incidence of unconfirmed acute pancreatitis was 0.1 cases per 100 patient-years of treatment in each group (see "Special instructions ", Pancreatitis, as well as a study on the cardiovascular safety of sitagliptin (TECOS) below).

Clinically significant deviations of vital signs or ECG (including the duration of the QTc interval) were not observed during treatment with Januvia®.

Study assessing cardiovascular safety of sitagliptin (TECOS)

The study on the evaluation of the cardiovascular safety of sitagliptin (TECOS) included 7332 patients with type 2 diabetes who were taking Januvia® 100 mg per day (or 50 mg per day if the baseline GFRT was ≥30 and <50 ml / min / 1.73 m2), and 7339 patients who took placebo in the general population of patients who were prescribed treatment. The study drug (Januvia® or placebo) was added to standard therapy according to existing national standards for choosing a target HbA1C level and controlling cardiovascular risk factors. A total of 2004 patients 75 years and older were included in the study (970 took Januvia® and 1034 - placebo). The overall incidence of serious adverse events in patients taking Januvia® was the same as in patients taking placebo. An assessment of complications related to diabetes mellitus previously indicated for tracking revealed a comparable incidence of adverse events between groups, including infections (18.4% in patients taking Januvia®, and 17.7% in patients taking placebo) and impaired function kidney disease (1.4% in patients taking Januvia®, and 1.5% in patients taking placebo). The profile of adverse events in patients 75 years and older was generally similar to that for the general population.

In the population of patients intention-to-treat (patients who took at least one dose of the study drug), among those who initially received insulin therapy and / or sulfonylurea drugs, the incidence of severe hypoglycemia was 2.7% in patients taking the drug Januvia ®, and 2.5% in patients taking placebo. Among patients initially not receiving insulin and / or sulfonylureas, the incidence of severe hypoglycemia was 1% in patients taking Januvia® and 0.7% in patients taking placebo. The incidence of pancreatitis confirmed by the examination was 0.3% in patients taking Januvia® and 0.2% in patients taking placebo. The incidence of confirmed by the examination of cases of malignant tumors was 3.7% in patients taking the drug Januvia®, and 4% in patients taking placebo.

Post-registration observations

During the post-registration monitoring of the use of the drug Januvia® in monotherapy and / or in combination therapy with other hypoglycemic agents, additional adverse events have been identified. Since these data were obtained voluntarily from a population of uncertain size, it is impossible to determine the frequency and causal relationship with the therapy of these adverse events. These include hypersensitivity reactions, incl. anaphylaxis, angioedema, rash, urticaria, cutaneous vasculitis, exfoliative skin diseases, including Stevens-Johnson syndrome; acute pancreatitis, including hemorrhagic and necrotic forms with a lethal and non-fatal outcome; deterioration of renal function, including acute renal failure (dialysis is sometimes required); upper respiratory tract infections; nasopharyngitis; constipation; vomiting; headache; arthralgia; myalgia; limb pain; backache; itching; pemphigoid.

Changes in laboratory parameters

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

Analysis of the data of clinical studies of the drug showed a slight increase in the concentration of uric acid (approximately 0.2 mg / dL compared to placebo, the average concentration before treatment of 5-5.5 mg / dL) in patients receiving the drug Januvia® at a dose of 100 and 200 mg / day No cases of gout have been reported.

There was a slight decrease in the concentration of total alkaline phosphatase (approximately 5 IU / L compared with placebo, the average concentration before treatment was 56–62 IU / L), partly due to a slight decrease in the bone fraction of alkaline phosphatase.

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

Interaction

In studies on the interaction with other drugs, sitagliptin did not have a 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 CYP3A4, CYP2C8 or CYP2C9 isoenzymes. Based on in vitro data, sitagliptin also does not inhibit CYP2D6, CYP1A2, CYP2C19 and CYP2 isoenzymes B6 and does not induce the CYP3A4 isoenzyme.

Repeated administration of metformin in combination with sitagliptin did not significantly affect the pharmacokinetic parameters of sitagliptin in patients with type 2 diabetes.

According to a population-based pharmacokinetic analysis of type 2 diabetes patients, concomitant therapy did not have a clinically significant effect on sitagliptin pharmacokinetics. The study evaluated a number of drugs most commonly used by patients with type 2 diabetes, including lipid-lowering drugs (statins, fibrates, ezetimibe), antiaggregants (clopidogrel), anti-hypertensive drugs (ACE inhibitors, ARA II, beta-adrenergic blockers, BPC, hydrochlorothiazide), NSAIDs (naproxen, diclofenac, celecoxib,), I did not use this type of intervention, I am not using this type of interventions, celecoxib, an anti-hypertensives, naproxen, diclofenac, antioxidant drugs , antihistamines (cetirizine), proton pump inhibitors (omeprazole, lansoprazole) and drugs for the treatment of erectile dysfunction (sildenafil).

There was a slight increase in AUC (11%), as well as the average Cmax (18%) of digoxin when used together with sitagliptin. This increase is not considered clinically significant. It is not recommended to change the dose of either digoxin or Januvia® when combined.

An increase in AUC and Cmax of Januvia® was noted by 29 and 68%, respectively, in patients with a combined oral dose of 100 mg of Januvia® and a single oral dose of 600 mg of cyclosporine, a powerful inhibitor of P-gp. The observed changes in the pharmacokinetic characteristics of sitagliptin are not considered clinically significant. It is not recommended to change the dose of the drug Januvia® when used together with cyclosporine and other P-gp inhibitors (including ketoconazole).

A population-based pharmacokinetic analysis of patients and healthy volunteers (n = 858) for a wide range of concomitant medications (n ​​= 83, about half of which are excreted by the kidneys) did not reveal any clinically significant effects of these substances on the pharmacokinetics of sitagliptin.

Dosage and administration

Inside. The recommended dose of Januvia® is 100 mg / day by mouth as monotherapy or in combination with metformin, or sulfonylurea derivatives, or PPAR-γ agonists (thiazolidinediones), or insulin (with or without metformin), or in combination with metformin and sulfonylurea , or metformin and PPAR-γ agonists.

The drug Januvia® can be taken regardless of the meal. The dosage regimen of metformin, sulfonylurea derivatives and PPAR-γ agonists should be selected on the basis of the recommended doses for these drugs.

When combining the drug Januvia® with sulfonylurea derivatives or insulin, it is advisable to reduce the traditionally recommended dose of a sulfonylurea or insulin derivative to reduce the risk of developing sulfonue-induced or insulin-induced hypoglycemia (see "Special instructions". Hypoglycemia).

If the patient missed taking Januvia®, the drug should be taken as soon as possible after the patient remembers the missed dose.

Do not take a double dose of Januvia® on the same day.

Special patient groups

Renal failure. Patients with mild renal insufficiency (Cl creatinine ≥50 ml / min, approximately corresponding to serum creatinine concentrations ≤ 1.7 mg / dl in men and ≤ 1.5 mg / dl in women) do not require dose adjustment of Januvia®.

For patients with moderate renal insufficiency (Cl creatinine ≥30 ml / min, but <50 ml / min, approximately corresponding to serum creatinine concentrations > 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 Januvia® is 50 mg / day.

For patients with severe renal failure (Cl creatinine <30 ml / min, approximately corresponding to serum creatinine concentrations> 3 mg / dL for men and> 2.5 mg / dL for women) or with end-stage CRF requiring hemodialysis or peritoneal dialysis, the dose of Januvia® is 25 mg / day. The drug Januvia® can be used regardless of the schedule of the dialysis procedure.

In view of the need for dose adjustment, it is recommended that patients with renal insufficiency should assess their renal function before starting treatment with Januvia® and periodically during the treatment process.

Liver failure. No dose adjustment of the drug Januvia® is required in patients with mild or moderate liver failure. The drug has not been studied in patients with severe liver failure.

Elderly age. No dose adjustment is required for Januvia® in elderly patients.

Overdose

During clinical studies in healthy volunteers, a single dose of 800 mg of Januvia® was generally well tolerated. Minimal changes in the QTc interval, which are not considered clinically significant, were noted in one of the studies of the drug Januvia® at a dose of 800 mg / day. A dose of over 800 mg / day has not been studied in humans.

In the first phase of clinical studies, no adverse reactions related to the treatment with Januvia® when taking the drug in a daily dose of 400 mg for 28 days were noted.

Treatment: it is necessary to start standard maintenance activities - removal of unabsorbed drug from the gastrointestinal tract, monitoring of vital signs, including ECG, as well as the appointment of maintenance therapy, if required.

Sitagliptin is poorly dialyzed. In clinical studies, only 13.5% of the dose was removed from the body during the 3-4 hour session of dialysis. Prolonged dialysis may be prescribed in cases of clinical need. There is no data on the effectiveness of peritoneal dialysis of sitagliptin.

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 "Side Effects"). Patients should be informed about the characteristic symptoms of acute pancreatitis - persistent, severe abdominal pain. Clinical manifestations of pancreatitis disappeared after cessation of sitagliptin. If pancreatitis is suspected, it is necessary to stop taking Januvia® and other potentially dangerous drugs.

Hypoglycemia. According to clinical studies of Januvia®, the incidence of hypoglycemia in monotherapy or combination therapy with drugs that do not cause hypoglycemia (metformin, pioglitazone) was comparable to the incidence of hypoglycemia in the placebo group. As in the case of taking other hypoglycemic drugs, hypoglycemia was observed with the use of the drug Januvia® in combination with insulin or sulfonylurea derivatives (see "Side Effects"). In order to reduce the risk of sulfoning-induced hypoglycemia, the dose of a sulfonylurea derivative should be reduced (see "Dosage and Administration").

Use in the elderly. In clinical studies, the efficacy and safety of Januvia® in elderly patients (≥65 years, 409 patients) were comparable with these indicators in patients younger than 65 years. Dose adjustment depending on age is not required. Elderly patients are more likely to develop renal failure. Accordingly, as in other age groups, dose adjustment is necessary in patients with severe renal insufficiency (see "Dosage and Administration").

Influence on ability to drive vehicles and mechanisms. No studies have been conducted to study the effect of Januvia® on the ability to drive. However, the negative impact of Januvia® on the ability to drive vehicles or complex mechanisms is not expected.

Release form

Tablets, film coated, 25 mg, 50 mg, 100 mg. At 14 tab. in a blister of PVDC / PE / PVC film and aluminum foil. On 1, 2, 4, 6 or 7 bl. placed in a carton box.

In the case of production at AKRIKHIN JSC

Tablets, film coated, 100 mg. At 14 tab. in a blister of PVDC / PE / PVC film and aluminum foil. 2 bl. placed in a carton box.

Symptoms of type 2 diabetes

Are you worried that you or some of your loved ones have symptoms of type 2 diabetes? Every day we communicate with people with newly diagnosed diabetes and understand what emotions accompany this initial period - it is rather difficult to come to terms with a new diagnosis.

Very often, people develop the main symptoms of type 2 diabetes, but there is no diabetes, so you should not try to diagnose yourself. On the other hand, the anxiety and feeling of helplessness that you have when you are looking for information for a loved one is difficult to handle, so getting the right information and support is the best solution. In any case, we advise you to consult a doctor so that you can pass all the necessary tests on time.

Briefly considering the symptoms of type 2 diabetes, you can distinguish 3 main ones:

1. Excessive thirst
   This condition is also known as polydipsia; in essence, it is a continuing desire to drink water despite the use of an adequate amount of it throughout the day.
2. Excessive Hunger
   By analogy with polydipsia, this symptom is called polyphagy. Continued increased hunger against a background of lack of physical activity can be an indicator of the presence of problems in the body.
3. Frequent urination
   The last of the three main symptoms and the last "P" is polyuria. It can be described as unusual or irregular urination, which retains this character day after day.

Neglecting the signs and symptoms of type 2 diabetes

If you are concerned about your current state of health, self-education is the right decision. Unfortunately, many people ignore the warning signals and symptoms of type 2 diabetes.

Early detection of diabetes is important because it limits the potential for harm. If the symptoms of type 2 diabetes are ignored and the final diagnosis is made at a later stage, complications can occur, for example:

• Neuropathy
  A disease or lesion of one or more peripheral nerves, usually causing numbness or a decrease in muscle strength.
• Retinopathy
  This is a disease of the retina that causes impairment or loss of vision.
• Nephropathy
  Diabetic nephropathy is a progressive kidney disease caused by damage to the capillaries in the glomeruli.

Other common symptoms of type 2 diabetes include:

• Weight loss
  Despite increased appetite and eating large amounts of food, people with diabetes often notice that their weight is decreasing. Since type 2 diabetes is characterized by a lack of ability to absorb glucose, the body is looking for other sources of energy - stored fat.
• Blurry vision
  Often occurs due to the constantly persistent high blood sugar levels, which leads to swelling of the lens. Exposure to high blood sugar levels means that the lens loses its ability to effectively change shape, so vision becomes blurred, and muscles work with great effort, trying to maintain focus.
• Foot pain or numbness of the limbs
  Diabetic polyneuropathy is associated with prolonged exposure to high blood sugar levels in the body.
• Itching
  It is usually found in the male and female genital organs and is often associated with candidiasis (thrush).
• Candidiasis (thrush) and frequent infections
  All of us, even those who do not have diabetes, have certain bacteria in their bodies, including yeast. However, they may become more aggressive in patients with diabetes, because high blood sugar levels create more favorable conditions for the growth of yeast fungi.
• Weakness after eating
  Leading symptom of diabetes. Its appearance is due to the fact that the body hardly processes glucose (sugar).
• Dryness and tingling in the skin
  A lack of gamma-linoleic acid (GLA) in diabetic patients can often lead to lesions of the legs, feet, and hands.

Differences in the symptoms of type 2 diabetes in adults and children

The symptoms of type 2 diabetes in children and adults are very similar. However, it will be difficult for a child to notice obvious signs and effectively communicate his feelings, so it is very important that his relatives understand the essence of diabetes and its most important symptoms.

Type 2 diabetes in children

Unfortunately, type 2 diabetes is no longer a disease that affects only the adult population. Over the past 20 years, type 2 diabetes in children has ceased to be rare, and the number of children with this disease is growing every year. According to forecasts, by 2025 about 5 million people will suffer from diabetes, of which 4.5 million will have type 2 diabetes - many of them will be children and young adults.

Fortunately, type 2 diabetes in children is less common than type 1. Recent studies have shown that the growing prevalence of obesity in children and type 2 diabetes are related. Thus, it becomes clear that taking care of the nutrition and lifestyle of a child is the surest way to avoid diabetes.

Although obesity in children is a relatively new problem and research has not yet been carried out on the determining factors and causes, available data point to family habits and education. Formation of a healthy, varied diet and regime, including physical activity, from an early age lays a good foundation for a healthy life and, in addition, helps prevent diseases. Since overweight and obese children are likely to grow up in adults with obesity, the cycle of unhealthy lifestyles is unlikely to break, which means that new generations of children with a high risk of developing diabetes will appear.

What children are at risk for developing type 2 diabetes?

Protecting your loved ones is a natural impulse, and we understand that you always wish your child the best. As the above study shows, over 95% of all children and adolescents with type 2 diabetes are overweight and about 83% are clinical obesity. The desire to make children as active and healthy as possible greatly reduces the risk of type 2 diabetes.

It was found that ethnicity can influence the likelihood of making a diagnosis of type 2 diabetes. Studies have shown that people of African and Creole descent have a 3-fold higher risk of this disease, and people from South Asia are almost 6 times more likely.

If your child belongs to one of these groups, this is not a reason to worry, because genetics is a factor that we cannot influence, and stress and panic will not help here. Even in the worst case, type 2 diabetes can be controlled, and the development of medical technology enables us to provide more convenient methods for insulin delivery and support.

If you want to discuss a specific question with a Medtronic consultant, contact the MiniMed Care team.

Symptoms of type 2 diabetes in children

Very often in children, the symptoms of diabetes do not manifest themselves fully until the diagnosis is finally established. This is because children’s blood sugar levels slowly increase as they get older, as a result of which they fall out of sight. However, the most common symptoms in children are:

• Increased urination.
  If your child develops bedwetting and he often uses the toilet during the day, this may be a sign of diabetes.
• Reinforced thirst.
  Children often run and exercise during the game, so they can consume a lot of water. But if you notice that the child is still asking for water or other beverages, although there was no physical exertion, this can be a warning sign.

Type 2 diabetes in children can also manifest other symptoms, including:

• Increased fatigue
• Weight loss
• Nausea
• Frequent infections, slow healing of wounds and suppuration
• Blurry vision

Difficulties faced by children with diabetes

Diabetes type 2 in children is very similar in its symptoms to diabetes in adults, but the difficulties faced by children are radically different. The diagnosis of diabetes entails new responsibilities and factors that need to be taken into account - something that a child in a normal situation would never have thought about.

Supporting someone from a parent or loved one can help a child lead a full and healthy life. It begins with effective disease information to help figure out how to manage the condition and how to recognize warning signals before potential attacks of hypoglycemia / hyperglycemia.

Injecting at such a young age can be difficult for most children, so an insulin pump can help. A significant reduction in hemoglobin HbA1c levels in patients with type 2 diabetes when using an insulin pump has been clinically proven.