Composition, form of production and packaging
Tablets covered with a filmy coating of light yellow with a faint pinkish hue of color, oval, with oblique margins; on one side marking "NVR", on the other - "LLO".
1 tab.
vildagliptin 50 mg
metformin hydrochloride 500 mg
Excipients: giprolose - 49.5 mg, magnesium stearate - 6.5 mg, hypromellose - 12.858 mg, titanium dioxide (E171) - 2.36 mg, macroline 4000 - 1.283 mg, talc - 1.283 mg, iron oxide yellow (E172) - 0.21 mg.
6 pcs. - blisters (1, 3, 5, 6, 12, 18, 36) - packs of cardboard.
10 pieces. - blisters (1, 3, 5, 6, 12, 18, 36) - packs of cardboard.
The tablets covered with a film membrane of yellow with a weak grayish shade of color, oval, with oblique margins; on one side marking "NVR", on the other - "SEH".
1 tab.
vildagliptin 50 mg
metformin hydrochloride 850 mg
Auxiliary substances: giprolose - 84.15 mg, magnesium stearate - 9.85 mg, hypromellose - 18.58 mg, titanium dioxide (E171) - 2.9 mg, macroline 4000 - 1.86 mg, talc - 1.86 mg, iron oxide yellow (E172) - 0.82 mg.
6 pcs. - blisters (1, 3, 5, 6, 12, 18, 36) - packs of cardboard.
10 pieces. - blisters (1, 3, 5, 6, 12, 18, 36) - packs of cardboard.
The tablets covered with a film membrane of dark yellow with a grayish shade of color, oval with oblique margins; on one side marking "NVR", on the other - "FLO".
1 tab.
vildagliptin 50 mg
metformin hydrochloride 1000 mg
Auxiliary substances: giprolose - 99 mg, magnesium stearate - 11 mg, hypromellose - 20 mg, titanium dioxide (E171) - 2.2 mg, macrogol 4000 - 2 mg, talc - 2 mg, iron oxide yellow (E172) - 1.8 mg.
6 pcs. - blisters (1, 3, 5, 6, 12, 18, 36) - packs of cardboard.
10 pieces. - blisters (1, 3, 5, 6, 12, 18, 36) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2016.
PHARMACHOLOGIC EFFECT
Pharmacodynamics
The composition Galvus Met consists of two hypoglycemic agents with different mechanisms of action: vildagliptin, belonging to the class of inhibitors of dipeptidyl peptidase-4 (DPP-4), and metformin (in the form of hydrochloride), a representative of the biguanide class. The combination of these components makes it possible to more effectively control the concentration of blood glucose in patients with type 2 diabetes mellitus within 24 hours.
Vildagliptin, a representative of the class of stimulants of the islet apparatus of the pancreas, selectively inhibits the DPP-4 enzyme that destroys the type 1 glucagon-like peptide (GLP-1) and the glucose-dependent insulinotropic polypeptide (GIP). Metformin reduces the production of glucose by the liver, reduces the absorption of glucose in the intestine and reduces insulin resistance by enhancing the capture and utilization of glucose by peripheral tissues.
Metformin induces intracellular synthesis of glycogen, acting on glycogen synthetase, and enhances the transport of glucose by some gluculin-transport membrane proteins (GLUT-1 and GLUT-4).
Vildagliptin
Rapid and complete inhibition of DPP-4 activity after taking vildagliptin causes both basal and stimulated food intake of GLP-1 secretion and GIP from the intestine to the systemic circulation throughout the day.
Increasing the concentration of GLP-1 and HIP, vildagliptin causes an increase in the sensitivity of ОІ-cells of the pancreas to glucose, which leads to an improvement in the glucose-dependent secretion of insulin. The degree of improvement in the function of the ОІ-cells depends on the degree of their initial damage, so in individuals without diabetes mellitus (with a normal glucose concentration in the blood plasma), vildagliptin does not stimulate insulin secretion and does not decrease the glucose concentration.
Increasing the concentration of endogenous GLP-1, vildagliptin increases the sensitivity of ОІ-cells to glucose, which leads to an improvement in glucose-dependent regulation of glucagon secretion. Reducing the increased concentration of glucagon after meals, in turn, causes a decrease in insulin resistance.
The increase in the ratio of insulin / glucagon to the background of hyperglycemia, caused by an increase in the concentration of GLP-1 and GUI, causes a decrease in the production of glucose by the liver both during and after meals, which leads to a decrease in the concentration of glucose in the blood plasma.
In addition, vildagliptin has been associated with a decrease in plasma lipid concentrations after ingestion, but this effect is not related to its effect on GLP-1 or GIP and to the improvement of pancreatic islet cell function. It is known that an increase in the concentration of GLP-1 can lead to a slowdown in gastric emptying, however, against the background of the use of vildagliptin, this effect is not observed.
When using vildagliptin in 5759 patients with type 2 diabetes for 52 weeks, a significant long-term decrease in the concentration of glycated hemoglobin (HbA1c) and fasting blood glucose was noted in monotherapy or in combination with metformin, sulfonylurea, thiazolidinedione, or insulin for 52 weeks.
Metformin
Metformin improves glucose tolerance in patients with type 2 diabetes, reducing the concentration of glucose in the plasma both before and after meals.
Unlike sulfonylurea derivatives, metformin does not cause hypoglycemia in either patients with type 2 diabetes, nor in healthy individuals (except in special cases).The drug therapy does not lead to the development of hyperinsulinemia. When metformin is used, the secretion of insulin does not change, while the concentration of insulin in the blood plasma on an empty stomach and during the day can decrease.
When metformin is used, there is a favorable effect on the metabolism of lipoproteins: a decrease in the concentration of total cholesterol, low density lipoprotein cholesterol and triglycerides, not related to the effect of the drug on the concentration of glucose in the blood plasma.
Vildagliptin + metformin
When using combination therapy with vildagliptin and metformin at daily doses of 1500-3000 mg of metformin and 50 mg of vildagliptin 2 times / day for 1 year, a statistically significant persistent decrease in blood glucose (determined by decreasing HbA1c) and an increase in the proportion of patients in whom the decrease The concentration of HbA1c was not less than 0.6-0.7% (compared with the group of patients who continued to receive only metformin).
In patients who received a combination of vildagliptin and metformin, there was no statistically significant change in body weight compared with the baseline.Twenty-four weeks after the start of treatment, a decrease in systolic and diastolic BP in patients with arterial hypertension was noted in the groups treated with vildagliptin in combination with metformin.
When a combination of vildagliptin and metformin was used as an initial therapy for patients with type 2 diabetes mellitus, a dose-dependent decrease in HbA1c values ​​was observed for 24 weeks compared to monotherapy with these drugs. The incidence of hypoglycemia was minimal in both treatment groups.
With the use of vildagliptin (50 mg 2 times / day) simultaneously with / without metformin in combination with insulin (mean dose 41 units), the HbA1c statistically significantly decreased in patients in the clinical study by 0.72% (initial, average 8.8%). The incidence of hypoglycemia in patients treated was comparable to the incidence of hypoglycemia in the placebo group.
When using vildagliptin (50 mg 2 times / day) concomitantly with metformin (> 1500 mg) in combination with glimepiride (> 4 mg per day), the HbA1c statistically significantly decreased by 0.76% (from an average of 8.8%) in patients in the clinical study .
PHARMACOKINETICS
Vildagliptin
Suction
When administered on an empty stomach, vildagliptin is rapidly absorbed, and its maximum concentration in the blood plasma (C max ) is reached after 1.75 hours after administration. With simultaneous intake with food, the absorption rate of vildagliptin decreases only slightly: a decrease in Cmax by 19% and an increase in the time to reach 2.5 hours. However, the intake of food does not affect the degree of absorption and the area under the concentration-time curve (AUC).
Vildagliptin is rapidly absorbed, and its absolute bioavailability after oral administration is 85%. C max and AUC in the therapeutic range of doses increase approximately in proportion to the dose.
Distribution
The degree of binding of vildagliptin to plasma proteins is low (9.3%). The drug is distributed evenly between the plasma and erythrocytes. The distribution of vildagliptin is presumably extravascular, the volume of distribution in the equilibrium state after intravenous administration (Vss) is 71 liters.
Metabolism
Biotransformation is the main way of removing vildagliptin. In the human body, a 69% dose of the drug is converted. The main metabolite - LAY151 (57% of the dose) is pharmacologically inactive and is a product of hydrolysis of the cyano component. About 4% of the dose of the drug is subjected to amide hydrolysis.
In experimental studies, there is a positive effect of DPP-4 on the hydrolysis of the drug. Vildagliptin is not metabolized with the participation of cytochrome P450 isoenzymes. According to in vitro studies, vildagliptin is not a substrate of P (CYP) 450 isoenzymes, does not inhibit or induce isoenzymes of the cytochrome CYP450 system.
Excretion
After ingestion, about 85% of the dose is excreted by the kidneys and 15% through the intestine, while renal excretion of unchanged vildagliptin is 23%. With IV introduction, the average half-life of T 1/2 reaches 2 h, the total plasma clearance and renal clearance of vildagliptin are 41 l / h and 13 l / h, respectively. T 1/2 after oral administration is about 3 hours regardless of the dose.
Pharmacokinetics in special cases
Sex, body mass index and ethnicity do not affect the pharmacokinetics of vildagliptin.
Patients with impaired hepatic function
In patients with impaired liver function of mild and moderate severity (6-10 points according to the Child-Pugh classification) after a single application of the drug, a decrease in the bioavailability of vildagliptin by 8% and 20%, respectively. In patients with severe hepatic dysfunction (Child-Pugh grade 12), the bioavailability of vildagliptin is increased by 22%. The maximum change in the bioavailability of vildagliptin, an increase or decrease on average to 30%, is not clinically significant.Correlations between the degree of severity of violations of the liver and the bioavailability of the drug is not revealed.
Patients with impaired renal function
In patients with impaired renal function of mild, moderate or severe AUC, vildagliptin increased in comparison with healthy volunteers by 1.4, 1.7 and 2 times, respectively. AUC of the metabolite LAY151 increased in 1.6, 3.2, and 7.3 times, and the metabolite BQS867 - in 1.4, 2.7, and 7.3 times in patients with impaired renal function of mild, moderate and severe, respectively. Limited data in patients with terminal stage of chronic kidney disease (CKD) indicate that the indicators of this group are similar to those in patients with impaired renal function of severe severity. The concentration of metabolite LAY151 in patients with terminal CKD increased by 2-3 times compared with the concentration in patients with impaired renal function of severe degree. Excretion of type-glyptin in hemodialysis is limited (3% for a procedure lasting more than 3-4 hours 4 hours after a single dose of the drug).
Use in patients aged? 65 years old
The maximum increase in bioavailability of the drug by 32% (an increase of C max by 18%) in patients older than 70 years is not clinically significant and does not affect the inhibition of DPP-4.
Use in patients under the age of 18 years
Pharmacokinetic features of vildagliptin in children and adolescents under the age of 18 years have not been established.
Metformin
Suction
Absolute bioavailability of metformin for oral administration at a dose of 500 mg on an empty stomach was 50-60%. The maximum concentration in plasma (C max ) is reached after 1.81-2.69 h after administration. With an increase in the dose from 500 mg to 1500 mg, or at doses of 850 mg to 2250 mg orally, there was a slower increase in pharmacokinetic parameters (than would be expected for linear dependence). This effect is caused not so much by the change in the excretion of the drug, as by the slowing of its absorption. Against the background of food intake, the degree and rate of absorption of metformin also decreased somewhat. Thus, with a single dose of 850 mg together with food, a decrease of C max and AUC was observed by approximately 40% and 25% and an increase in the time to reach a maximum concentration (T max ) of 35 min. The clinical significance of these facts is not established.
Distribution
With a single oral dose of 850 mg, the apparent volume of metformin distribution is 654 В± 358 liters. The preparation practically does not bind to plasma proteins, while sulfonylureas compounds bind to them more than 90%. Metformin penetrates into erythrocytes (probably the amplification of this process with time). When metformin is used according to the standard scheme (standard dose and frequency of administration), the equilibrium concentration of the drug in the blood plasma is reached within 24-48 hours and, as a rule, does not exceed 1 Ојg / ml.
During controlled clinical trials, C max metformin in blood plasma did not exceed 5 Ојg / ml (even when taken in high doses).
Metabolism
With a single intravenous administration of metformin to healthy volunteers, it is excreted by the kidneys unchanged. In this case, the drug is not metabolized in the liver (the person does not have any metabolites) and is not excreted with bile.
Excretion
Since the renal clearance of metformin is approximately 3.5 times greater than the creatinine clearance (CC), the main way of excretion is tubular secretion. If ingested, approximately 90% of the absorbed dose is excreted by the kidneys within the first 24 hours; while T 1/2 of the blood plasma is about 6.2 hours. T 1/2metformin from whole blood is about 17.6 hours, which indicates the accumulation of a significant part of the drug in erythrocytes.
Pharmacokinetics in special cases
The sex of patients does not affect the pharmacokinetics of metformin.
Patients with impaired hepatic function
Patients with hepatic insufficiency did not study the pharmacokinetic features of metformin.
Patients with impaired renal function
In patients with impaired renal function (assessed by CC), T 1/2 metformin from plasma and whole blood increases, and its renal clearance decreases in proportion to the decrease in CK.
Use in patients aged? 65 years old
According to limited pharmacokinetic data, a decrease in the total plasma clearance of metformin and an increase in T 1/2 and C max were observed in healthy people aged ≥65 years compared with young adults. These features of the pharmacokinetics of metformin in people over 65 years are probably primarily associated with a change in kidney function, and therefore in patients over 80 years of age, the use of Galvus Met is possible only with normal QC.
Use in patients under the age of 18 years
Pharmacokinetic features of metformin in children and adolescents under the age of 18 years have not been established.
Use in patients of different ethnicity
There is no evidence of the influence of ethnicity of patients on the pharmacokinetic features of metformin.
In controlled clinical studies of metformin in patients with type 2 diabetes of different ethnicity, the hypoglycemic effect of the drug was manifested to the same extent.
Vildagliptin + metformin
The studies show bioequivalence in AUC and C max of the Galvus Met preparation in three different dosages (50 mg + 500 mg, 50 mg + 850 mg and 50 mg + 1000 mg) and vildagliptin and metformin taken in appropriate doses as separate tablets.
The intake of food does not affect the extent and rate of absorption of vildagliptin in the composition Galvus Met. Values ​​of Cmax and AUC metformin in the composition Galvus Met with simultaneous intake with food decreased by 26% and 7%, respectively. In addition, against the background of food intake, metformin absorption was slowed, which led to an increase in T max (from 2.0 to 4.0 h). A similar change in Cmax and AUC on the background of food intake was noted in the case of metformin use, but in the latter case the changes were less significant. The effect of food on the pharmacokinetics of vildagliptin and metformin in the composition Galvus Met did not differ from that for both drugs alone.
INDICATIONS
Diabetes mellitus type 2 (in combination with diet and exercise):
- with insufficient effectiveness of monotherapy with vildagliptin or metformin;
- in patients who previously received combination therapy with vildagliptin and metformin in the form of monopreparations;
- in combination with sulfonylurea derivatives (triple combination therapy) in patients previously treated with sulfonylureas and metformin without adequate glycemic control;
- in triple combination therapy with insulin in patients who received a stable dose of insulin therapy and metformin without achieving adequate glycemic control;
- as an initial therapy in patients with type 2 diabetes mellitus with insufficient effectiveness of diet therapy, physical exercises and the need to improve the control of glycemia.
DOSING MODE
The drug is used inside. Dosage regimen Galvus Met must be selected individually, depending on the effectiveness and tolerability of therapy. When using Galvus Met, do not exceed the recommended maximum daily dose of vildagliptin (100 mg).
The recommended initial dose of the drug Galvus Met should be selected, taking into account the duration of diabetes mellitus and blood glucose levels, the patient and existing patient circuit vildagliptin treatment and / or metformin. To reduce the severity of side effects from the gastrointestinal tract, characteristic of metformin, the drug Galvus Met taken during meals.
Starting dose Galvus Met monotherapy after failure of vildagliptin
Treatment with Galvus Met can begin with a dosage of one tablet of 50 mg + 500 mg 2 times a day; after evaluation of the therapeutic effect of the dose can be gradually increased.
Starting dose Galvus Met metformin monotherapy after failure
Depending on the dose already received metformin, treatment with Galvus Met can begin with a dosage of one tablet of 50 mg + 500 mg, 50 mg or 850 mg + 50 mg + 1000 mg of 2 times / day.
Starting dose Galvus Met in patients previously treated with a combination therapy of vildagliptin and metformin in the form of separate tablets
, depending on the doses already taken vildagliptin or metformin, treatment with Galvus Met should start with the tablets as close dosage to the existing treatment, 50 mg + 500 mg, 50 mg or 850 mg + 50 mg + 1000 mg, and the dose adjusted, depending on the efficiency.
The starting dose of the drug Galvus Met as initial therapy in patients with type 2 diabetes mellitus with inadequate efficiency of diet therapy and exercise
As initial therapy, the drug Galvus Met should be used in an initial dose of 50 mg + 500 mg 1 time / day, and after evaluating the therapeutic effect of gradually increasing the dose to 50 mg + 1000 mg of 2 times / day.
Combination therapy with Galvus Met and sulfonylureas or insulin
Dose Galvus MW calculated from the dose of vildagliptin 50 mg x 2 times / day (100 mg daily) and metformin dose of previously received in the form of monotherapy.
Patients with impaired renal function
in patients with impaired renal function may require adjustment of the dose when creatinine clearance (QC calculated by Cockcroft-Gault) in the range from 60 to 90 ml / min. Use of the drug Galvus Met patients with creatinine clearance <60 mL / min contraindicated.
Use in patients under the age? 65
Metformin is excreted by the kidneys. As in patients over 65 years of age is often marked renal impairment, the dose of the drug Galvus Met in these patients should be adjusted based on renal function. In applying the drug in patients older than 65 years should regularly monitor kidney function.
Use in patients under 18 years
since safety and efficacy of Galvus Met drug in children and adolescents under 18 years have not been studied, the use of the drug is contraindicated in these patients.
SIDE EFFECT
The following data relate to the use of vildagliptin and metformin as monotherapy or in combination.
The therapy of vildagliptin were observed rarely hepatic dysfunction (including hepatitis) asymptomatic. In most cases, these disorders and abnormalities in liver function of normal resolved spontaneously without complications after the cessation of drug therapy. In the application of vildagliptin 50 mg 1 or 2 times / day rate increasing activity "liver" enzymes ALT or AST in 3 times the upper limit of normal (ULN) was 0.2% or 0.3%, respectively (compared to 0.2% in the control group) . Increased activity of "liver" enzymes in most cases were asymptomatic, did not progress and was not associated with cholestasis or jaundice.
The following criteria were used to evaluate the incidence of adverse events (AEs): very common (> 1/10), common (> 1/100, <1/10), uncommon (> 1/1000, <1/100), rarely ( > 1/10 000, <1/1000), very rare (<1/10 000), including isolated cases.
Adverse reactions, probably involving the use of combination therapy of vildagliptin and metformin (at which the incidence of vildagliptin and metformin different from that during treatment with placebo and metformin more than 2%) are presented below.
Disorders of the nervous system: often - headache, dizziness, tremor. In the application of vildagliptin in combination with metformin in different dosages of hypoglycemia was observed in 0.9% of cases (for comparison with placebo plus metformin - 0.4%).
FrequencyAEs from the gastrointestinal tract in the combined therapy of vildagliptin and metformin was 12.9%. When metformin similar AEs occurred in 18.1% of patients.
In the groups of patients treated with metformin in combination with vildagliptin, disorders of the gastrointestinal tract were observed with a frequency of 10-15%, and in patients treated with metformin in combination with placebo, - with a frequency of 18%. Long-term clinical studies of up to 2 years did not show any additional safety profile deviation or unforeseen risks with vildagliptin monotherapy application.
Studying application of the combination vildagliptin and metformin as a starting therapy for type 2 diabetes showed no risks and additional data on safety of use.
In applying vildagliptin simultaneously with insulin
In controlled clinical trials at application vildagliptin at a dose of 50 mg of 2 times / day in combination with insulin in combination with metformin or without frequency discontinuation due to development of adverse reactions was 0.3% in the vildagliptin group, with it was not in the placebo group of cases treatment discontinuation.
Hypoglycemia rate was comparable in both groups (14.0% in the group of vildagliptin and 16.4% in the placebo group). In the group of vildagliptin were cases of severe hypoglycemia in two patients in the placebo group - in 6 patients.
At the time of completion of the study vildagliptin no effect on the average body weight (body weight increased by 0.6 kg as compared with the original in the vildagliptin group, were observed in the placebo group changes).
AEs in patients treated with vildagliptin 50 mg of 2 times / day in combination with insulin (with or without metformin it) are shown below.
Disorders of the nervous system: often - headache.
Disorders of the gastrointestinal tract : often - nausea, gastroesophageal reflux disease; rarely - diarrhea, flatulence.
Violations by the Metabolism and nutrition: often - hypoglycemia.
General disorders and the site of injection: often - chills.
In the application of vildagliptin in combination with sulfonylurea
cases of drug withdrawal associated with the development of adverse events in the combination therapy group vildagliptin, metformin and glimepiride, it was noted. In the placebo group, combination therapy of metformin and glimepiride incidence of AEs was 0.6%.
Hypoglycemia is often observed in both groups (5.1% in the combination therapy of vildagliptin, glimepiride and metformin and 1.9% in the placebo group, combination therapy with metformin and glimepiride). In the vildagliptin group recorded an episode of severe hypoglycemia.
At the time of completion of the study no significant effect on body weight was not detected (+0.6 kg group vildagliptin and -0.1 kg in the placebo group).
AEs in patients treated with vildagliptin 50 mg of 1 or 2 times a day in combination with sulfonylureas, presented below (with or without metformin).
Infectious and parasitic diseases: very rarely - nasopharyngitis.
Disorders of the nervous system: often - dizziness, tremor, asthenia.
Disorders of the gastrointestinal tract: rarely - constipation.
Violations by the Metabolism and nutrition: often - hypoglycemia.
Violations of the skin and subcutaneous tissue disorders: often - hyperhidrosis.
In applying vildagliptin monotherapy
Infectious and parasitic diseases : very rarely - upper respiratory tract infection, nasopharyngitis.
Disorders of the nervous system : often - dizziness; seldom - a headache.
Disorders of the gastrointestinal tract: rarely - constipation.
Violations of the skin and subcutaneous tissue disorders: rare - skin rash.
Violations by musculoskeletal and connective tissue disorders : often - arthralgia.
Violations by vessels: rarely - peripheral edema.
When applying the combination vildagliptin and metformin therapy were noted clinically significant increase in the frequency above AEs noted when receiving vildagliptin.
Monotherapy vildagliptin, metformin or incidence of hypoglycemia was 0.4% (infrequently).
Monotherapy and combination therapy vildagliptin vildagliptin + metformin did not affect the body weight of the patients.
Long-term clinical studies of up to 2 years did not show any additional safety profile deviation or unforeseen risks with vildagliptin monotherapy application.
postmarketing studies
In the post-registration period revealed the following side reactions (since the data are reported in voluntarily from a population of uncertain size and reliably determine the frequency of these adverse events is not possible, in connection with which they are classified as the frequency is unknown): hepatitis (invertible upon termination of therapy), the increase in "liver" enzymes, myalgia, rash, pancreatitis, bullous and exfoliative skin lesions, arthralgia, in rare cases severe.
When metformin monotherapy
Violations by metabolism and nutrition: very often - loss of appetite; very rarely - lactic acidosis.
Disorders of the gastrointestinal tract: often - bloating, nausea, vomiting, diarrhea, abdominal pain; often - dysgeusia.
Violations of the liver and biliary tract: very rarely - hepatitis.
Disorders of the skin and subcutaneous tissue disorders: very rarely - skin reactions (including erythema, pruritus, urticaria).
Laboratory and instrumental data: very rare - decrease absorption of vitamin B 12 , a change in liver function.
Reducing absorption of vitamin B 12 and its reduction in serum concentrations during treatment with metformin is very rarely observed in patients treated with the drug for a long time and are usually presented no clinical significance. Consideration should be given an opportunity to reduce the intake of vitamin B 12 in patients with megaloblastic anemia.
Isolated cases of hepatitis, which have been observed during treatment with metformin were resolved after its cancellation.
It is necessary to warn the patient or his relatives that the deterioration of the clinical course of any of these side effects in the instructions or the appearance of any other side effects not mentioned in the instructions, you should inform your doctor.
CONTRAINDICATIONS
- increased sensitivity of vildagliptin or metformin or in any other components of the formulation;
- Renal failure or renal dysfunction (creatinine at serum concentrations> 1.5 mg% (> 135 pmol / L) for men and> 1.4 mg% (> 110 pmol / L) for women);
- acute conditions, with the risk of renal dysfunction: dehydration (diarrhea, vomiting), fever, severe infectious disease, condition, hypoxia (shock, sepsis, kidney infection, bronchopulmonary diseases);
- acute and chronic heart failure, acute myocardial infarction, acute heart failure (shock), respiratory insufficiency;
- impaired liver function;
- acute or chronic metabolic acidosis (including diabetic ketoacidosis in combination with or without coma). Diabetic ketoacidosis should be adjusted insulin therapy. Lactic acidosis (including history);
- preparation should not be used for 48 hours before surgery, radioisotope, radiological studies with administration of contrast agents and for 48 hours after their performance;
- Pregnancy and lactation;
- type 1 diabetes;
- chronic alcoholism, acute alcohol poisoning;
- compliance with the low-calorie diets (less than 1000 kcal / day);
- the effectiveness and safety of the drug in children under 18 years of age has not been established;
- as in patients with impaired liver function in some instances lactic acidosis was noted, perhaps, one of the side effects of metformin, the drug Galvus Met should not be used in patients with liver disease or impaired liver function.
With caution: preparations containing metformin is recommended to be used with caution in patients older than 60 years when performing heavy physical work, due to an increased risk of developing lactic acidosis.
PREGNANCY AND LACTATION
Pregnancy
In experimental studies in animals when used vildagliptin at doses 200 times higher than recommended, the drug did not cause disturbances of the early development of the embryo and is not teratogenic. In the application of vildagliptin in combination with metformin 1:10 also did not reveal teratogenicity.
Because insufficient data on the drug administration Galvus Met pregnancy no use is contraindicated drug during pregnancy.
Breast-feeding
Metformin passes into breast milk. It is not known whether vildagliptin is excreted in breast milk. Use of the drug Galvus Met during breast-feeding is contraindicated.
APPLICATION FOR FUNCTIONS OF THE LIVER
Contraindications: renal insufficiency or renal dysfunction: the level of serum creatinine> 1.5 mg% (> 135 pmol / L) for men and> 1.4 mg% (> 110 pmol / L) for women; and acute conditions occurring at risk for renal dysfunction: dehydration (diarrhea, vomiting), fever, severe infectious disease, condition, hypoxia (shock, sepsis, infection pochechenye, bronchopulmonary diseases
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Contraindications: liver function abnormalities.
Since in patients with impaired liver function was observed in some cases lactic acidosis, which is one of the possible side effects of metformin, Galvus Met should not be used in patients with liver disease or impaired hepatic biochemical parameters
APPLICATION FOR CHILDREN
Contraindications: Children under 18 years of age (efficacy and safety have not been established).
APPLICATION IN ELDERLY PATIENTS
With caution is recommended to use preparations containing metformin, in patients older than 60 years.
SPECIAL INSTRUCTIONS
In patients receiving insulin treatment, drug Galvus Met is no substitute for insulin.
Vildagliptin
Abnormal liver function
Since the application vildagliptin increased activity of aminotransferases (usually without clinical manifestations) observed more often than in the control group, before application of the drug Galvus Met and regularly during drug treatment is recommended to determine liver function. In identifying the increase of activity of transaminases should conduct follow-up study to confirm the results and thereafter to conduct regular measurements of biochemical parameters of liver function until their normalization. If excess of AST or ALT yl 3
