Composition, structure and packing
Tablets are white to almost white, round, biconvex, on the one hand are stamped "15", on the other - "ACTOS".
1 tab. pioglitazone (in the form of hydrochloride) 15 mg.
Excipients: lactose monohydrate, gidroksipropiltsellyuloza, calcium carboxymethylcellulose, magnesium stearate.
Tablets are white to almost white, round, biconvex, on the one hand are stamped "30", on the other - "ACTOS".
1 tab. pioglitazone (in the form of hydrochloride) 30 mg.
Excipients: lactose monohydrate, gidroksipropiltsellyuloza, calcium carboxymethylcellulose, magnesium stearate.
Tablets are white to almost white, round, biconvex, on the one hand are stamped "45", on the other - "ACTOS".
1 tab. pioglitazone (in the form of hydrochloride) 45 mg.
Excipients: lactose monohydrate, gidroksipropiltsellyuloza, calcium carboxymethylcellulose, magnesium stearate.
Clinico-pharmacological group: oral hypoglycemic drug.
Pharmacological action
Oral hypoglycemic drug, a derivative tiazolidindionovogo series. It is a powerful and highly selective agonist of gamma-activated receptors proliferatorom peroxisomes (PPARγ). PPARγ-receptors are found in adipose, muscle and liver. Activation of PPARγ nuclear receptors modulates the transcription of several genes that are sensitive to insulin, is involved in controlling glucose and lipid metabolism. Aktos reduces insulin resistance in peripheral tissues and liver, and the consequence is an increase in consumption of Insulin and glucose reductions in glucose from the liver. Unlike drugs sulfonylureas, pioglitazone does not stimulate the secretion of insulin β-cells of the pancreas.
In diabetes type 2 reduce insulin resistance under the action of the drug Aktos causes a decrease in blood glucose concentration, lower insulin levels in plasma and hemoglobin A1c (glycosylated hemoglobin, HbA1c). As monotherapy and in combination with sulfonylurea medications, metformin or insulin drug improves control of blood sugar levels.
In diabetes type 2 with lipid disorders in the background of treatment with the decrease of triglycerides and increase levels of HDL. The level of LDL and total cholesterol in these patients does not change.
In applying the drug Aktos patients with diabetes mellitus type 2, conducted by echocardiographic examination showed no noticeable increase in the average left ventricular mass index or a noticeable decrease in the average cardiac index.
Pharmacokinetics
Absorption
Once inside an empty stomach pioglitazone found in plasma after 30 min. Cmax in plasma achieved in 2 hours when a meal there was a slight increase in the time to achieve Cmax to 3-4 h, but the degree of absorption was not changed.
Distribution
After receiving a single dose of an apparent Vd pioglitazone averaged 0.63 ± 0.41 (mean ± SD-standard deviation) L / kg. Pioglitazone significantly associated with the protein human serum (> 99%), mainly to albumin and to a lesser extent - with other proteins of serum. Pioglitazone metabolites M-III and M-IV also significantly associated with serum albumin (> 98%). As in healthy volunteers and patients with insulin-dependent diabetes mellitus (type II) equilibrium concentration of pioglitazone is about 30-50% of the peak concentrations of total pioglitazone serum and 20% -25% of the AUC.
Metabolism
Pioglitazone extensively metabolized in the liver by hydroxylation and oxidation reactions with the formation of metabolites. Metabolites M-II, M-IV (hydroxide derivatives of pioglitazone) and M-III (keto-derivatives of pioglitazone) exhibit pharmacological activity in models of type 2 diabetes in animals. The metabolism of pioglitazone in the liver occurs with the participation of major cytochrome P450 isoenzymes (CYP2C8 and CYP3A4). In the in vitro pioglitazone did not inhibit the activity of P450. Studies in vivo were not conducted.
Withdrawal
T1 / 2 of unchanged pioglitazone is 3-7 hours, total pioglitazone (pioglitazone and active metabolites) - 16-24 hours Clearance pioglitazone is 5-7 L / h. After oral administration about 15-30% of the dose pioglitazone detected in the urine.
Urinary negligible amount of pioglitazone, mostly in the form of metabolites and their conjugates. It is believed that the ingestion of large doses is excreted in the bile in unchanged form, and in the form of metabolites and excreted in feces. The concentrations of pioglitazone and active metabolites in the serum remained at a high level 24 h after a single dose daily dose.
Statement
Diabetes mellitus type 2:
as an adjunct to diet and exercise;
for monotherapy or in combination therapy with derivatives of sulfonylurea, metformin or insulin in the case of failure of diet therapy, exercise, and the appointment of monotherapy with one of the above drugs.
Dosage regimen
Dose was set individually. Aktos appointed interior 1 time / day irrespective of food intake. For the treatment of type 2 diabetes as monotherapy Aktos administered in a dose of 15 mg or 30 mg 1 time / day.
If necessary, the dose may be gradually increased to a maximum equal to 45 mg / day.
When failure of monotherapy should be the possibility of combination therapy.
Combined therapy c sulfonylurea derivatives Aktos administered in a dose of 15 mg or 30 mg 1 time / day. At the beginning of treatment with sulfonylurea derivative Aktos dose can be left unchanged, with the development of hypoglycemia last dose should be reduced. In combination with metformin Aktos prescribe a dose of 15 mg or 30 mg 1 time / day. At the beginning of treatment with Aktos dose of metformin can be left unchanged. The risk of hypoglycemia in this combination is negligible, so the need for dose adjustment of metformin is unlikely. In combination with insulin Aktos prescribe a dose of 15 mg or 30 mg 1 time / day. At the beginning of treatment with insulin Aktos be left unchanged.
With the development of hypoglycemia and decrease the concentration of glucose in plasma to below 100 mg / dl, the insulin dose can be reduced by 10-25%. Further adjustment of insulin dose should be individually tailored to the level of glycemia.
Combined therapy Aktos maximum dose is 30 mg / day. In patients with renal insufficiency correction dose Aktos not required.
Side effect
On the part of metabolism: possible development of hypoglycaemia (mild to severe) - 1% of patients receiving placebo, 2% of cases applying Aktosa in combination with a sulfonylurea derivative, 5% of cases with the use of placebo in combination with insulin, 8 % of cases applying Aktosa 15 mg in combination with insulin, 15% of cases with a combination of Aktosa 30 mg of insulin; edema - 4.8% in monotherapy, 15.3% - in combination with insulin.
On the part of the hemopoietic system: 1-1.6% - anemia; 2-4% - reduction of hemoglobin and hematocrit. These changes were mainly observed after 4-12 weeks after starting treatment, remained relatively constant and were not associated with any clinically significant hematological effects.
From the laboratory parameters: increasing reported cases of ALT ≥ 3 times (0.25%), which were reversible and not associated with the use of the drug Aktos; observed rare cases of a temporary increase in the level of CK, who had no clinical implications and the relationship that the drug intake Aktos not installed, the average values of bilirubin, AST, ALT, alkaline phosphatase and GGT decreased at the end of treatment compared with those of before treatment.
Contraindications
diabetes mellitus type 1;
diabetic ketoacidosis;
Pregnancy
lactation (breastfeeding);
established by Hypersensitivity to pioglitazone or to one of the components of the drug.
Pregnancy and lactation
There are no adequate and strictly controlled studies safety of Aktosa during pregnancy was conducted.
Since the currently available information strongly indicates that elevated blood glucose levels during pregnancy is associated with an increase in the incidence of congenital anomalies, as well as increased incidence of pathology in the neonatal period and an increase in mortality during pregnancy is recommended to use insulin.
It is not known whether pioglitazone is allocated with breast milk, so if you need to apply Aktosa lactating breast-feeding should be discontinued.
Application for violations of liver function should not assign a drug in the presence of clinical manifestations of liver disease in the active phase or an increase in the activity of ALT was 2.5 times higher than the upper limit of normal. In moderately elevated liver enzymes (ALT less than 2.5 times the upper limit of normal) before treatment or during treatment with Aktos patients should be examined to determine the reasons for improved performance.
With a moderate increase in liver enzymes should be cautious to begin or continue treatment drug Aktos. In this case, we recommend more frequent monitoring of clinical picture and study the level of liver enzymes.
Application for violations of renal function in patients with renal insufficiency correction dose Aktos not required.
Cautions
In a set of measures for the treatment of type 2 diabetes mellitus in addition to taking the drug Aktos should include the recommended diet therapy and exercise. This is important not only in the early treatment of diabetes type 2, but also to maintain the effectiveness of drug therapy.
The effectiveness of drug treatment is preferable to assess the level of HbA1c, which is the most appropriate indicator of glycemic control for a long time, compared with the definition of only fasting plasma glucose. HbA1c reflects glycemia over the past 2-3 months.
Treatment with Aktos recommended for a sufficient time to assess changes in levels of HbA1c (3 months), if this is not observed deterioration of glycemic control.
You should not assign the drug in the presence of clinical manifestations of liver disease in the active phase or by increasing the activity of ALT was 2.5 times higher than the upper limit of normal.
In moderately elevated liver enzymes (ALT less than 2.5 times the upper limit of normal) before treatment or during treatment with Aktos patients should be examined to determine the reasons for improved performance.
With a moderate increase in liver enzymes should be cautious to begin or continue treatment drug Aktos. In this case, we recommend more frequent monitoring of clinical picture and study the level of liver enzymes.
In the case of increased activity of transaminases in serum (ALT> 2.5 times the upper limit of normal) patients receiving the drug Aktos monitoring of liver function should be held more frequently and for as long as the level does not return to normal or to the indicators that have been observed prior to treatment . If ALT exceeds 3 times the upper limit of normal, then re-test to determine the activity of ALT should be held as soon as possible. If ALT remained at 3 times the upper limit of normal, treatment drug Aktos should be discontinued. During treatment for suspected violations of the development of liver function (nausea, vomiting, abdominal pain, fatigue, lack of appetite, dark urine) should identify indicators of liver function tests.
The issue of continuation therapy with Aktos should be taken on the basis of clinical data with respect to laboratory parameters. In case of jaundice treatment for drug should be discontinued.
In the study of liver function in patients taking Aktos, had not received evidence that the drug has Hepatotoxic effects or causes an increase in the activity of ALT.
Precautions should be appointed Aktos patients with edema. The development of anemia, lower hemoglobin and hematocrit decrease may be associated with increased plasma volume and not associated with any clinically significant hematological effects.
In patients with insulin resistance and anovulyatornym cycle in premenopauznom period thiazolidinedione treatment, including drug Aktos may cause ovulation. The consequence of greater sensitivity to insulin in these patients is the risk of pregnancy, unless you use adequate contraception. Clinical studies using the drug Aktos in a dose of 30 mg / day in combination with other hypoglycemic funds were not conducted. Data on the use of the drug Aktos in combination with other drugs thiazolidinediones are not available.
Monitoring of laboratory parameters
Prior to treatment with Aktos, during the first year of treatment (every 2 months) and then periodically monitor the activity of ALT should be.
Use in Pediatrics
Data on the safety and efficacy of the drug Aktos in children and adolescents under the age of 18 years are not available, so the use of the drug Aktos among these patients is not recommended.
Overdose
There was one case of overdosing Aktos (receiving 120 mg / day). It is not mentioned any specific clinical symptoms.
Treatment: symptomatic therapy of conduct depending on the clinical manifestations.
Drug Interactions
Effect Aktos on the effectiveness of contraceptives for oral administration is not known. However, the application of other derivative thiazolidinediones with oral contraceptives was reduced concentrations of ethinyl estradiol and noretindrona in plasma by approximately 30%.
Therefore, patients receiving Aktos and oral contraceptives may decrease the effectiveness of contraception. At the same time taking the drug Aktos (45 mg / day) and glipizida (5 mg / day) for 7 days was not observed changes in the equilibrium state pharmacokinetics glipizida.
Single dose of metformin (1000 mg) on the background of 7-day admission Aktosa a dose of 45 mg / day did not cause changes in the pharmacokinetics of metformin.
At the same time taking the drug Aktos (45 mg / day) and digoxin (0.25 mg / day) for 7 days was not observed changes in the equilibrium state pharmacokinetics of digoxin.
With simultaneous use of the drug Aktos (45 mg / day) and warfarin for 7 days was not observed changes in the equilibrium state pharmacokinetics of warfarin. In addition, Aktos exerted no distinct effect on the prothrombin time in patients who underwent long-term treatment with warfarin.
Ketoconazole inhibits 85% of pioglitazone metabolism in the liver in vitro. Patients receiving ketoconazole simultaneously with the drug Aktos should be conducted more regularly glycemic control.
Terms and Conditions of storage
The drug should be stored at room temperature between 15 ° to 30 ° C in tightly closed containers. Protect from moisture. Shelf life - 3 years.
Tablets are white to almost white, round, biconvex, on the one hand are stamped "15", on the other - "ACTOS".
1 tab. pioglitazone (in the form of hydrochloride) 15 mg.
Excipients: lactose monohydrate, gidroksipropiltsellyuloza, calcium carboxymethylcellulose, magnesium stearate.
Tablets are white to almost white, round, biconvex, on the one hand are stamped "30", on the other - "ACTOS".
1 tab. pioglitazone (in the form of hydrochloride) 30 mg.
Excipients: lactose monohydrate, gidroksipropiltsellyuloza, calcium carboxymethylcellulose, magnesium stearate.
Tablets are white to almost white, round, biconvex, on the one hand are stamped "45", on the other - "ACTOS".
1 tab. pioglitazone (in the form of hydrochloride) 45 mg.
Excipients: lactose monohydrate, gidroksipropiltsellyuloza, calcium carboxymethylcellulose, magnesium stearate.
Clinico-pharmacological group: oral hypoglycemic drug.
Pharmacological action
Oral hypoglycemic drug, a derivative tiazolidindionovogo series. It is a powerful and highly selective agonist of gamma-activated receptors proliferatorom peroxisomes (PPARγ). PPARγ-receptors are found in adipose, muscle and liver. Activation of PPARγ nuclear receptors modulates the transcription of several genes that are sensitive to insulin, is involved in controlling glucose and lipid metabolism. Aktos reduces insulin resistance in peripheral tissues and liver, and the consequence is an increase in consumption of Insulin and glucose reductions in glucose from the liver. Unlike drugs sulfonylureas, pioglitazone does not stimulate the secretion of insulin β-cells of the pancreas.
In diabetes type 2 reduce insulin resistance under the action of the drug Aktos causes a decrease in blood glucose concentration, lower insulin levels in plasma and hemoglobin A1c (glycosylated hemoglobin, HbA1c). As monotherapy and in combination with sulfonylurea medications, metformin or insulin drug improves control of blood sugar levels.
In diabetes type 2 with lipid disorders in the background of treatment with the decrease of triglycerides and increase levels of HDL. The level of LDL and total cholesterol in these patients does not change.
In applying the drug Aktos patients with diabetes mellitus type 2, conducted by echocardiographic examination showed no noticeable increase in the average left ventricular mass index or a noticeable decrease in the average cardiac index.
Pharmacokinetics
Absorption
Once inside an empty stomach pioglitazone found in plasma after 30 min. Cmax in plasma achieved in 2 hours when a meal there was a slight increase in the time to achieve Cmax to 3-4 h, but the degree of absorption was not changed.
Distribution
After receiving a single dose of an apparent Vd pioglitazone averaged 0.63 ± 0.41 (mean ± SD-standard deviation) L / kg. Pioglitazone significantly associated with the protein human serum (> 99%), mainly to albumin and to a lesser extent - with other proteins of serum. Pioglitazone metabolites M-III and M-IV also significantly associated with serum albumin (> 98%). As in healthy volunteers and patients with insulin-dependent diabetes mellitus (type II) equilibrium concentration of pioglitazone is about 30-50% of the peak concentrations of total pioglitazone serum and 20% -25% of the AUC.
Metabolism
Pioglitazone extensively metabolized in the liver by hydroxylation and oxidation reactions with the formation of metabolites. Metabolites M-II, M-IV (hydroxide derivatives of pioglitazone) and M-III (keto-derivatives of pioglitazone) exhibit pharmacological activity in models of type 2 diabetes in animals. The metabolism of pioglitazone in the liver occurs with the participation of major cytochrome P450 isoenzymes (CYP2C8 and CYP3A4). In the in vitro pioglitazone did not inhibit the activity of P450. Studies in vivo were not conducted.
Withdrawal
T1 / 2 of unchanged pioglitazone is 3-7 hours, total pioglitazone (pioglitazone and active metabolites) - 16-24 hours Clearance pioglitazone is 5-7 L / h. After oral administration about 15-30% of the dose pioglitazone detected in the urine.
Urinary negligible amount of pioglitazone, mostly in the form of metabolites and their conjugates. It is believed that the ingestion of large doses is excreted in the bile in unchanged form, and in the form of metabolites and excreted in feces. The concentrations of pioglitazone and active metabolites in the serum remained at a high level 24 h after a single dose daily dose.
Statement
Diabetes mellitus type 2:
as an adjunct to diet and exercise;
for monotherapy or in combination therapy with derivatives of sulfonylurea, metformin or insulin in the case of failure of diet therapy, exercise, and the appointment of monotherapy with one of the above drugs.
Dosage regimen
Dose was set individually. Aktos appointed interior 1 time / day irrespective of food intake. For the treatment of type 2 diabetes as monotherapy Aktos administered in a dose of 15 mg or 30 mg 1 time / day.
If necessary, the dose may be gradually increased to a maximum equal to 45 mg / day.
When failure of monotherapy should be the possibility of combination therapy.
Combined therapy c sulfonylurea derivatives Aktos administered in a dose of 15 mg or 30 mg 1 time / day. At the beginning of treatment with sulfonylurea derivative Aktos dose can be left unchanged, with the development of hypoglycemia last dose should be reduced. In combination with metformin Aktos prescribe a dose of 15 mg or 30 mg 1 time / day. At the beginning of treatment with Aktos dose of metformin can be left unchanged. The risk of hypoglycemia in this combination is negligible, so the need for dose adjustment of metformin is unlikely. In combination with insulin Aktos prescribe a dose of 15 mg or 30 mg 1 time / day. At the beginning of treatment with insulin Aktos be left unchanged.
With the development of hypoglycemia and decrease the concentration of glucose in plasma to below 100 mg / dl, the insulin dose can be reduced by 10-25%. Further adjustment of insulin dose should be individually tailored to the level of glycemia.
Combined therapy Aktos maximum dose is 30 mg / day. In patients with renal insufficiency correction dose Aktos not required.
Side effect
On the part of metabolism: possible development of hypoglycaemia (mild to severe) - 1% of patients receiving placebo, 2% of cases applying Aktosa in combination with a sulfonylurea derivative, 5% of cases with the use of placebo in combination with insulin, 8 % of cases applying Aktosa 15 mg in combination with insulin, 15% of cases with a combination of Aktosa 30 mg of insulin; edema - 4.8% in monotherapy, 15.3% - in combination with insulin.
On the part of the hemopoietic system: 1-1.6% - anemia; 2-4% - reduction of hemoglobin and hematocrit. These changes were mainly observed after 4-12 weeks after starting treatment, remained relatively constant and were not associated with any clinically significant hematological effects.
From the laboratory parameters: increasing reported cases of ALT ≥ 3 times (0.25%), which were reversible and not associated with the use of the drug Aktos; observed rare cases of a temporary increase in the level of CK, who had no clinical implications and the relationship that the drug intake Aktos not installed, the average values of bilirubin, AST, ALT, alkaline phosphatase and GGT decreased at the end of treatment compared with those of before treatment.
Contraindications
diabetes mellitus type 1;
diabetic ketoacidosis;
Pregnancy
lactation (breastfeeding);
established by Hypersensitivity to pioglitazone or to one of the components of the drug.
Pregnancy and lactation
There are no adequate and strictly controlled studies safety of Aktosa during pregnancy was conducted.
Since the currently available information strongly indicates that elevated blood glucose levels during pregnancy is associated with an increase in the incidence of congenital anomalies, as well as increased incidence of pathology in the neonatal period and an increase in mortality during pregnancy is recommended to use insulin.
It is not known whether pioglitazone is allocated with breast milk, so if you need to apply Aktosa lactating breast-feeding should be discontinued.
Application for violations of liver function should not assign a drug in the presence of clinical manifestations of liver disease in the active phase or an increase in the activity of ALT was 2.5 times higher than the upper limit of normal. In moderately elevated liver enzymes (ALT less than 2.5 times the upper limit of normal) before treatment or during treatment with Aktos patients should be examined to determine the reasons for improved performance.
With a moderate increase in liver enzymes should be cautious to begin or continue treatment drug Aktos. In this case, we recommend more frequent monitoring of clinical picture and study the level of liver enzymes.
Application for violations of renal function in patients with renal insufficiency correction dose Aktos not required.
Cautions
In a set of measures for the treatment of type 2 diabetes mellitus in addition to taking the drug Aktos should include the recommended diet therapy and exercise. This is important not only in the early treatment of diabetes type 2, but also to maintain the effectiveness of drug therapy.
The effectiveness of drug treatment is preferable to assess the level of HbA1c, which is the most appropriate indicator of glycemic control for a long time, compared with the definition of only fasting plasma glucose. HbA1c reflects glycemia over the past 2-3 months.
Treatment with Aktos recommended for a sufficient time to assess changes in levels of HbA1c (3 months), if this is not observed deterioration of glycemic control.
You should not assign the drug in the presence of clinical manifestations of liver disease in the active phase or by increasing the activity of ALT was 2.5 times higher than the upper limit of normal.
In moderately elevated liver enzymes (ALT less than 2.5 times the upper limit of normal) before treatment or during treatment with Aktos patients should be examined to determine the reasons for improved performance.
With a moderate increase in liver enzymes should be cautious to begin or continue treatment drug Aktos. In this case, we recommend more frequent monitoring of clinical picture and study the level of liver enzymes.
In the case of increased activity of transaminases in serum (ALT> 2.5 times the upper limit of normal) patients receiving the drug Aktos monitoring of liver function should be held more frequently and for as long as the level does not return to normal or to the indicators that have been observed prior to treatment . If ALT exceeds 3 times the upper limit of normal, then re-test to determine the activity of ALT should be held as soon as possible. If ALT remained at 3 times the upper limit of normal, treatment drug Aktos should be discontinued. During treatment for suspected violations of the development of liver function (nausea, vomiting, abdominal pain, fatigue, lack of appetite, dark urine) should identify indicators of liver function tests.
The issue of continuation therapy with Aktos should be taken on the basis of clinical data with respect to laboratory parameters. In case of jaundice treatment for drug should be discontinued.
In the study of liver function in patients taking Aktos, had not received evidence that the drug has Hepatotoxic effects or causes an increase in the activity of ALT.
Precautions should be appointed Aktos patients with edema. The development of anemia, lower hemoglobin and hematocrit decrease may be associated with increased plasma volume and not associated with any clinically significant hematological effects.
In patients with insulin resistance and anovulyatornym cycle in premenopauznom period thiazolidinedione treatment, including drug Aktos may cause ovulation. The consequence of greater sensitivity to insulin in these patients is the risk of pregnancy, unless you use adequate contraception. Clinical studies using the drug Aktos in a dose of 30 mg / day in combination with other hypoglycemic funds were not conducted. Data on the use of the drug Aktos in combination with other drugs thiazolidinediones are not available.
Monitoring of laboratory parameters
Prior to treatment with Aktos, during the first year of treatment (every 2 months) and then periodically monitor the activity of ALT should be.
Use in Pediatrics
Data on the safety and efficacy of the drug Aktos in children and adolescents under the age of 18 years are not available, so the use of the drug Aktos among these patients is not recommended.
Overdose
There was one case of overdosing Aktos (receiving 120 mg / day). It is not mentioned any specific clinical symptoms.
Treatment: symptomatic therapy of conduct depending on the clinical manifestations.
Drug Interactions
Effect Aktos on the effectiveness of contraceptives for oral administration is not known. However, the application of other derivative thiazolidinediones with oral contraceptives was reduced concentrations of ethinyl estradiol and noretindrona in plasma by approximately 30%.
Therefore, patients receiving Aktos and oral contraceptives may decrease the effectiveness of contraception. At the same time taking the drug Aktos (45 mg / day) and glipizida (5 mg / day) for 7 days was not observed changes in the equilibrium state pharmacokinetics glipizida.
Single dose of metformin (1000 mg) on the background of 7-day admission Aktosa a dose of 45 mg / day did not cause changes in the pharmacokinetics of metformin.
At the same time taking the drug Aktos (45 mg / day) and digoxin (0.25 mg / day) for 7 days was not observed changes in the equilibrium state pharmacokinetics of digoxin.
With simultaneous use of the drug Aktos (45 mg / day) and warfarin for 7 days was not observed changes in the equilibrium state pharmacokinetics of warfarin. In addition, Aktos exerted no distinct effect on the prothrombin time in patients who underwent long-term treatment with warfarin.
Ketoconazole inhibits 85% of pioglitazone metabolism in the liver in vitro. Patients receiving ketoconazole simultaneously with the drug Aktos should be conducted more regularly glycemic control.
Terms and Conditions of storage
The drug should be stored at room temperature between 15 ° to 30 ° C in tightly closed containers. Protect from moisture. Shelf life - 3 years.
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