Velmetia pills 850mg +50mg, 56pcs

Composition

Active ingredients:

sitagliptin phosphate monohydrate 64.25 mg (equivalent to 50 mg of sitagliptin) and metformin hydrochloride 850 mg.

Auxiliary substances:

microcrystalline cellulose 96.64 mg,

povidone K-29/32 78.19 mg,

sodium stearyl fumarate 22.34 mg,

sodium lauryl sulfate 5.585 mg;

Opadray® II pink tablet shell,85F94182 (27.93 mg) contains:

polyvinyl alcohol 49.950%,

titanium dioxide (E 171) 6,000%,

macrogol 3350 (polyethylene glycol) 25.210%,

talc 18.470%,

iron oxide black (E 172) 0.020%,

iron oxide red (E 172) 0.350%.

Pharmacological action

Pharmacotherapy group: Hypoglycemic agent for oral use combined (dipeptidyl peptidase-4-inhibitor + biguanide)ATX: A. 10. B. D Combination of biguanides and sulfonylureas. 10. B. D. 07 Metformin and Sitagliptin Pharmacodynamics : Velmetiya® is a combination of two hypoglycemic drugs with a complementary mechanism of action, designed to improve glycemic control in patients with type 2 diabetes mellitus: sitagliptin. an inhibitor of the enzyme dipeptidyl peptidase-4 (DPP-4), and metformin, a representative of the biguanide class. Sitagliptin is an orally active, highly selective DPP-4 inhibitor intended for the treatment of type 2 diabetes mellitus. The pharmacological effects of a class of DPP-4 inhibitors are mediated by incretin activation. By inhibiting DPP-4, sitagliptin increases the concentration of two known active hormones of the incretin family: glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). Incretins are part of the internal physiological system for regulating glucose homeostasis. At normal or elevated blood glucose concentrations, GLP-1 and GIP promote increased insulin synthesis and secretion by pancreatic beta cells. GLP-1 also suppresses glucagon secretion by pancreatic alpha cells, thus reducing glucose synthesis in the liver. This mechanism of action differs from the mechanism of action of sulfonylurea derivatives, which stimulate the release of insulin even at low blood glucose concentrations, which is fraught with the development of sulfonyl-induced hypoglycemia not only in patients with type 2 diabetes, but also in healthy individuals. Being a highly selective and effective inhibitor of the DPP-4 enzyme, sitagliptin at therapeutic concentrations does not inhibit the activity of related DPP-8 or DPP-9 enzymes. Sitagliptin differs in chemical structure and pharmacological action from analogues of GLP-1, insulin, sulfonylurea derivatives or meglitinides, biguanides, agonists of gamma-receptors activated by the peroxisome proliferator (PPARy), alpha-glycosidase inhibitors and amylin analogues. Metformin Metformin is a hypoglycemic drug that increases glucose tolerance in patients with type 2 diabetes mellitus, reducing basal and postprandial blood glucose concentrations. Its pharmacological mechanisms of action differ from those of oral hypoglycemic drugs of other classes. Metformin reduces glucose synthesis in the liver, reduces intestinal glucose absorption, and increases insulin sensitivity by enhancing peripheral glucose uptake and utilization. Unlike sulfonylurea derivatives, metformin does not cause hypoglycemia in patients with type 2 diabetes mellitus or in healthy people (except in certain circumstances, see the section ” With caution. Metformin”) and does not cause hyperinsulinemia. During treatment with metformin, insulin secretion does not change, while the fasting insulin concentration and the daily value of the plasma insulin concentration may decrease. Oral use of a single dose of sitagliptin in patients with type 2 diabetes mellitus leads to suppression of the activity of the DPP-4 enzyme for 24 hours, which is accompanied by a twofold increase in the concentration of circulating active GLP-1 and GIP, an increase in the plasma concentration of insulin and C-peptide, a decrease in the concentration of glucagon and fasting plasma glucose, as well as a decrease in the amplitude of glycemic fluctuations after glucose or food loading. Taking sitagliptin at a daily dose of 100 mg for 4-6 months significantly improved the function of pancreatic beta cells in patients with type 2 diabetes mellitus, as evidenced by corresponding changes in such markers as HOMA-β (assessment of homeostasis in the-β model), the proinsulin/insulin ratio, and assessment of the response of pancreatic beta cells according to the panel of repeated food tolerance tests. According to the data of phase II and III clinical trials, the effectiveness of glycemic control of sitagliptin in the 50 mg x 2 times daily regimen was comparable to the effectiveness of the 100 mg once daily regimen. The study examined the effect of sitagliptin in combination with metformin, either sitagliptin alone, metformin alone, or placebo on changes in plasma concentrations of active and total GLP-1 and glucose after meals in healthy volunteers. The weighted average concentrations of active GLP-1 increased approximately 2-fold 4 hours after ingestion after taking sitagliptin alone or metformin alone compared to placebo. The combined use of sitagliptin and metformin provided a summation of the effect with a 4-fold increase in the concentration of active GLP-1 compared to the dynamics in the placebo group. Taking sitagliptin alone was accompanied by an increase in the concentration of active GLP-1 alone due to inhibition of the DPP-4 enzyme, while taking metformin alone was accompanied by a symmetrical increase in the concentration of total and active GLP-1. The data obtained reflect different mechanisms underlying the increase in the concentration of active GLP-1 after taking these two drugs. The results of the study also demonstrated that it is sitagliptin, and not metformin, that provides an increase in the concentration of active GLP-1. In studies in healthy volunteers, sitagliptin intake was not accompanied by a decrease in glucose concentration and did not cause hypoglycemia, which confirms the glucose-dependent nature of the insulinotropic effect and suppression of glucagon synthesis. Effect on blood pressure in a study involving patients with arterial hypertension, concomitant use of antihypertensive drugs (one or more of the list: angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor antagonists, slow calcium channel blockers, beta-blockers, and diuretics) with sitagliptin were generally well tolerated by patients. In this category of patients, sitagliptin showed a slight antihypertensive effect: at a daily dose of 100 mg, sitagliptin reduced the average daily outpatient systolic blood pressure (BP) by 2 mm Hg compared to the placebo group. No antihypertensive effect was observed in patients with normal blood pressure. Effect on cardiac electrophysiology In a study in healthy volunteers, sitagliptin was taken once at a dose of 100 mg or 800 mg (8 times the recommended dose), or placebo. After taking the recommended therapeutic dose, no effect of the drug on the duration of the QT interval was observed either at the time of its maximum plasma concentration or at other points of verification throughout the study. After taking 800 mg, the maximum increase in the placebo-adjusted mean change in the duration of the QT interval compared to the baseline value 3 hours after taking the drug was 8.0 msec. Such a small increase was assessed as clinically insignificant. After taking an 800 mg dose, the maximum plasma concentration of sitagliptin was approximately 11 times higher than the corresponding value after taking a therapeutic dose of 100 mg. Pharmacokinetics: The results of a study to determine bioequivalence in healthy volunteers showed that the combined tablets metformin + sitagliptin 500 mg+50 mg and 1000 mg+50 mg are bioequivalent to separate use of the corresponding doses of sitagliptin and metformin. Taking into account the proven bioequivalence of tablets with the lowest and highest dose of metformin, tablets with an intermediate dose of metformin (metformin + sitagliptin) of 850 mg + 50 mg were also assigned bioequivalence, provided that fixed doses of drugs were combined in the tablet. Absorption of sitagliptinabsolute bioavailability of sitagliptin is approximately 87%. Taking sitagliptin concomitantly with fatty foods does not affect the pharmacokinetics of the drug. Metforminabsolute bioavailability of metformin when taken on an empty stomach at a dose of 500 mg is 50-60%. The results of studies of a single dose of metformin tablets in doses from 500 mg to 1500 mg and from 850 mg to 2550 mg indicate a violation of dose proportionality with increasing dose, which is more likely due to reduced absorption than accelerated elimination. Concomitant use of the drug with food reduces the rate and amount of absorbed metformin, which is confirmed by a decrease in the maximum plasma concentration Cmax by about 40%, a decrease in the area under the concentration-time curve AUC by about 25%, as well as a 35-minute delay in reaching the maximum plasma concentration Tmax after a single dose of metformin at a dose of 850 mg simultaneously with food compared to the values of the corresponding parameters after taking a similar dose of the drug on an empty stomach. The clinical significance of reducing the values of pharmacokinetic parameters has not been established. Distribution of sitagliptin The average volume of distribution at steady state after a single intravenous use of 100 mg of sitagliptin in healthy volunteers is approximately 198 liters.The fraction of sitagliptin reversibly binding to plasma proteins is relatively small (38%). Metformin volume of distribution of metformin after a single oral dose of 850 mg averaged 654±358 l. Metformin binds to plasma proteins only to a very small extent. Metformin is partially and temporarily distributed in red blood cells. When using metformin in the recommended doses and regimens, plasma concentrations of the equilibrium state (usually According to controlled studies, the maximum plasma concentrations of the drug did not exceed 5 micrograms/ml even after taking the maximum doses of the drug. Metabolismsitagliptin Approximately 79% of sitagliptin is excreted unchanged by the kidneys, the metabolic transformation of the drug is minimal. After oral use of 14C-labeled sitagliptin, approximately 16% of the administered radioactivity was excreted as sitagliptin metabolites. Trace concentrations of 6 sitagliptin metabolites were detected. These drugs do not contribute to the plasma DPP-4 inhibitory activity of sitagliptin. In vitro studies have identified cytochrome CYP3A4 and CYP2C8 isoenzymes as the main enzymes involved in limited sitagliptin metabolism. Metformin After a single intravenous injection of metformin to healthy volunteers, almost all of the administered dose was excreted unchanged by the kidneys. Metabolic transformations of the drug in the liver and its excretion with bile do not occur. Elimination of sitagliptin After ingestion of 14C-labeled sitagliptin by healthy volunteers, almost all the radioactivity administered was eliminated from the body within a week, including 13% through the intestines and 87% by the kidneys. The average oral half-life of sitagliptin 100 mg is approximately 12.4 hours, with a renal clearance of approximately 350 ml/min. Sitagliptin is excreted primarily by renal excretion through the mechanism of active tubular secretion. Sitagliptin is a substrate of the third type of human organic anion transporter (hOAT-3), which is involved in the process of elimination of sitagliptin by the kidneys. The clinical significance of hOAT-3 involvement in sitagliptin transport has not been established. P-glycoprotein may be involved in the renal elimination of sitagliptin (as a substrate), but the P-glycoprotein inhibitor cyclosporine does not reduce the renal clearance of sitagliptin. Metformin The renal clearance of metformin exceeds creatinine clearance by 3.5 times, indicating active renal secretion as the main route of elimination. After taking metformin, about 90% of the absorbed drug is excreted by the kidneys within the first 24 hours with a plasma half-life of approximately 6.2 hours, in the blood this value is extended to 17.6 hours, indicating the possible participation of red blood cells as a potential distribution compartment. Pharmacokinetics in selected patient groups Patients with type 2 diabetesitagliptinthe pharmacokinetics of sitagliptin in patients with type 2 diabetes mellitus are similar to those in healthy individuals. Metformin With preserved renal function, the pharmacokinetic parameters after single and repeated doses of metformin in patients with type 2 diabetes mellitus and healthy individuals are the same, no accumulation of the drug occurs when taking therapeutic doses. Patients with renal insufficiency Velmetiya® should not be prescribed to patients with renal insufficiency (see section “Contraindications”), Sitagliptin patients with moderate renal insufficiency showed an approximately 2-fold increase in the plasma AUC of sitagliptin, and in patients with severe and end-stage (on hemodialysis), the increase in AUC values was 4-fold compared to the control values in healthy individuals. In patients with reduced renal function (according to creatinine clearance), the half-life of the drug is prolonged, and renal clearance decreases in proportion to the decrease in creatinine clearance. Patients with hepatic insufficiency with sitagliptin in patients with moderate hepatic insufficiency (Child-Pugh score 7-9), the average AUC and Cmax of sitagliptin after a single 100 mg dose increase by approximately 21% and 13%, respectively, compared with healthy individuals. This difference is not clinically significant. There are no clinical data on the use of sitagliptin in patients with severe hepatic insufficiency (more than 9 points on the Child-Pugh scale). However, based on the predominantly renal route of elimination of the drug, significant changes in the pharmacokinetics of sitagliptin in patients with severe hepatic insufficiency are not predicted. Metformin Studies of the pharmacokinetic parameters of metformin in patients with hepatic insufficiency have not been conducted. Sex of sitagliptin According to the analysis of pharmacokinetic data from phase I and II clinical trials, gender did not have a clinically significant effect on the pharmacokinetic parameters of sitagliptin. Metformin pharmacokinetic parameters of metformin did not differ significantly between healthy individuals and patients with type 2 diabetes mellitus based on gender. According to controlled clinical trials, the hypoglycemic effects of metformin in men and women were similar. Elderly patients with sitagliptin According to a population pharmacokinetic analysis of data from phase I and II clinical trials, the age of patients did not have a clinically significant effect on the pharmacokinetic parameters of sitagliptin. The sitagliptin concentration in elderly patients (65-80 years) was approximately 19% higher than in young patients. Metformin-limited data from controlled pharmacokinetic studies of metformin in healthy elderly individuals suggest that the total plasma clearance of the drug decreases, the elimination half-life is prolonged, and the Cmax value increases compared to young healthy individuals. These data indicate that age-related changes in the pharmacokinetics of the drug are due to a decrease in excretory function of the kidneys. Treatment with Velmetiya® is not indicated in the elderly aged ≥80 years, except in persons whose creatinine clearance indicates that renal function is not reduced (see section ” Special instructions. Metformin”). No studies of metformin + sitagliptin in children have been conducted. Race of sitagliptin According to the analysis of pharmacokinetic data from phase I and II clinical trials, race did not have a clinically significant effect on the pharmacokinetic parameters of sitagliptin, including in representatives of the Caucasian and Mongoloid races, representatives of Latin American countries and other ethnic and racial groups. Metformin Studies on the potential effect of race on the pharmacokinetic parameters of metformin have not been conducted. According to controlled studies of metformin in patients with type 2 diabetes, the hypoglycemic effect of the drug was comparable in representatives of the Caucasian, Negroid races and Latin American countries. Body Mass Index (BMI)Sitagliptin According to complex and population-based analyses of pharmacokinetic parameters from phase I and II clinical trials, BMI did not have a clinically significant effect on the pharmacokinetic parameters of sitagliptin.

Indications

Monotherapy Velmetiya® is indicated as a starting therapy for patients with type 2 diabetes mellitus to improve glycemic control if diet and exercise regimen do not allow for adequate control. Velmetiya® is indicated as an adjunct to diet and exercise regimen to improve glycemic control in patients with type 2 diabetes mellitus who have not achieved adequate control during metformin or sitagliptin monotherapy, or after unsuccessful combined treatment with the two drugs. Combination therapy Velmetiya® is indicated in patients with type 2 diabetes mellitus to improve glycemic control in combination with sulfonylurea derivatives (triple combination: metformin + sitagliptin + a sulfonylurea derivative), when diet and exercise regimen in combination with two of these three drugs: metformin, sitagliptin or sulfonylurea derivatives do not lead to adequate glycemic control. Velmetiya® is indicated in patients with type 2 diabetes mellitus to improve glycemic control in combination with thiazolidinediones (PPARy receptor agonists activated by the peroxisome proliferator), when diet and exercise regimen in combination with two of these three drugs: metformin, sitagliptin or thiazolidinedione do not lead to adequate glycemic control. Velmetiya® is indicated in patients with type 2 diabetes mellitus to improve glycemic control in combination with insulin, when diet and exercise regimen in combination with insulin do not lead to adequate glycemic control.

Use during pregnancy and lactation

Velmetiya®There have been no adequately controlled studies of Velmetiya® or its components in pregnant women, therefore, there are no data on the safety of its use in pregnant women. Velmetiya®, like other oral hypoglycemic drugs, is not recommended for use during pregnancy. No experimental studies of the combined drug Velmetiya® have been conducted to assess its effect on reproductive function. Only available data from sitagliptin and metformin studies are provided.Sitagliptin Sitagliptin did not demonstrate teratogenicity during organogenesis when administered orally to rats at daily doses up to 250 mg / kg or rabbits at doses up to 125 mg / kg (which exceeds the plasma exposure of the drug in humans by 32 and 22 times, respectively, after taking the recommended daily therapeutic dose of 100 mg). There was a slight increase in the incidence of rib malformation in offspring (absence, hypoplasia, curvature) with oral use of the drug in daily doses of 1000 mg/kg (which exceeds the exposure in humans by about 100 times after taking the recommended daily dose of 100 mg). There was a slight decrease in body weight in both sexes of the offspring of rats during breastfeeding and a decrease in the rate of weight gain at the end of breastfeeding in males when the drug was administered orally to pregnant females at a daily dose of 1000 mg/kg. However, data from experimental reproductive studies do not always correlate directly with the effect of the drug on human reproductive function. Metformin Metformin did not demonstrate teratogenicity when administered orally to rats in daily doses up to 600 mg/kg. This exceeds the plasma exposure of the drug in humans by 2 and 6 times (in rats and rabbits, respectively) after taking the maximum recommended daily therapeutic dose of 2000 mg. The values of the plasma concentration of the drug in the fetus indicate partial placental transfer. Experimental studies to determine the penetration of the components of the combined drug Velmetiya® into breast milk have not been conducted. According to individual drug studies, both sitagliptin and metformin are excreted in rat breast milk. There are no data on the penetration of sitagliptin into human breast milk. Therefore, the drug Velmetiya® should not be prescribed during breastfeeding.

Contraindications

-Known hypersensitivity to sitagliptin, metformin or any of the components of Velmetiya®. – Type 1 diabetes mellitus. – Kidney disease or decreased renal function (with serum creatinine concentrations ≥1.5 mg / dl and ≥1.4 mg / dl in men and women, respectively, or decreased creatinine clearance (- Acute conditions with a risk of developing impaired renal function: – dehydration (with diarrhea, vomiting), fever, severe infectious diseases, – hypoxia (shock, sepsis, kidney infections, bronchopulmonary diseases). – Acute or chronic metabolic acidosis, including diabetic ketoacidosis (with or without coma). – Clinically expressed manifestations of acute and chronic diseases that can lead to the development of tissue hypoxia (including heart or respiratory failure, acute myocardial infarction). – Extensive surgical operations and injuries, when insulin therapy is indicated (see the section “Special instructions”). – Hepatic insufficiency, impaired liver function. – Chronic alcoholism, acute alcohol poisoning. – Pregnancy, breast-feeding period. – Lactic acidosis (including in the anamnesis). – Use for at least 48 hours before and within 48 hours after conducting radioisotope or X-ray studies with the introduction of an iodine-containing contrast agent (see the section “Interaction with other drugs”). – Compliance with a hypocaloric diet (less than 1000 kcal / day). – Children under 18 years of age. With caution:Use in the elderly of Almetiya®Since the main route of elimination of sitagliptin and metformin is through the kidneys and since renal excretory function decreases with age, precautions for prescribing Velmetiya® increase in proportion to age. Elderly patients should be carefully selected for dosage and regularly monitored for renal function (see section ” Special instructions. Monitoring of renal function”). Sitagliptin According to clinical studies, the efficacy and safety of sitagliptin in elderly (>65 years) patients was comparable with the efficacy and safety in young (>Metformin The number of elderly patients among participants in controlled trials of metformin was insufficient to make a formal conclusion about age-related differences in the effectiveness and safety of the drug, although no such differences were observed according to available data. Since metformin is mainly excreted by the kidneys and when their function is impaired, the likelihood of adverse reactions increases, the drug should only be prescribed to patients with confirmed normal renal function (see the section “Contraindications”).

Side effects

In studies, combined treatment with sitagliptin and metformin was generally well tolerated in patients with type 2 diabetes mellitus. The frequency of side effects associated with sitagliptin and metformin combined treatment was comparable to that of metformin in combination with placebo. Combination treatment with sitagliptin and metforminomstarting therapy In a study of initial combination therapy with sitagliptin and metformin (sitagliptin 50 mg + metformin 500 mg or 1000 mg x 2 times a day) in the combination therapy group compared to the monotherapy groups with metformin (500 mg or 1000 mg x 2 times a day), sitagliptin (100 mg 1 time a day) or placebo, the following drug – related adverse reactions were observed, observed with a frequency of ≥1% in the combination treatment group and more often than in the placebo group: diarrhea (sitagliptin + metformin – 3.5%, metformin – 3.3%, sitagliptin – 0.0%, placebo-1.1%), nausea (1.6%,2.5%,0.0% and 0.6%), dyspepsia (1.3%,1.1%,0.0% and 0.0%), flatulence (1.3%,0.5%,0.0% and 0.0%), vomiting (1.1%,0.3%,0.0% and 0.0%), headache (1.3%,1.1%,0.6% and 0.0%) and hypoglycemia (1.1%,0.5%,0.6% and 0.0%). Adding sitagliptin to current metformin therapy In the study, when adding sitagliptin at a dose of 100 mg / day to current metformin treatment, the only adverse reaction associated with the drug and observed with a frequency of ≥1% in the sitagliptin treatment group and more often than in the placebo group was nausea (sitagliptin + metformin – 1.1%, placebo + metformin – 0.4%). Hypoglycemia and gastrointestinal adverse reactions In sitagliptin-metformin combination studies, the incidence of hypoglycemia (regardless of causation) in the combination therapy groups was comparable to that in the metformin-placebo treatment groups (1.3-1.6% and 2.1%, respectively). The frequency of monitored gastrointestinal adverse reactions (regardless of causation) in the sitagliptin and metformin combination treatment groups was comparable to the frequency in the metformin monotherapy groups: diarrhea (sitagliptin + metformin – 7.5%, metformin-7.7%), nausea (4.8%,5.5%), vomiting (2.1%,0.5%), abdominal pain (3.0%,3.8%). In all studies, adverse reactions in the form of hypoglycemia were recorded based on all reports of clinically significant symptoms of hypoglycemia; no additional measurement of blood glucose concentration was required. Combined treatment with sitagliptin, metformin and a sulfonylurea derivative In a study using sitagliptin at a dose of 100 mg/day against the background of current combined treatment with glimepiride at a dose of ≥4 mg/day and metformin at a dose of ≥1500 mg/day, the following drug – related adverse reactions were observed with a frequency of ≥1% in the sitagliptin treatment group and more often than in the placebo group: hypoglycemia (sitagliptin – 13.8%, placebo-0.9%), constipation (1.7% and 0.0%). Combined treatment with sitagliptin, metformin and an fparyagonist According to a study using sitagliptin at a dose of 100 mg/day against the background of current combined treatment with rosiglitazone and metformin at week 18 of treatment, the following drug – related adverse reactions were observed with a frequency of ≥1% in the sitagliptin treatment group more often than in the placebo group: 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 week 54 of combination treatment, the following drug – related adverse reactions were observed with a frequency of ≥1% in the sitagliptin treatment group and more often than in the placebo group: headache (sitagliptin – 2.4%, placebo-0.0%), hypoglycemia (2.4%,0.0%), upper respiratory tract infections (1.8%,0.0%), nausea (1.2%,1.1%), cough (1.2%,0.0%), fungal skin infections (1.2% 0.0%), peripheral edema (1.2%,0.0%), vomiting (1.2%,0.0%). Combined treatment with sitagliptin, metformin and insulin In a study using sitagliptin at a dose of 100 mg/day against the background of current combined treatment with metformin at a dose of ≥1500 mg/day and a constant dose of insulin, the only adverse reaction associated with taking the drug and observed with a frequency of ≥1% in the sitagliptin treatment group and more often than in the placebo group was hypoglycemia (sitagliptin – 10.9%, placebo – 5.2%). In another study in which patients received sitagliptin as an adjunct to insulin therapy (with or without metformin), the only adverse reaction observed with a frequency of ≥1% in the sitagliptin and metformin treatment group, and more often than in the placebo and metformin group, was vomiting (sitagliptin and metformin-1.1%, placebo and metformin-0.4%). Pancreatitis in a generalized analysis of studies on the use of sitagliptin (at a dose of 100 mg / day) or the corresponding 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 also the sitagliptin Cardiovascular Safety Assessment Study (TECOS) below (see section ” Special Instructions.Pancreatitis”). No clinically significant abnormalities in vital signs or ECG parameters (including the duration of the QTc interval) were observed during combination therapy with sitagliptin and metformin. Adverse reactions due to the use of sitagliptin In patients, there were no adverse reactions due to the use of sitagliptin, the frequency of which was ≥1%. Adverse reactions due to the use of metformin, adverse reactions observed in the metformin group in >5% of patients and more often than in the placebo group are diarrhea, nausea/vomiting, flatulence, asthenia, dyspepsia, abdominal discomfort and headache. Sitagliptin Cardiovascular Safety Assessment Study (TECOS)The sitagliptin Cardiovascular Safety Assessment Study (TECOS) included 7332 patients who took sitagliptin and 7339 patients who took placebo in the general population of patients who were prescribed treatment. The study drug (sitagliptin or placebo) was added to standard therapy in accordance with existing national standards for the selection of the target level of HbA 1C and the control of cardiovascular risk factors. A total of 2004 patients aged 75 years and older were included in the study. Overall incidence of serious adverse events in patients treated with sitagliptin. It was the same as in patients taking placebo. Evaluation of previously designated diabetes-related complications revealed a comparable incidence of adverse events between the groups, including infections (18.4% in sitagliptin-treated patients and 17.7% in placebo-treated patients) and impaired renal function (1.4% in sitagliptin-treated patients and 1.5% in placebo-treated patients). The adverse event profile in patients aged 75 years and older was generally similar to that in the general population. In the “intention-to-treat” patient population, among those who initially received insulin therapy and/or sulfonylureas, the incidence of severe hypoglycemia was 2.7% in patients taking sitagliptin and 2.5% in patients taking placebo. Among patients who did not initially receive insulin and/or sulfonylureas, the incidence of severe hypoglycemia was 1.0% in patients taking sitagliptin and 0.7% in patients taking placebo. The incidence of confirmed pancreatitis was 0.3% in patients treated with sitagliptin and 0.2% in patients treated with placebo. The incidence of confirmed malignancies was 3.7% in patients treated with sitagliptin and 4.0% in patients treated with placebo. Post-marketing observationsin the course of post-marketing monitoring of the use of the combination of metformin + sitagliptin or sitagliptin included in its composition, in monotherapy and/or in combination therapy with other hypoglycemic agents, additional adverse events were identified. Since these data were obtained voluntarily from a population of indeterminate size, the frequency and causal relationship of these adverse events with therapy cannot be determined. These include: hypersensitivity reactions, including anaphylaxis; angioedema; skin rash; urticaria; cutaneous vasculitis; exfoliative skin diseases, including Stevens-Johnson syndrome; acute pancreatitis, including hemorrhagic and necrotic forms with or without fatal outcome; deterioration of renal function, including acute renal failure (sometimes requiring dialysis); upper respiratory tract infections; nasopharyngitis; constipation; vomiting; headache; arthralgia; myalgia; limb pain; back pain; pruritus; pemphigoid. Changes in sitagliptin laboratory parameters The frequency of laboratory deviations in the sitagliptin and metformin treatment groups was comparable to the frequency in the placebo and metformin treatment groups. In most, but not all, clinical trials, there was a slight increase in the white blood cell count (approximately 200/µl compared to placebo, the average content at the beginning of treatment is 6600/µl) due to an increase in the number of neutrophils. This change is not considered clinically significant. Metformin In metformin studies, a decrease in the normal concentration of cyanocobalamin (vitamin B12) to subnormal values in the blood serum was observed in approximately 7% of patients, without clinical manifestations. Such a decrease, due to selective malabsorption of vitamin B12 (namely, a violation of the formation of a complex with the internal Castle factor necessary for the absorption of vitamin B12), very rarely leads to the development of anemia and is easily corrected by the withdrawal of metformin or an additional intake of vitamin B12 (see the section ” Special instructions. Metformin”).

Interaction

Sitagliptin and metformin Simultaneous use of multiple doses of sitagliptin (50 mg twice daily) and metformin (1000 mg twice daily) was not accompanied by significant changes in the pharmacokinetic parameters of sitagliptin or metformin in patients with type 2 diabetes mellitus. Studies of the inter-drug effect on the pharmacokinetic parameters of Velmetiya® have not been conducted, but a sufficient number of similar studies have been conducted for each of the components of the drug, sitagliptin and metformin. Sitagliptin In studies on 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 the CYP isoenzymes of the cytochrome CYP3A4,2C8 or 2C9 system. In vitro data indicate that sitagliptin also does not inhibit the isoenzymes CYP2D6,1A2,2C19 and 2B6 and does not induce CYP3A4. According to a population pharmacokinetic analysis of patients with type 2 diabetes mellitus, 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 hypocholesterolemic drugs (statins, fibrates, ezetimibe), antiplatelet agents (clopidogrel), antihypertensive drugs (ACE inhibitors, angiotensin II receptor antagonists, beta-blockers, slow calcium channel blockers, hydrochlorothiazide), analgesics, and nonsteroidal anti-inflammatory drugs anti-depressants (naproxen, diclofenac, celecoxib), antidepressants (bupropion, fluoxetine, sertraline), antihistamines (cetirizine), proton pump inhibitors (omeprazole, lansoprazole) and drugs for the treatment of erectile dysfunction (sildenafil). There was an increase in the AUC (11%), as well as the average Cmax (18%) of digoxin when co-administered with sitagliptin. This increase is not considered clinically significant, but patient monitoring is recommended when digoxin is co-administered. The AUC and Cmax of sitagliptin increased by 29% and 68%, respectively, with a single oral dose of sitagliptin 100 mg and cyclosporine (a potent P-glycoprotein inhibitor) 600 mg. These changes in the pharmacokinetic parameters of sitagliptin are not clinically significant. Metformingliburide: No changes in the pharmacokinetic and pharmacodynamic parameters of metformin were observed in the drug – drug interaction study of single doses of metformin and glyburide in patients with type 2 diabetes mellitus. Changes in glyburide AUC and Cmax values were highly variable. Insufficient information (single dose) and the discrepancy between the plasma concentration of glyburide and the observed pharmacodynamic effects call into question the clinical significance of this interaction. Furosemide: in a drug-to-drug interaction study of single doses of metformin and furosemide in healthy volunteers, changes in the pharmacokinetic parameters of both drugs were observed. Furosemide increased the Cmax concentration of metformin in plasma and whole blood by 22%, the AUC value of metformin in whole blood by 15%, without changing the renal clearance of the drug. The Cmax and AUC values of furosemide, in turn, decreased by 31% and 12%, respectively, and the elimination half-life decreased by 32% without significant changes in the renal clearance of furosemide. There is no information about the inter-drug interaction of the two drugs during long-term joint use. Nifedipine: a study of the drug-drug interaction between nifedipine and metformin after a single dose of drugs in healthy volunteers revealed an increase in plasma Cmax and AUC of metformin by 20% and 9%, respectively, as well as an increase in the amount of metformin excreted by the kidneys. Tmax and the half-life of metformin did not change. It is based on increased absorption of metformin in the presence of nifedipine. The effect of metformin on the pharmacokinetics of nifedipine is minimal. Cationic drugs: cationic drugs (i. e., amiloride, digoxin, morphine, procainamide, quinidine, quinine, ranitidine, triamterene, trimethoprim, or vancomycin) released by tubular secretion can theoretically interact with metformin, competing for a shared renal tubular transport system. Similar competition was observed when metformin and cimetidine were co-administered to healthy volunteers in single-and multiple-dose studies, with a 60% increase in the Cmax of metformin in plasma and whole blood and a 40% increase in the AUC of metformin in plasma and whole blood. In the single-dose study, the half-life of metformin did not change. Metformin did not affect the pharmacokinetics of cimetidine.Although these drug-drug interactions are mostly theoretical (with the exception of cimetidine), careful monitoring of the patient and dose adjustment of Velmetia® and/or the above-mentioned cationic drugs excreted by the proximal renal tubules are recommended in cases of simultaneous use. Others: Some medications have hyperglycemic potential and may interfere with established glycemic control. These include thiazide and other diuretics, glucocorticosteroids, phenothiazines, thyroid medications, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, slow calcium channel blockers, and isoniazid. When prescribing these drugs to a patient receiving Velmetiya®, careful monitoring of the parameters of glycemic control is recommended. No changes in the pharmacokinetic parameters of these drugs were observed when metformin and propranolol or metformin and ibuprofen were administered simultaneously to healthy volunteers. Only a small proportion of metformin binds to plasma proteins, therefore, inter-drug interactions of metformin with drugs that actively bind to plasma proteins (salicylates, sulfonamides, chloramphenicol and probenecid) are unlikely, unlike sulfonylurea derivatives, which also actively bind to plasma proteins.

How to take, course of use and dosage

General Information The dosage regimen of Velmetiya® should be selected individually, based on current therapy, efficacy and tolerability, but not exceeding the maximum recommended daily dose of sitagliptin 100 mg. The drug Velmetiya® is usually prescribed 2 times a day with meals, with a gradual increase in the dose in order to minimize possible side effects from the gastrointestinal tract (GI), characteristic of metformin. Dosage recommendations The initial dose of Velmetiya ® depends on the current hypoglycemic therapy. The drug Velmetiya® is taken 2 times a day with meals. The following dosages of the drug are offered:850 mg of metformin + 50 mg of sitagliptin,1000 mg of metformin + 50 mg of sitagliptin. Starting therapy In patients with type 2 diabetes mellitus with inadequate glycemic control while following a diet and exercise regimen, the recommended starting dose is 500 mg of metformin + 50 mg of sitagliptin * 2 times a day. Subsequently, the dose can be increased to 1000 mg of metformin + 50 mg of sitagliptin 2 times a day. For patients who do not achieve adequate control on metformin monotherapy, the recommended starting dose of Velmetiya® for patients who do not achieve adequate control on metformin monotherapy should provide the recommended therapeutic daily dose of sitagliptin 100 mg, i. e. 50 mg of sitagliptin 2 times a day plus the current dose of metformin. For patients who do not achieve adequate control on sitagliptin monotherapy, the recommended starting dose for patients who do not achieve adequate control on sitagliptin monotherapy is 500 mg of metformin + 50 mg of sitagliptin* 2 times a day. In the future, the dose can be increased to 1000 mg of metformin + 50 mg of sitagliptin 2 times a day. Patients taking the adjusted dose of sitagliptin due to renal insufficiency should not be treated with Velmetiya® (see section “Contraindications”). For patients taking a combination of sitagliptin and Metformin, when switching from combined treatment with sitagliptin and metformin, the starting dose of Velmetiya® may be equivalent to the doses taken separately with sitagliptin and metformin. For patients taking two of these three hypoglycemic medications – sitagliptin, metformin, or sulfonylurea derivatives-the starting dose of Velmetiya® should provide the recommended therapeutic daily dose of sitagliptin 100 mg, i. e. 50 mg of sitagliptin 2 times a day. The starting dose of metformin is determined based on the level of glycemic control and the current (if the patient is taking this drug) dose of metformin. Increasing the dose of metformin should be gradual to minimize the associated gastrointestinal side effects. For patients taking a sulfonylurea derivative, it is advisable to reduce the current dose to reduce the risk of sulfonyl-induced hypoglycemia (see section “Special instructions”). For patients taking two of these three hypoglycemic medications – sitagliptin, metformin, or PPARy receptor agonists (thiazolidinediones)The starting dose of Velmetiya® should correspond to the daily dose of sitagliptin 100 mg, i. e. 50 mg of sitagliptin 2 times a day and the previously taken dose of metformin. If it is necessary to increase the dose of metformin, gradual titration of the drug is recommended to avoid gastrointestinal side effects. For patients taking two of these three hypoglycemic medications – sitagliptin, metformin or insulin-the starting dose of Velmetiya® should correspond to the daily dose of sitagliptin 100 mg, i. e. 50 mg of sitagliptin 2 times a day and the previously taken dose of metformin. If it is necessary to increase the dose of metformin, gradual titration of the drug is recommended to avoid gastrointestinal side effects. Patients may need to reduce the dose of insulin to prevent the risk of hypoglycemia (see section “Special instructions”). No specific studies have been conducted to assess the safety and effectiveness of switching from treatment with other hypoglycemic drugs to treatment with the combined drug Velmetiya. Any changes in the treatment of type 2 diabetes should be carried out with caution and under the control of appropriate parameters, taking into account possible changes in glycemic control. Use in children The safety of Velmetiya® in children and adolescents under 18 years of age has not been studied. * – when prescribing initial therapy, it should be borne in mind that the drug Velmetiya® in a dosage of 500 mg of metformin + 50 mg of sitagliptin is not registered in the Russian Federation.

Overdose

Sitagliptin During clinical trials in healthy volunteers, a single dose of sitagliptin up to 800 mg was generally well tolerated. Minimal changes in the QT interval, which are not considered clinically significant, were observed in one of the studies of sitagliptin at a daily dose of 800 mg (see the section “Pharmacodynamics. Influence on the electrophysiology of the heart”). A dose of more than 800 mg per day in humans has not been studied. In clinical studies of repeated use of the drug (phase I), no adverse reactions associated with sitagliptin treatment were observed when taking the drug in a daily dose of up to 400 mg for 28 days. In case of overdose, it is necessary to start standard maintenance measures: removal of the drug that has not yet been absorbed from the gastrointestinal tract, monitoring of vital signs, including an ECG, and prescribing symptomatic therapy if necessary. Sitagliptin is poorly dialyzed: according to clinical studies, only 13.5% of the dose was eliminated during a 3 – to 4-hour dialysis session. If clinically necessary, prolonged hemodialysis is prescribed. There are no data on the effectiveness of sitagliptin peritoneal dialysis. Metformin There have been cases of metformin overdose, including ingestion in amounts exceeding 50 g (50,000 mg). Hypoglycemia was observed in approximately 10% of all overdose cases, but a clear association with metformin overdose was not established. Lactic acidosis was associated with approximately 32% of all metformin overdose cases (see section ” Special instructions. Metformin”). Emergency hemodialysis is possible (metformin is dialyzed at a rate of up to 170 ml / min in conditions of good hemodynamics) to accelerate the elimination of excess metformin in case of suspected overdose.

Special instructions

Velmetiya®Acute pancreatitis, including hemorrhagic or necrotic pancreatitis with or without a fatal outcome, has been reported in patients taking sitagliptin (see section “Side effects”). Patients should be informed about the characteristic symptoms of acute pancreatitis: persistent, severe abdominal pain. Clinical manifestations of pancreatitis disappeared after discontinuation of sitagliptin. If pancreatitis is suspected, you should stop taking Velmetiya® and other potentially dangerous medications. Monitoring of renal function The primary route of elimination of metformin and sitagliptin is renal excretion. The risk of metformin accumulation and lactic acidosis increases in proportion to the degree of impaired renal function, so Velmetiya® should not be prescribed to patients with serum creatinine concentrations above the upper age limit of normal. In elderly patients, due to age-related decline in renal function, adequate glycemic control should be sought at the minimum dose of Velmetiya®. In elderly patients, especially over the age of 80 years, regular monitoring of renal function is carried out. Before starting treatment with metformin +sitagliptin, as well as at least once a year after starting treatment, proper tests confirm normal renal function. If there is an increased likelihood of developing renal dysfunction, renal function monitoring is carried out more often, and if it is detected, Velmetiya® is discontinued. The development of hypoglycemia when used concomitantly with sulfonylurea derivatives or insulin, as in the case of taking other hypoglycemic agents, hypoglycemia was observed with the simultaneous use of sitagliptin and metformin in combination with insulin or sulfonylurea derivatives (see the section “Side effects”). To reduce the risk of developing sulfonyl-induced or insulin-induced hypoglycemia, the dose of a sulfonylurea or insulin derivative should be reduced (seesection “Dosage and use”). Sitagliptin Development of hypoglycemia when used concomitantly with sulfonylurea derivatives or insulin in clinical studies of sitagliptin, both in monotherapy and in combination with drugs that do not lead to hypoglycemia (i. e., metformin or PPARy agonists – thiazolidinediones), the incidence of hypoglycemia in the group of patients taking sitagliptin was close to the frequency in the group of patients taking placebo. As with other hypoglycemic agents, hypoglycemia was observed when sitagliptin was co-administered in combination with insulin or sulfonylureas (see section “Side effects”). To reduce the risk of developing sulfonyl-induced or insulin-induced hypoglycemia, the dose of a sulfonylurea or insulin derivative should be reduced (see the section “Dosage and use”). Hypersensitivity reactsin the course of post-marketing monitoring of the use of the combination of metformin + sitagliptin or sitagliptin, which is part of it, in monotherapy and/or in combination therapy with other hypoglycemic agents, hypersensitivity reactions were detected. These reactions included anaphylaxis, angioedema, and exfoliative skin disorders, including Stevens-Johnson syndrome. Since these data were obtained voluntarily from a population of indeterminate size, the frequency and causal relationship with therapy; these adverse reactions cannot be determined. These reactions occurred within the first 3 months after starting treatment with sitagliptin, some were observed after taking the first dose of the drug. If a hypersensitivity reaction is suspected, you should stop taking Velmetiya®, evaluate other possible causes of the adverse event, and prescribe another lipid-lowering therapy (see the sections “Contraindications” and ” Side effects. Post-registration observations”). Metformin Lactic acidosis Lactic acidosis is a rare but serious metabolic complication that develops due to the accumulation of metformin during treatment with metformin + sitagliptin. Lethality in lactic acidosis reaches approximately 50%. The development of lactic acidosis can also occur against the background of certain somatic diseases, in particular, diabetes mellitus or any other pathological condition accompanied by severe hypoperfusion and hypoxemia of tissues and organs. Lactic acidosis is characterized by an increased concentration of lactate in blood plasma (>5 mmol / l), a low blood pH, electrolyte disturbances with an increase in the anion interval, and an increase in the lactate/pyruvate ratio. If metformin is the cause of acidosis, its plasma concentration is usually >5 micrograms / ml. Lactic acidosis was reported to be very rare during metformin treatment (approximately 0.03 cases per 1000 patient-years, with a mortality rate of approximately 0.015 cases per 1000 patient-years). During the 20,000 patient-years of metformin treatment, no cases of lactic acidosis have been reported in clinical trials. Known cases have occurred primarily in patients with diabetes mellitus with severe renal insufficiency, including severe renal pathology and renal hypoperfusion, often in combination with concomitant multiple somatic/surgical diseases and polypragmasia. Significantly increased risk of lactic acidosis in patients with chronic heart failure requiring significant medication correction, especially in unstable angina/chronic heart failure in the acute stage, accompanied by severe hypoperfusion and hypoxemia. The risk of developing lactic acidosis increases in proportion to the degree of impaired renal function and the patient’s age, so adequate monitoring of renal function, as well as the use of the minimum effective dose of metformin, can significantly reduce the risk of developing lactic acidosis. Careful monitoring of renal function is especially necessary in the treatment of elderly patients, and in patients over 80 years of age, metformin treatment is initiated only after confirmation of adequate renal function by evaluating creatinine clearance, since these patients are more at risk of developing lactic acidosis. In addition, metformin should be discontinued immediately for any condition associated with hypoxemia, dehydration, or sepsis. Given that lactate excretion is significantly reduced in patients with impaired liver function, metformin should not be prescribed to patients with clinical or laboratory signs of liver disease. Alcohol intake should be restricted during metformin treatment, as alcohol potentiates the effect of metformin on lactate metabolism. In addition, metformin treatment is temporarily discontinued for the duration of intravascular radiopaque studies and surgical interventions. The onset of lactic acidosis is often difficult to detect, and it is accompanied only by non-specific symptoms, such as malaise, myalgia, respiratory distress syndrome, increased drowsiness, and non-specific dyspeptic symptoms. As lactic acidosis worsens, hypothermia, hypotension, and resistant bradyarrhythmia may also occur. The doctor and patient should be aware of the possible significance of such symptoms, and the patient should immediately inform the doctor of their occurrence. Treatment with metformin is canceled until the situation is clarified. Determine the plasma concentrations of electrolytes, ketones, blood glucose, as well as (according to indications) the pH value of the blood, the concentration of lactate. Sometimes information about the plasma concentration of metformin may also be useful. After the patient gets used to the optimal dose of metformin, the gastrointestinal symptoms characteristic of the initial stages of treatment should disappear. If such symptoms appear, they are most likely a signal of developing lactic acidosis or other serious illness. If during treatment with metformin, the concentration of lactate in venous blood plasma exceeds the upper limit of normal, remaining no higher than 5 mmol/l, this is not pathognomonic for lactic acidosis and may be due to conditions such as poorly controlled diabetes mellitus or obesity, or excessive physical exertion, or technical measurement error. Any patient with diabetes mellitus and metabolic acidosis who does not have evidence of ketoacidosis (ketonuria and ketonemia) is at risk of developing lactic acidosis. Lactic acidosis is a condition that requires emergency care in a medical facility. Treatment with metformin is canceled and the necessary maintenance therapy measures are immediately carried out. Since metformin is dialyzed at a rate of up to 170 ml / min under good hemodynamic conditions, immediate hemodialysis is recommended for rapid correction of acidosis and elimination of accumulated metformin. These measures often lead to the rapid disappearance of all symptoms of lactic acidosis and the restoration of the patient’s condition (see the section “Contraindications”). Hypoglycemia Under normal conditions, with metformin monotherapy, hypoglycemia does not develop, but its development is possible against the background of fasting, after significant physical exertion without subsequent compensation for calories consumed, while taking other hypoglycemic drugs (sulfonylureas and insulin derivatives) or alcohol. Elderly, debilitated or emaciated patients, patients who abuse alcohol, patients with adrenal or pituitary insufficiency are more likely to develop hypoglycemia. Hypoglycemia is difficult to recognize in elderly patients and patients taking beta-blockers. Concomitant therapy: Concomitant pharmacotherapy may negatively affect renal function or metformin distribution. Concomitant use of drugs that negatively affect renal function, hemodynamics, or metformin distribution (such as cationic drugs that are eliminated from the body by tubular secretion) should be prescribed with caution (see the section “Interaction with other drugs. Metformin”). Radiological studies with intravascular use of iodine-containing contrast agents (for example, intravenous urogram, intravenous cholangiography, angiography, computed tomography with intravenous use of contrast agents)Intravascular use of iodine-containing contrast agents has been associated with lactic acidosis in metformin-treated patients and may cause acute renal failure (see section “Contraindications”). Therefore, patients who are scheduled for such a study should temporarily stop taking Velmetiya® 48 hours before and within 48 hours after the study. Resumption of treatment is acceptable only after laboratory confirmation of normal renal function. Hypoxic statesvascular collapse (shock) of any etiology, acute heart failure, acute myocardial infarction and other conditions accompanied by the development of hypoxemia can provoke the development of lactic acidosis and pre-renal azotemia. If these conditions develop in a patient during treatment with metformin + sitagliptin, the drug should be discontinued immediately. Surgical interventionsthe use of Velmetiya® should be discontinued for the duration of any surgical intervention (with the exception of small manipulations that do not require restrictions on drinking and hunger) and up to the resumption of normal food intake, provided laboratory confirmation of normal renal function. Alcohol consumption Alcohol potentiates the effect of metformin on lactic acid metabolism. The patient should be warned about the risk of alcohol abuse (single intake of large amounts or constant intake of small doses) during treatment with metformin + sitagliptin.Impaired liver function Since lactic acidosis has been reported in patients with impaired liver function, it is not recommended to prescribe Velmetiya® to patients with clinical or laboratory signs of liver disease. Plasma cyanocobalamin (vitamin B12) concentration In metformin studies,7% of patients showed a decrease in the initially normal plasma concentration of cyanocobalamin (vitamin B12) without developing clinical symptoms of deficiency. Such a decrease may be due to selective malabsorption of vitamin B12 (namely, a violation of the formation of a complex with the internal Castle factor necessary for the absorption of vitamin B12), very rarely leads to the development of anemia and is easily corrected by the withdrawal of metformin or an additional intake of vitamin B12. When treated with metformin + sitagliptin, it is recommended to check the hematological parameters of the blood annually, and any deviations that occur should be studied and corrected. Patients predisposed to developing vitamin B12 deficiency (due to reduced intake or absorption of vitamin B12 or calcium) are recommended to determine the plasma concentration of vitamin B12 at intervals of 2-3 years. Changes in the clinical status of patients with adequately controlled type 2 diabetes mellitus If laboratory abnormalities or clinical symptoms of the disease (especially any condition that cannot be clearly identified) occur in a patient with previously adequately controlled type 2 diabetes mellitus during treatment with metformin + sitagliptin, ketoacidosis or lactic acidosis should be immediately excluded. Assessment of the patient’s condition should include blood tests for electrolytes and ketones, blood glucose concentration, as well as (if indicated) blood pH, plasma concentrations of lactate, pyruvate and metformin. If acidosis of any etiology develops, you should immediately stop taking Velmetiya® and take appropriate measures to correct acidosis. Loss of glycemic control In situations of physiological stress (hyperthermia, trauma, infection, or surgery), a patient with previously stable glycemic control may temporarily lose glycemic control. During such periods, it is acceptable to temporarily replace the drug Velmetiya® with insulin therapy, and after the acute situation is resolved, the patient can resume the previous treatment. Sitagliptin Cardiovascular Safety Assessment Study (TECOS)In the sitagliptin Cardiovascular Safety Assessment Study (TECOS), patients received sitagliptin or placebo, which were added to standard therapy in accordance with existing national standards for determining target HbA1c levels and controlling cardiovascular risk factors. At the end of the median follow-up period of 3 years, in patients with type 2 diabetes mellitus, taking sitagliptin in addition to standard treatment did not increase the risk of serious cardiovascular adverse events or the risk of hospitalization for heart failure, compared with standard treatment without additional sitagliptin. Influence on the ability to drive vehicles and mechanisms:No studies have been conducted to study the effect of Velmetiya® on the ability to drive vehicles and work with mechanisms. However, cases of dizziness and drowsiness reported with sitagliptin should be considered. In addition, patients should be aware of the risk of hypoglycemia when Velmetiya® is co-administered with sulfonylureas or insulin.

Form of production

Film-coated tablets

Storage conditions

Store at a temperature not exceeding 25 °C. Keep out of reach of children.

Shelf

life is 2 years.

Active ingredient

Metformin, Sitagliptin

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

For adults as directed by your doctor

Indications

Type 2 Diabetes