Composition, form of production and packaging
Tablets from white to light yellow color, round, smooth, with bevelled edges; on one side of the overprint "NVR", on the other - "FB".
1 tab.
vildagliptin 50 mg
Excipients: microcrystalline cellulose - 95.68 mg, anhydrous - 47.82 mg, sodium carboxymethyl starch - 4 mg, magnesium stearate - 2.5 mg.
7 pcs. - blisters (2) - packs of cardboard.
7 pcs. - blisters (4) - packs of cardboard.
7 pcs. - blisters (8) - packs of cardboard.
7 pcs. - blisters (12) - packs of cardboard.
14 pcs. - blisters (2) - packs of cardboard.
14 pcs. - blisters (4) - packs of cardboard.
14 pcs. - blisters (8) - packs of cardboard.
14 pcs. - blisters (12) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2016.
PHARMACHOLOGIC EFFECT
Mechanism of action
Vildagliptin is a representative of the class of stimulators of the islet apparatus of the pancreas, selectively inhibits the enzyme dipeptidyl peptidase-4 (DPP-4). Rapid and complete inhibition of DPP-4 activity (> 90%) causes both a basal and food-stimulated secretion of glucagon-like peptide type 1 (GLP-1) and a glucose-dependent insulinotropic polypeptide (GIP) from the intestine to enter the systemic blood stream 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 glucose-dependent insulin secretion.
Pharmacodynamics
When using vildagliptin in a dose of 50-100 mg / day in patients with type 2 diabetes mellitus (type 2 diabetes), there is an improvement in the function of ОІ-cells of the pancreas. The degree of improvement in the function of the ОІ-cells depends on the degree of their initial damage; so in people without diabetes (with a normal concentration of glucose in the blood plasma), vildagliptin does not stimulate insulin secretion and does not reduce the concentration of glucose. 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 during 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 HIP, causes a decrease in glucose production by the liver both during and after meals, which leads to a decrease in the concentration of glucose in the blood plasma.
In addition, against the background of the use of vildagliptin there is a decrease in the concentration of lipids in the blood plasma after ingestion, but this effect is not associated with its effect on GLP-1 or GIP and improvement in the function of islet cells of the pancreas.
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 5795 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.
Using a combination of vildagliptin and metformin as an initial therapy in patients with type 2 diabetes mellitus, a dose-dependent decrease in HbA1c concentration was observed for 24 weeks compared to monotherapy with these drugs. The incidence of hypoglycemia was minimal in both treatment groups.
When vildagliptin is used at a dose of 50 mg once a day for 6 months in patients with type 2 diabetes with impaired renal function (GFR> 30, <50 ml / min / 1.73 m 2) or severe (GFR <30 ml / min / 1.73 m 2 ), a clinically significant decrease in HbA1c concentration was observed compared with placebo.
When using vildagliptin 50 mg twice daily in combination with / without metformin and insulin (average dose 41 units / day), a decrease in HbA1c of 0.77% from the original mean of 8.8% was observed with a statistically significant difference from placebo of 0.72%. The incidence of hypoglycemia in the vildagliptin group is comparable to that in the placebo group. When using vildagliptin 50 mg twice daily in combination with metformin (> 1500 mg / day) and glimepiride (> 4 mg / day), a statistically significant decrease in HbA1c was observed at 0.76% of the original mean of 8.8%.
PHARMACOKINETICS
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 rate of absorption of vildagliptin decreases slightly: a decrease in C max by 19% and an increase in the time to reach 2.5 hours. However, eating 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%). Vildagliptin is distributed evenly between blood plasma and erythrocytes. The distribution of vildagliptin occurs, presumably, extravascularly, the volume of distribution in the equilibrium state after intravenous administration (Vss) is 71 liters.
Metabolism
The main way to remove vildagliptin is biotransformation. In the human body, 69% of the dose of the drug undergoes biotransformation. 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 pre-clinical studies, there is a positive effect of DPP-4 on the hydrolysis of vildagliptin. Vildagliptin is metabolized without the participation of cytochrome P450 isoenzymes. Vildagliptin is not a substrate of P450 isoenzymes (CYP), does not inhibit or induce cytochrome P450 isoenzymes.
Excretion
After taking the drug inside about 85% of the dose is excreted by the kidneys and 15% by the intestine. Renal excretion of unchanged vildagliptin is 23%. With IV introduction, the mean half-life (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 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 (6-9 points on the Child-Pugh scale) after a single application of the drug, a decrease in the bioavailability of vildagliptin by 20% and 8%, respectively. In patients with severe hepatic dysfunction (10-12 points on the Child-Pugh scale), the bioavailability of vildagliptin is increased by 22%. Increasing or decreasing the maximum bioavailability of vildagliptin, not exceeding 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 degrees, respectively. Limited data in patients with terminal stage of chronic kidney disease (CKD) indicate that the parameters 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 stage CKD increased by 2-3 times compared with the concentration in patients with impaired renal function of severe degree.
When using the drug in patients with impaired renal function, dose adjustment may be required.
Excretion of vildagliptin in hemodialysis is limited (4 hours after a single dose of 3% with a duration of the procedure more than 3-4 hours).
Use in patients aged ≥65 years
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 aged 18 years
Pharmacokinetic features of vildagliptin in children and adolescents under the age of 18 years have not been established.
INDICATIONS
Diabetes mellitus type 2 (in combination with diet and exercise):
- as a monotherapy in the case of ineffectiveness of diet and exercise in patients with a contraindication to the use of metformin or in the case of ineffectiveness of metformin;
- in combination with metformin as an initial drug therapy with insufficient effectiveness of diet and exercise;
- as part of a two-component combination therapy with metformin, sulfonylureas, thiazolidinedione or insulin in the case of ineffectiveness of diet therapy, exercise and monotherapy of these drugs;
- as part of triple combination therapy: in combination with sulfonylurea derivatives and metformin, in patients previously treated with sulfonylureas and metformin derivatives against a background of diet and exercise and who did not achieve adequate glycemic control;
- as part of triple combination therapy: in combination with insulin and metformin, in patients who previously received insulin and metformin against a background of diet and exercise and who did not achieve adequate glycemic control.
DOSING MODE
The dose of Galvus should be selected individually depending on the effectiveness and tolerability.
The recommended dose of Galvus 50 mg 1 or 2 times / day. The maximum daily dose of the drug is 100 mg.
A dose of 50 mg / day should be taken 1 time a day in the morning, a dose of 100 mg / day should be divided into 2 divided doses - 50 mg in the morning and in the evening. If you miss a drug, you should take the missed dose as soon as possible. It should avoid taking a double dose in one day.
The drug Galvus is taken orally regardless of food intake.
The recommended dose of the drug in monotherapy or as part of a combination therapy with metformin, thiazolidinedione or insulin (in combination with metformin or without metformin) is 50 mg or 100 mg per day.
The recommended dose of Galvus as a part of a double combination therapy with sulfonylureas is 50 mg 1 time / day in the morning. In this population of patients, the effectiveness of the Galvus preparation at a dose of 100 mg / day was similar to that of a dose of 50 mg / day.
The recommended dose of Galvus in the combination therapy (vildagliptin + sulfonylurea derivatives + metformin ) is 100 mg / day.
If the goals of glycemic control are not achieved against the maximum daily dose of 100 mg, consider the possibility of adding other hypoglycemic drugs such as metformin, sulfonylureas, thiazolidinedione or insulin to Galvus.
Patients with impaired renal function
In patients with mild renal dysfunction (GFR> 60 ml / min / 1.73 m 2 ) and an average degree with GFR of 50-60 ml / min / 1.73 m 2, there is no need to correct the dosage regimen of the drug. In patients with impaired renal function of middle degree with GFR 30-50 ml / min / 1.73 m 2 and severe (GFR <30 ml / min / 1.73 m 2 ), including the terminal stage of CKD in patients on hemodialysis or passing procedure of hemodialysis, the drug should be used in a dose of 50 mg 1 time / day.
Patients in the age of? 65 years old
Older patients do not need a correction for dosing regimen Galvus.
Patients in the age of? 18 years
Since there is no experience of using Galvus in children and adolescents under the age of 18, it is not recommended to use the drug in patients of this category.
SIDE EFFECT
When using Galvus in monotherapy or in combination with other drugs, most of the adverse reactions were mild, temporary and did not require the withdrawal of therapy. Correlations between the incidence of adverse events (AEs) and age, gender, ethnicity, duration of administration, or dosing regimen were not identified.
The incidence of angioedema in the Galvus therapy was> 1/10000, <1/1000 (gradation was "rare") and was similar to that in the control group. Most cases of angioedema have been observed with the use of the drug in combination with ACE inhibitors. In most cases, angioedema was of moderate severity and was resolved independently during the continuation of vildagliptin therapy.
Against the background of therapy with Galvus, there was rarely a violation of liver function (including hepatitis) of the asymptomatic course. In most cases, these abnormalities and abnormalities of liver function parameters from the norm were resolved independently without complications after discontinuation of therapy with the drug. When using Galvus in a dose of 50 mg 1 or 2 times a day, the frequency of increase in activity of "hepatic" enzymes (ALT or AST> 3x HGV) was 0.2% or 0.3%, respectively (compared with 0.2% in the control group). The increase in activity of "liver" enzymes in most cases was asymptomatic, did not progress and was not accompanied by cholestasis or jaundice.
AEs are grouped according to the classification of organs and systems of MedDRA organs. Within each group of organ organs and organ systems, AEs are listed in order of decreasing incidence. Within each group, the incidence of AH is indicated in order of decreasing severity.
To assess the incidence of adverse events, the following criteria were used: very often (> 1/10), often (> 1/100, <1/10), infrequently (> 1/1 000, <1/100), rarely (> 1 / 10 000, <1/1 000), very rarely (<1/10 000), individual messages (the frequency is unknown).
When using Galvus in monotherapy
With the use of Galvus in a dose of 50 mg 1 or 2 times / day, the frequency of cancellation of therapy due to the development of unwanted reactions (0.2% or 0.1%, respectively) was no higher than in the placebo group (0.6%) or reference drug (0.5%).
Against the backdrop of monotherapy with Galvus at a dose of 50 mg 1 or 2 times / day, the incidence of hypoglycemia without increasing the severity of the condition was 0.5% (2 patients out of 409) and 0.3% (4 of 1082), respectively, comparable to the comparator and placebo 0.2%).
Infectious and parasitic diseases: very rarely - infections of the upper respiratory tract, nasopharyngitis.
Disturbances from the nervous system: often - dizziness; infrequently - a headache.
Disorders from the gastrointestinal tract : infrequently - constipation.
Violations from the vessels: infrequently - peripheral edema.
Long-term clinical trials of up to 2 years did not reveal any additional deviations in the safety profile or unforeseen risks when using vildagliptin in monotherapy.
When using Galvus in a dose of 50 mg 1 or 2 times / day in combination with metformin
With the use of Galvus in a dose of 50 mg / day in combination with metformin, the frequency of discontinuation of therapy due to the development of adverse reactions was 0.4% (in groups of vildagliptin (50 mg 2 times / day) + metformin and placebo + metformin cases of discontinuation of therapy due to development of undesirable reactions was not noted).
When using Galvus in a dose of 50 mg 1 or 2 times / day in combination with metformin, hypoglycemia was noted in 0.9% and 0.5% of cases, respectively (in the placebo + metformin group - 0.4%). In the group of the Galvus drug, there was no development of severe hypoglycemia.
Combined therapy of vildagliptin + metformin did not affect the body weight of patients.
Disturbances from the nervous system: often - tremor, dizziness, headache.
Disorders from the gastrointestinal tract: often - nausea.
Long-term clinical trials of up to 2 years did not reveal any additional deviations in the safety profile or unforeseen risks when using vildagliptin in combination with metformin.
The study of the use of combination vildagliptin and metformin as starting therapy for type 2 diabetes did not reveal any deviations in the safety profile or unforeseen risks.
When using Galvus in a dose of 50 mg / day in combination with sulfonylurea derivatives
With the use of Galvus in a dose of 50 mg / day in combination with glimepiride, the frequency of discontinuation of therapy due to the development of adverse reactions was 0.6% (compared to 0% in the glimepiride + placebo group).
The incidence of hypoglycemia in patients treated with Galvus at a dose of 50 mg / day with glimepiride was 1.2% (compared with 0.6% in the placebo + glimepiride group). In the group of the Galvus drug, there was no development of severe hypoglycemia.
When using Galvus in the recommended dose (50 mg / day) in combination with glimepiride, there was no increase in body weight.
Infectious and parasitic diseases: very rarely - nasopharyngitis.
Disorders from the gastrointestinal tract : infrequently - constipation.
Disturbances from the nervous system: often - tremor, dizziness, headache, asthenia.
When using Galvus in a dose of 50 mg 1 or 2 times / day in combination with thiazolidinedione derivatives
In applying the drug Galvus 50 mg / day in combination with pioglitazone frequency of discontinuation due to adverse reactions was 0.7% (Group vildagliptin 100 mg / day + pioglitazone placebo + pioglitazone discontinuations of therapy due to adverse reactions are not mentioned).
In applying the drug Galvus 50 mg / day in combination with pioglitazone 45 mg of hypoglycemia were observed; vildagliptin group (at a dose of 50 mg 2 times a day) + pioglitazone (45 mg) indicated the development of hypoglycemia in 0.6% of cases and patients receiving placebo + pioglitazone 45 mg, - 1.9% of cases. In the group of the drug Galvus were observed for hypoglycemia severe. The average increase versus placebo in body weight in patients receiving Galvus drug dose of 50 mg of 1 or 2 times / day with pioglitazone was +0.1 or +1.3 kg kg respectively.
When adding Galvus drug dose of 50 mg of 1 or 2 times / day for pioglitazone in a dose of 45 mg / day incidence of peripheral edema was 8.2% and 7%, respectively (compared to 2.5% on pioglitazone monotherapy). However, if the initial combination therapy vildagliptin 50 mg 1 or 2 times / day with pioglitazone 45 mg / day development of peripheral edema was observed in 3.5% or 6.1% of patients, respectively (compared to 9.3% on pioglitazone monotherapy at a dose of 30 mg / day).
Violations by vessels: often - peripheral edema.
Violations by the Metabolism and nutrition: often - increase in body weight.
In applying Galvus drug in a dose of 50 mg of 2 times / day in combination with insulin (with or without metformin it)
In applying the drug in combination with insulin (in combination with metformin or without metformin) frequency of discontinuation due to side effects was equal to 0.3% of vildagliptin therapy group was not in the placebo group cases discontinuation.
In applying the drug in combination with insulin (in combination with metformin or without metformin) no increase in risk of hypoglycemia as compared to placebo + the combination of insulin (14% in the vildagliptin group and 16.4% in the placebo group).
In 2 patients in the vildagliptin group and 6 patients in the placebo group developed severe hypoglycemia.
At the time of completion of the study drug had no effect on the average body weight (body mass increased by + 0.6 kg compared with the original in the vildagliptin group and remained unchanged in the placebo group).
Disorders of the nervous system: often - headache, unknown - asthenia.
Disorders of the gastrointestinal tract: often - nausea, gastroesophageal reflux disease; rarely - diarrhea, flatulence.
General disorders and the site of injection : often - chills.
Violations by the Metabolism and nutrition: often - hypoglycemia.
In applying Galvus drug in a dose of 50 mg of 2 times / day in combination with a sulfonylurea and metformin
Cases, discontinuation of the drug-related adverse events in the combination therapy group, vildagliptin, metformin and glimepiride, have been reported. 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).
Disorders of the nervous system: often - dizziness, tremor, asthenia.
Violations by the Metabolism and nutrition: often - hypoglycemia.
Violations of the skin and subcutaneous tissue disorders: often - hyperhidrosis.
Postmarketing studies
During the post-marketing studies, the following adverse reactions (as the messages are received voluntarily from a population of uncertain size, reliably determine the incidence of these adverse events is not possible, in connection with which they are classified as the frequency is unknown): hepatitis (reversible upon termination therapy), rash, pancreatitis, bullous and exfoliative skin lesions, arthralgia, in rare cases severe, myalgia, increased activity of " echenochnyh "enzymes.
The patient should be warned that if any of the above instructions side effects are compounded, or if seen any other side effects not mentioned in the instructions, you should inform your doctor.
CONTRAINDICATIONS
- increased sensitivity of vildagliptin and any other components of the formulation;
- hereditary galactose intolerance, lactase deficiency, glucose-galactose malabsorption;
- pregnancy, breastfeeding (because of lack of relevant data);
- type 1 diabetes;
- 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);
- liver dysfunction, including those with increased activity "liver" enzymes (ALT or AST in 3 or more times the upper limit of normal 3hVGN);
- Chronic heart failure (CHF) IV functional class (FC) of the functional classification of the New York Heart Association (NYHA) (due to lack of clinical trial data on the use of vildagliptin in this patient group);
- Children up to age 18 years (effectiveness and safety of the drug has not been established).
Caution
is recommended with caution in drug Galvus in patients with acute pancreatitis history.
Since the experience with Galvus drug in patients with end-stage CKD on hemodialysis or undergoing hemodialysis is limited, it is recommended the drug be used with caution in these patients.
Since the data on the use of vildagliptin in patients with CHF NYHA class III classification is limited and inconclusive, it is advisable to use caution drug Galvus in patients in this category.
PREGNANCY AND LACTATION
Galvus sufficient for use of these drugs in pregnant women do not have, in connection with which the drug is contraindicated during pregnancy.
In preclinical studies, reproductive toxicity when used in high doses, has been identified, the potential risk for humans is unknown.
The drug Galvus is contraindicated during breast-feeding because it is not known whether vildagliptin passes into breast milk in humans.
APPLICATION FOR FUNCTIONS OF THE LIVER
Since the experience of Galvusa patients with moderate or severe renal impairment (including end-stage renal failure on hemodialysis) is limited, the drug is not recommended for this group of patients.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Galvus not recommended for use in patients with severe hepatic impairment, including patients with elevated liver enzymes (ALT or AST> 2.5 times the ULN).
APPLICATION FOR CHILDREN
The efficacy and safety of the drug in children and adolescents under 18 years of age has not been established.
APPLICATION IN ELDERLY PATIENTS
In elderly patients (≥65 years of age) is not required Galvusa correction mode.
SPECIAL INSTRUCTIONS
In preclinical studies, when used in doses 200 times higher than recommended for humans, the drug did not induce fertility disorders.
If desired insulin preparation Galvus used only in combination with insulin. The drug is contraindicated in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis.
Heart failure
Since the data for vildagliptin use in patients with CHF III NYHA classification by FC (see. Table 1, below) are limited and do not permit a definitive conclusion, it is recommended to use caution Galvus drug in this category of patients.
Vildagliptin is not recommended to use in patients with heart failure NYHA IV FC for classification due to lack of clinical trial data on the use of vildagliptin in this patient group.
Table 1. NYHA functional status of patients with chronic heart failure (modification), NYHA, 1964
functional class (FC) Restriction of physical activity and clinical manifestations
I FC There are no limitations in physical activity. Normal physical activity does not cause pronounced fatigue, weakness, shortness of breath or palpitations.
II FC moderate limitation of physical activity. At rest, any pathological symptoms are absent. Normal physical activity causes weakness, fatigue, palpitations, shortness of breath and other symptoms.
III FC Marked limitation of physical activity. The patient feels comfortable only at rest, but the slightest physical activity lead to the appearance of weakness, palpitations, shortness of breath.
FC IV Inability to carry any load without causing discomfort. Symptoms of cardiac insufficiency are at rest, and are enhanced by any physical activity.
Dysfunction of the liver
Since the rare cases when applying vildagliptin observed increased activity of aminotransferases (usually without clinical manifestations), before applying Galvus preparation, as well as regularly during the first year of the drug (1 every 3 months), it 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 in 3 or more times the ULN confirmed repeated study drug is recommended to cancel.
With the development of jaundice or other signs of liver function abnormalities during treatment with Galvus therapy with the drug should be discontinued immediately. After normalization of liver function indicators drug treatment can not renew.
Hypoglycaemia
It is known that sulfonylureas may provoke the development of hypoglycemia. There is a risk of hypoglycemia, while the use of vildagliptin with sulfonylureas. If necessary, consider reducing the dose of sulfonylurea in order to minimize the risk of hypoglycemia.
Acute pancreatitis
Use of vildagliptin is associated with the risk of acute pancreatitis. It is necessary to inform the patient about the symptoms characteristic of acute pancreatitis. Suspected acute pancreatitis vildagliptin should be abolished. Should not reopen vildagliptin therapy if acute pancreatitis was confirmed. In patients with acute pancreatitis history vildagliptin should be used with caution.
Impact on the ability to drive vehicles and manage mechanisms
Studies on the ability to influence drug Galvus to drive vehicles or operate machinery have not been conducted. With the development of vertigo on the background of the drug patients should not drive vehicles or operate machinery.
OVERDOSE
Vildagliptin is well tolerated in doses up to 200 mg / day.
In applying the drug at a dose of 400 mg / day may experience muscle pain, rarely - light and transient paresthesia, fever, swelling and transient increase in lipase activity (more than 2 times ULN). With increasing doses of vildagliptin and 600 mg / day may develop swelling of limbs, paresthesia and accompanied by increase of CPK activity, C-reactive protein and myoglobin, AST activity. All symptoms of overdose and changes in laboratory parameters reversible upon discontinuation of the drug.
Excretion of the drug from the body by dialysis unlikely. However, the main metabolite of the hydrolysis of vildagliptin (LAY151) can be removed from the body by hemodialysis.
DRUG INTERACTION
Vildagliptin has a low potential for drug interactions.
Since vildagliptin is not a substrate of cytochrome P450 enzyme (CYP), and also did not inhibit or induce these enzymes vildagliptin interaction with drugs that are substrates, inhibitors or inducers of P450 (CYP), it is unlikely. With simultaneous application of vildagliptin also affects the rate of metabolism of drugs that are substrates of enzymes: CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A4 / 5. No clinically significant interaction with vildagliptin drugs most frequently used in the treatment of type 2 diabetes (glibenclamide, pioglitazone, metformin) or having a narrow therapeutic range (amlodipine, digoxin, ramipril, simvastatin, valsartan, warfarin) is not established.
Thiazides, corticosteroids, hormones, thyroid medications, sympathomimetics may reduce the hypoglycaemic effect of vildagliptin, as well as other oral antidiabetic drugs.
The rate of angioedema was higher, while the application of vildagliptin with ACE inhibitors, in this case was similar to that in the control group. In most cases, angioedema was of moderate severity and resolved on their own during the continuation of vildagliptin therapy.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
The preparation should be stored in their original packaging in a dry place inaccessible to children at a temperature not higher than 30 В° C. Shelf life - 3 years. Do not use after the expiration date.
