Galvus®
When using Galvus as monotherapy or in combination with other drugs, most adverse reactions were mild, temporary and did not require discontinuation of therapy. There was no correlation between the frequency of adverse reactions and age, gender, ethnicity, duration of use or dosage regimen.
The incidence of angioedema during therapy with Galvus was >1/10,000, <1/1000 (rare) and was similar to that in the control group. Most often, angioedema was observed when the drug was prescribed in combination with ACE inhibitors. In most cases, angioedema was of moderate severity and disappeared with continued vildagliptin therapy.
During therapy with Galvus, asymptomatic liver dysfunction (including hepatitis) was rarely observed. In most cases, these disorders and deviations of liver function tests from normal resolved independently without complications after discontinuation of drug therapy. When using Galvus at a dose of 50 mg 1 time/day or 2 times/day, the incidence of increased liver enzyme activity (ALT or AST ≥ 3xULN) was 0.2% or 0.3%, respectively (compared to 0.2% in the control group). Increases in liver enzyme activity were in most cases asymptomatic, did not progress, and were not accompanied by cholestatic changes or jaundice.
Determination of the frequency of adverse reactions: very often (≥1/10); often (≥1/100, <1/10), uncommon (≥1/1000, <1/100), rare (≥1/10,000, <1/1000), very rare (≤1/10,000), including individual messages.
When using the drug Galvus as monotherapy
When using the drug Galvus at a dose of 50 mg 1 time / day or 2 times / day, the frequency of discontinuation of therapy due to the development of adverse reactions (0.2% or 0.1%, respectively) was not higher than that in the placebo group (0.6%) or the reference drug (0.5 %).
During monotherapy with Galvus at a dose of 50 mg 1 time/day or 2 times/day, the incidence of hypoglycemia without increasing the severity of the condition was 0.5% (2 out of 409 people) or 0.3% (4 out of 1082), which is comparable with the reference drug and placebo (0.2%). When using the drug Galvus as monotherapy, there was no increase in body weight of patients.
From the nervous system:
often - dizziness; infrequently - headache.
From the digestive system:
infrequently - constipation.
From the body as a whole:
infrequently - peripheral edema.
Long-term clinical studies of up to 2 years did not reveal any additional safety profile deviations or unexpected risks when using vildagliptin as monotherapy.
When using the drug Galvus at a dose of 50 mg 1 time / day or 2 times / day in combination with metformin
When using the drug Galvus at 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 the groups vildagliptin (50 mg 2 times/day) + metformin and placebo + metformin, there were no cases of discontinuation of therapy due to the development of adverse reactions.
When using the drug Galvus at a dose of 50 mg 1 time / day or 2 times / day in combination with metformin, hypoglycemia was observed in 0.9% and 0.5% of cases, respectively; in the placebo + metformin group - 0.4%. There was no development of severe hypoglycemia in the Galvus group. Combination therapy with vildagliptin + metformin did not affect the body weight of patients.
From the nervous system:
often - tremor, dizziness, headache.
Long-term clinical studies of up to 2 years did not reveal any additional safety profile deviations or unexpected risks when using vildagliptin in combination with metformin.
When using the drug Galvus at a dose of 50 mg/day in combination with sulfonylurea derivatives
When using the drug Galvus at 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 receiving Galvus at a dose of 50 mg/day along with glimepiride was 1.2% (compared to 0.6% in the placebo + glimepiride group). There was no development of severe hypoglycemia in the Galvus group.
When using the drug Galvus at the recommended dose (50 mg/day) in combination with glimepiride, there was no increase in patient weight.
From the nervous system:
often - tremor, dizziness, headache.
From the body as a whole:
often - asthenia.
When using the drug Galvus at a dose of 50 mg 1 time / day or 2 times / day in combination with thiazolidinedione derivatives
When using the drug Galvus at a dose of 50 mg/day in combination with pioglitazone, the frequency of discontinuation of therapy due to the development of adverse reactions was 0.7%; In the vildagliptin (50 mg 2 times/day) + pioglitazone and placebo + pioglitazone groups, there were no cases of discontinuation of therapy due to the development of adverse reactions.
When using the drug Galvus at a dose of 50 mg/day in combination with pioglitazone at a dose of 45 mg, hypoglycemia was not observed; in the group of vildagliptin (at a dose of 50 mg 2 times a day) + pioglitazone (at a dose of 45 mg), hypoglycemia was observed in 0.6% of cases, and in patients receiving placebo + pioglitazone at a dose of 45 mg, in 1.9% of cases. There was no development of severe hypoglycemia in the Galvus group. The mean increase in body weight compared to placebo in patients receiving Galvus 50 mg once a day or twice a day with pioglitazone was +0.1 kg or +1.3 kg, respectively.
When Galvus was added at a dose of 50 mg once a day or twice a day to pioglitazone at a dose of 45 mg/day, the incidence of peripheral edema was 8.2% and 7%, respectively (compared to 2.5% with pioglitazone monotherapy). However, when prescribing initial combination therapy with vildagliptin at a dose of 50 mg 1 time / day or 2 times / day together with pioglitazone at a dose of 45 mg / day, peripheral edema was observed in 3.5% or 6.1% of patients, respectively (compared to 9.3% with pioglitazone monotherapy at a dose of 30 mg/day).
From the cardiovascular system:
often - peripheral edema.
From the body as a whole:
often - weight gain.
When using the drug Galvus at a dose of 50 mg 2 times a day in combination with insulin
When the drug was prescribed in combination with insulin (in combination with metformin or without metformin), the rate of discontinuation of therapy due to the development of side effects was 0.3% in the group of patients receiving vildagliptin; in the group receiving placebo, there was no discontinuation of therapy.
When prescribing the drug in combination with insulin (in combination with metformin or without metformin), there was no increase in the risk of hypoglycemia compared with the combination of placebo + insulin (14% in the vildagliptin group and 16.4% in the placebo group). Two patients in the vildagliptin group and 6 patients in the placebo group developed severe hypoglycemia.
At the time of completion of the study, the drug had no effect on average body weight (body weight increased by 0.6 kg compared to baseline in the vildagliptin group, and no changes were noted in the placebo group).
Adverse reactions in patients receiving vildagliptin 50 mg 2 times a day in combination with insulin (with or without metformin)
From the nervous system:
often - headache, chills.
From the digestive system:
often - nausea, gastroesophageal reflux; infrequently - diarrhea, flatulence.
From the side of metabolism:
often - hypoglycemia.
When using the drug Galvus
in
combination with sulfonylureas and metformin
There were no cases of drug withdrawal associated with adverse reactions in the combination therapy group with vildagliptin, metformin and glimepiride. In the combination therapy group with placebo, metformin and glimepiride, the incidence of adverse reactions was 0.6%.
Hypoglycemia was observed in both groups (5.1% in the combination therapy group of vildagliptin, metformin and glimepiride and 1.9% in the combination therapy group of placebo, metformin and glimepiride). There was one episode of severe hypoglycemia in the vildagliptin group.
At the time of completion of the study, no significant effect on body weight was detected (+0.6 kg in the vildagliptin group and -0.1 kg in the placebo group).
Adverse reactions in patients receiving vildagliptin at a dose of 50 mg 2 times a day in combination with metformin and sulfonylureas
From the nervous system:
often - dizziness, tremor.
From the side of metabolism:
often - hypoglycemia.
From the skin and subcutaneous fat
: often - hyperhidrosis.
From the body as a whole:
often - fatigue.
Post-marketing studies
During post-marketing studies, the following adverse reactions were identified: rarely - hepatitis (reversible upon cessation of therapy); frequency unknown - urticaria, pancreatitis, local peeling of the skin or blistering.
Type 2 diabetes mellitus (T2DM) in the elderly population is a serious economic and medical problem, including due to the growing number of this group of patients worldwide [1, 2]. An aging population plays a leading role in the diabetes pandemic, along with obesity and sedentary lifestyles. The prevalence of T2DM increases with age, reaching 20% in the group of people over 70 years of age. Half of patients with T2DM are over 65 years of age [3]. An increased prevalence of cardiovascular risk factors is also common in the elderly. In addition, this group typically experiences high morbidity and mortality due to renal dysfunction, congestive heart failure, psychological and psychiatric disorders, physical inactivity, weakness, and vulnerability [3]. Older people usually take multiple medications, which increases the risk of drug interactions and the development of side effects, including severe hypoglycemia when using antidiabetic drugs [4]. Thus, the management of T2DM among elderly and very elderly patients is quite challenging.
Treatment of elderly patients with T2DM is also complicated by the lack of data from prospective clinical studies on the choice of treatment algorithm and setting therapeutic goals in this population. It should be noted that data from a group of younger patients cannot be automatically transferred to older patients. Moreover, elderly patients represent a fairly heterogeneous group in terms of duration of diabetes, general status, presence of concomitant diseases and therapy. In other words, there are many prerequisites for the development of individualized approaches to the treatment of such patients [5].
The risk of hypoglycemia is probably the factor that most complicates treatment in older people [7]. Hypoglycemia is especially dangerous and has severe consequences for elderly patients who have lost the ability to recognize symptoms indicating their approach [6, 7]. Problems with comorbidities, combined with the risk of hypoglycemia, significantly limit the choice of therapeutic options for the elderly patient population. Recently, interesting data have emerged suggesting that the use of drugs that increase the activity of incretins may provide significant benefits to elderly patients with T2DM, taking into account their glucose-dependent mechanism of action, low risk of hypoglycemia and effective improvement of glycemic control with minimal risk of side effects [ 9]. Drugs in this group improve the sensitivity of α and β cells to glucose by increasing and prolonging the activity of glucagon-like peptide-1 (GLP-1), which in turn modulates the glucose-dependent secretion of insulin and glucagon, maintaining blood sugar levels within physiological limits without increasing the frequency of hypoglycemia.
Features of T2DM in elderly patients. Higher risk and more severe consequences of hypoglycemia
Hypoglycemia is the most common side effect of therapy with antidiabetic drugs, which increase insulin levels independently of blood glucose levels. These drugs include insulin secretagogues, including sulfonylurea derivatives and glinides, as well as insulin preparations. The actual incidence of hypoglycemia is often underestimated because many episodes remain unrecognized [6]. It is known that the frequency of hypoglycemia significantly increases with age, but its actual prevalence in the population of elderly patients is even more difficult to estimate [6, 7]. Indeed, older people who do not have sufficient knowledge about hypoglycemia often incorrectly assess their condition, which leads to an underestimation of the frequency of hypoglycemia [7].
This situation is aggravated by the presence in many elderly patients of cognitive impairment and disorientation, which can be mistaken for hypoglycemia [7]. In such patients, age-related impairment of the ability to recognize oncoming symptoms progresses, and accordingly, the ability to take preventive or therapeutic measures decreases [8]. The consequences of hypoglycemia in the elderly can be significantly more severe compared to the general population. In this case, behavioral disorders are often a consequence of hypoglycemia. Severe episodes of hypoglycemia in such patients can cause hospitalization for fractures after falls and are associated with the development of acute renal failure and severe cardiovascular accidents with high mortality. Patient age was identified as a significant predictor of hypoglycemia requiring medical attention in the ACCORD (Action to Control Cardiovascular Risk in Diabetes) study, which showed a 3% increase in risk with each additional year of life (p < 0.0001) [10] .
Data from the VADT (Veterans Affairs Diabetes Trial) and ACCORD studies evaluating intensive and standard treatment regimens for T2DM emphasize the need to avoid hypoglycemia during treatment [11]. The VADT study showed that a severe episode of hypoglycemia significantly increased the risk of cardiovascular mortality during 3 months of therapy. The ACCORD study found no difference between mortality rates in the intensive and conventional therapy groups. Moreover, the frequency of severe hypoglycemia was associated with a significant increase in mortality, regardless of the intensity of therapy [11].
Data from a study of a cohort that included 16 thousand patients with T2DM from Northern California showed that in elderly patients, a history of 3 severe episodes of hypoglycemia significantly increases the risk of developing dementia [12].
Thus, when treating elderly patients with T2DM, it is always necessary to remember that for them hypoglycemia is associated with a high risk of developing severe complications.
High prevalence of micro- and macrovascular complications and increased risk of functional impairment, including cognitive impairment, in older patients with T2DM
T2DM is associated with the progressive development of micro- and macrovascular complications, the prevalence of which increases with age [4–7], and remains the main cause of mortality and reduced life expectancy in elderly patients [3]. However, in addition to the traditional late complications of diabetes, which are widespread in older patients, this population is at increased risk of developing other equally severe clinical syndromes, such as functional impairment, physical limitations, falls, fractures, cognitive impairment, and depression [3]. Functional disorders are characterized by difficulties in performing routine physical work, which significantly affects the outcome of treatment and the quality of life of patients [3, 4]. With age, patients with T2DM have a higher risk of developing cognitive impairment. In a study by M. Munshi et al. [20] showed that every third patient with T2DM over 70 years of age suffers from intellectual impairment. Depression also often accompanies the course of T2DM and can increase the manifestations of cognitive dissonance, especially with unsatisfactory metabolic control [5, 20].
Heterogeneity of diabetes. the need to select treatment goals in accordance with the functional status
The population of elderly patients with T2DM is a heterogeneous group in terms of duration of diabetes, life expectancy, and the presence of concomitant diseases. The goals of therapy may differ significantly among them, for example, in patients with long-term diabetes and multiple comorbidities compared with patients with recently developed T2DM and generally in good health [5, 12].
It has now been proven that early intensive therapy with strict control goals subsequently provides the so-called. metabolic memory effect. This is shown in a report on a 10-year follow-up of a cohort of patients after completion of the UKPDS (UK Prospective Diabetes Study). In older patients with newly diagnosed T2DM, stricter control goals provided greater benefits, including improvements in cognitive function [10] and overall health. At the same time, for patients with long-term diabetes, a more gentle approach when choosing goals for glycemic control is rational. Currently, the European Society for the Control of Older People with Diabetes recommends flexible treatment goals of a glycated hemoglobin (HbA1c) level of up to 8%, with a particular emphasis on their quality of life, minimizing the risk of hypoglycaemia and other side effects of therapy.
Therapy using incretin drugs in elderly patients with T2DM
Incretins - GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) - are short-acting hormones secreted in the intestine in response to food intake. They provide the first phase of insulin secretion and coordinate the function of islet cells. Of particular importance is the ability of incretins to control the secretion of glucagon by α-cells, as well as the experimentally proven ability to suppress apoptosis and preserve the function of β-cells [13].
Therapy based on incretins (DPP-4 inhibitors and GLP-1 analogues) provides glucose-sensitive modulation of insulin and glucagon secretion. This minimizes the risk of hypoglycemia and maintains glycemic control within physiological limits, in contrast to the use of sulfonylureas and glinides. Such possibilities are of particular interest in the treatment of elderly patients with T2DM [13, 14].
Unlike GLP-1 receptor agonists, DPP-4 inhibitors are taken orally. They enhance and prolong the action of endogenous incretins in physiological concentrations. Therapy with DPP-4 inhibitors is associated with a minimal risk of hypoglycemia and does not cause weight gain [13–15]. Unlike GLP-1 analogues, DPP-4 inhibitors do not slow down the rate of gastric emptying without causing gastrointestinal side effects. Currently, the following DPP-4 inhibitors are used in the treatment of T2DM: vildagliptin (Galvus), sitagliptin (Januvia) and saxagliptin (Ongliza). Several more inhibitors are under development (alogliptin, linagliptin, etc.). Vildagliptin is currently used in 75 countries around the world.
Data on the pharmacokinetics of vildagliptin showed that the patient’s age does not affect its properties and parameters of elimination from the body [13]. Vildagliptin breaks down by hydrolysis into pharmacologically inactive metabolites. The primary route of elimination is the kidneys: 85% of the administered dose is excreted in the urine in the form of inactive components [13, 14]. Vildagliptin is not currently approved for use in patients with glomerular filtration rate (GFR) below 50 mL/min, and no dose adjustment is required if GFR is above this level. Two large clinical trials are currently underway to evaluate the long-term safety of vildagliptin in patients with moderate to severe renal impairment. The drug is not metabolized through the cytochrome system (CYP450) and does not interact with drugs that are most often used in the treatment of elderly patients [14]. In addition, vildagliptin does not bind to plasma proteins, which also reduces the risk of drug-drug interactions [13].
Clinical data on the use of vildagliptin in a population of elderly patients with T2DM
A large clinical trial program for vildagliptin was conducted to evaluate the treatment of elderly patients with T2DM. This made it possible to conduct an expanded analysis in the group of patients over 65 years of age (374 people) and over 75 years of age (1890 people). All patients initially had cardiovascular risk factors and numerous concomitant diseases, for which intensive drug therapy was carried out. A subgroup of older patients had lower HbA1c, fasting blood glucose (FBG) and body weight compared to younger patients. Treatment with vildagliptin (50 mg twice daily) for 24 weeks led to a significant improvement in glycemic control with a decrease in HbA1c and BGL levels in both individuals over 75 years of age (by 1.2% and 1.5 mmol/L, respectively) and in younger patients (by 0.9% and 1.1 mmol/l) [16].
In addition, this improvement in carbohydrate metabolism was accompanied by a slight decrease in body weight (0.9 kg in patients over 75 years of age and 0.2 kg in those under 75 years of age).
The therapy was well tolerated by all patients and was not accompanied by significant side effects. In patients over 75 years of age with mild renal failure, there was no increase in the incidence of side effects of therapy compared with a similar group of patients under 75 years of age and without impaired renal function. In the group of patients over 75 years of age, there were practically no confirmed episodes of hypoglycemia (0.8%), as well as in the group of patients under 75 years of age (0%; see table). The data obtained allowed us to obtain approval for the use of vildagliptin in the population of elderly patients.
. Frequency of hypoglycemia during monotherapy with vildagliptin and in combination with other oral hypoglycemic drugs.
The data presented above were confirmed in randomized, double-blind studies comparing therapy with vildagliptin (50 mg twice daily) or metformin (1500 mg/day) conducted for 6 months in 335 patients with T2DM over 65 years of age who had not previously received treatment [15 ]. The average age of the patients was 71 years (65–93 years), the initial HbA1c level was 7.7%, and the body mass index was 29.6 kg/m2. Of the study participants, 92% of patients received concomitant therapy, 50% had mild renal failure (GFR-50–80 ml/min/1.73 m2). After 6 months of treatment, HbA1c levels decreased approximately to the same extent during therapy with vildagliptin (by 0.64%) and metformin (by 0.75%). Mean HbA1c values at 6 months were 7.1 and 7.0% on vildagliptin and metformin therapy, respectively. Despite improved control of T2DM, not a single episode of hypoglycemia was recorded in the vildagliptin therapy group and only 2 (1.2%) episodes in the metformin group. Treatment with vildagliptin was associated with a lower incidence of adverse events (44.3 versus 50.3%) and discontinuation of therapy (4.2 versus 7.9%) compared to metformin. Treatment discontinuations were primarily due to gastrointestinal side effects (diarrhea incidence was 3.0% with vildagliptin and 24.3% with metformin).
Recently, the results of another study evaluating vildagliptin therapy in patients with T2DM over the age of 75 years were published [21]. The results of this analysis demonstrated the effectiveness and good tolerability of vildagliptin in patients who averaged 77 years of age. These patients had a lower degree of obesity compared to younger ones (body mass index - 29.4 and 31.5 kg/m2, respectively) and a higher frequency of concomitant diseases (30% had a history of cardiovascular diseases, 70% had a history of renal disease). failure). Vildagliptin therapy provided a reduction in HbA1c levels by 0.9% (initial 8.3%) in monotherapy and by 1.1% (initial 8.5%) in combination with metformin. This improvement was comparable to the dynamics of glycemia in patients under 75 years of age. No hypoglycemic episodes were recorded. The overall incidence of adverse events and the incidence of serious adverse events were low and comparable in the group of patients older and younger than 75 years.
Data on the minimal risk of hypoglycemia among elderly patients receiving vildagliptin therapy were confirmed in another study that included patients over 65 years of age (144 people) with a short duration of T2DM (initial mean HbA1c level = 6.7%). During two years of therapy (one year of follow-up and one year of extended follow-up), no patients in the vildagliptin group reported episodes of hypoglycemia, despite improved glycemic control compared with placebo (a significant difference in HbA1c levels after 2 years of therapy was 0.5%) [ 17].
Another study of adding vildagliptin to insulin therapy included 296 patients with T2DM, one third of whom were over 65 years of age (mean age 71 years) [18]. The duration of the disease was 18 years, of which for the last 7 years patients received insulin (average dose - 66 U/day, initial HbA1c level = 8.4%). After 6 months of therapy in the group of elderly patients, the HbA1c level decreased by 0.7% from baseline (p < 0.001 compared with placebo), and the addition of vildagliptin was accompanied by a decrease in the frequency of hypoglycemia compared with placebo: in 13% of patients in the vildagliptin + insulin group compared with 26% in the placebo + insulin group [18]. In a double-blind extended observation period, HbA1c levels decreased by 0.9% from baseline after a year of therapy with vildagliptin (50 mg twice daily; Fig. 1) [19].
A study of the effectiveness of the combination of vildagliptin + metformin compared with the combination of glimepiride + metformin showed a 10-fold reduction in the risk of hypoglycemia in a subgroup of 172 patients with T2DM aged 65 years [19]. After a year of observation, improvement in glycemic control was noted with both treatment options. But the overall incidence of hypoglycemia was 1.4% in the vildagliptin group versus 15.6% in the glimepiride group. The advantage of vildagliptin was confirmed after a year of extended follow-up: in elderly patients, the incidence of hypoglycemia with its use was 2.1 versus 17.5% during therapy with glimepiride (p < 0.001; Fig. 2).
The low incidence of hypoglycemia during vildagliptin therapy can be explained by improved counterregulation of insulin secretion. Data have been published that, under conditions of a hyperinsulinemic hypoglycemic clamp, vildagliptin significantly increases glucagon levels compared to placebo (by 38%), thereby improving the sensitivity and response of β-cells to stimulation in a state of hypoglycemia [14].
Conclusion
Elderly patients with T2DM are most susceptible to the negative effects of hypoglycemia. They have a significantly reduced ability to recognize the onset of hypoglycemia, which leads to more severe and prolonged episodes with significant complications. Studies in older patients with T2DM have shown that the use of DPP-4 inhibitors is beneficial in the treatment of this cohort of patients. DPP-4 inhibitors provide a physiological enhancement of incretin activity, are well tolerated and have a pronounced hypoglycemic effect. The main positive properties of DPP-4 inhibitors include a low incidence of hypoglycemia and a neutral effect on body weight, which is of particular importance in the treatment of elderly patients with T2DM. High clinical efficacy of vildagliptin therapy has been demonstrated in the population of patients with T2DM over 75 years of age.
Information about the author: Mikhail Borisovich Antsiferov – Doctor of Medical Sciences, Professor, Chief Physician of the Endocrinological Dispensary of the Moscow Department of Health. Email
Buy Galvus tablets 50 mg No. 28 in pharmacies
Galvus Buy Galvus in pharmacies DOSAGE FORMS tablets 50mg
MANUFACTURERS Novartis Pharma Stein AG (Switzerland)
GROUP Hypoglycemic agents - dipeptidyl peptidase-4 inhibitors
COMPOSITION Active substance: Vildagliptin.
INTERNATIONAL NON-PROPENTED NAME Vildagliptin
SYNONYMS Hemofer prolongatum, PMS-iron sulfate, Tardiferon, Ferro-gradumet, Ferrogradumet
PHARMACOLOGICAL ACTION Hypoglycemic drug, selective inhibitor of dipeptidyl peptidase-4 (DPP-4). Rapid and complete inhibition of DPP-4 activity causes an increase in both basal and meal-stimulated secretion of glucagon-like peptide type 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) from the intestine into the systemic circulation throughout the day. By increasing the levels of GLP-1 and GIP, vildagliptin causes an increase in the sensitivity of pancreatic beta cells to glucose, which leads to an improvement in glucose-dependent insulin secretion. Vildagliptin improves pancreatic beta cell function. By increasing endogenous GLP-1 levels, vildagliptin increases alpha cell sensitivity to glucose, resulting in improved glucose-dependent regulation of glucagon secretion. Reducing the level of excess glucagon during meals causes a decrease in insulin resistance. An increase in the insulin/glucagon ratio against the background of hyperglycemia, caused by an increase in the levels of GLP-1 and GIP, causes a decrease in glucose production by the liver both during the prandial period and after a meal, which leads to a decrease in plasma glucose levels. Vildagliptin is rapidly absorbed when taken orally. After oral administration on an empty stomach, maximum concentration is achieved after 1 hour 45 minutes. Plasma protein binding is low. Most of vildagliptin is excreted by the kidneys (85%) and a small part through the intestines (15%). The half-life is approximately 3 hours.
INDICATIONS FOR USE Diabetes mellitus type 2: 1. As monotherapy in combination with diet therapy and exercise. 2. As part of two-component combination therapy with metformin, sulfonylurea derivatives, thiazolidinedione or insulin in case of ineffectiveness of diet therapy, exercise and monotherapy of these drugs.
CONTRAINDICATIONS Hypersensitivity to vildagliptin and other components of the drug, children under 18 years of age, severe hepatic or liver failure, galactose intolerance, lactase deficiency, glucose-galactose malabsorption, pregnancy, breastfeeding. The drug should not be used in patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis.
SIDE EFFECTS: Liver dysfunction, including hepatitis, has rarely been reported during treatment with Galvus. In most cases, these disorders and deviations from the norm in liver function indicators resolved independently without complications after discontinuation of drug therapy. Monotherapy with Galvus: From the central nervous system: often dizziness, sometimes headache. From the digestive system: sometimes constipation. From the body as a whole: sometimes peripheral edema. In combination with metformin: From the central and peripheral nervous system: frequent tremor, dizziness, headache. In combination with thiazolidinedione derivatives: From the cardiovascular system: often peripheral edema. From the body as a whole: often - increase in body weight. In combination with insulin: From the central nervous system: often - headache. From the digestive system: frequent nausea, flatulence, gastroesophageal reflux disease. Metabolic and nutritional disorders: often hypoglycemia.
INTERACTIONS The drug has a low potential for drug interactions. No clinically significant interaction of Vildagliptin with drugs most commonly used in the treatment of type 2 diabetes mellitus (glibenclamide, pioglitazone, metformin) or those with a narrow therapeutic range (amlodipine, digoxin, ramipril, simvastatin, valsartan, warfarin) has been established.
DOSAGE AND ADMINISTRATION Galvus is taken orally, regardless of food intake. The dosage regimen of the drug is selected individually depending on the effectiveness and tolerability. The recommended dose of the drug when used as monotherapy or as part of two-component combination therapy with metformin, thiazolidinedione or insulin is 50 mg or 100 mg per day. In patients with more severe type 2 diabetes mellitus receiving insulin treatment, Galvus is recommended to be used at a dose of 100 mg per day.
OVERDOSE Symptoms: paresthesia, fever, edema, transistor increase in the concentration of lipase, creatine phosphokinase, alanine aminotransferase, C-reactive protein, myoglobin. All symptoms disappear after stopping the drug. Removal of the drug from the body by dialysis is unlikely, but the main hydrolytic metabolite of vildagliptin (LAY151) can be removed from the body by hemodialysis.
SPECIAL INSTRUCTIONS Before treatment, as well as during treatment, it is necessary to determine biochemical indicators of liver function. If jaundice or other signs of liver dysfunction develop while using Galvus, treatment should be discontinued. If dizziness develops during treatment with the drug, you should not drive or operate machinery.
STORAGE CONDITIONS: In a dry place at a temperature not exceeding 30°C.
