Instruction for use: ApidraI want this, give me price
Active substance Insulin glulisine
ATX codeA10AB06 Insulin glulisine
Pharmacological group of substance Calcitonin
Nosological classification (ICD-10)
E10 Insulin-dependent diabetes mellitus
Decompensation of carbohydrate metabolism, Diabetes mellitus, Diabetes insulin sugar, Diabetes mellitus type 1, Diabetic ketoacidosis, Insulin-dependent diabetes, Insulin-dependent diabetes mellitus, Coma hyperosmolar non-ketoacidotic, Labile form of diabetes mellitus, Violation of carbohydrate metabolism, Type 1 diabetes mellitus, Type I diabetes mellitus, Insulin-dependent diabetes mellitus, Type 1 diabetes mellitus
Composition and form of release
Solution for subcutaneous administration 1 ml
Insulin glulisine 3.49 mg
(Corresponding to 100 IU of human insulin)
Excipients: m-cresol; Trometamol; sodium chloride; Polysorbate 20; Sodium hydroxide; Hydrochloric acid concentrated; water for injections
In bottles of 10 ml or in cartridges of 3 ml; In a pack of cardboard 1 bottle or in a contour acheikova pack 5 cartridges for the syringe-pen "Optifen" or cartridges mounted in a disposable syringe-handle "Optiset" or with the cartridge system "OptikKlik".
Description of dosage form
Transparent, colorless or almost colorless liquid.
Pharmacological action - hypoglycemic.
Insulin glulisin is a recombinant analog of human insulin, which by force of action is equal to the normal human insulin. Insulin glulisin starts to act faster and has a shorter duration of action than soluble human insulin. The most important action of insulin and insulin analogues, including insulin glulisin, is the regulation of glucose metabolism. Insulin reduces the concentration of glucose in the blood, stimulating the absorption of glucose by peripheral tissues, especially skeletal muscle and fat tissue, and also inhibiting the formation of glucose in the liver. Insulin inhibits lipolysis in adipocytes and proteolysis and increases protein synthesis. Studies conducted in healthy volunteers and patients with diabetes mellitus have shown that when insulin is injected with insulin glulisin begins to act faster and has a shorter duration of action than soluble human insulin. With n / to the introduction of lowering blood glucose in the blood, the effect of glulisin insulin begins in 10-20 minutes. With intravenous administration, the effects of lowering blood glucose in the blood of insulin glulisin and soluble human insulin are equal in strength. One unit of glulisin insulin has the same glucose-lowering activity as one unit of soluble human insulin.
In the Phase I study, patients with type 1 diabetes mellitus were assessed for glucose-lowering profiles of glulisin insulin and soluble human insulin administered at a dose of 0.15 U / kg SC at different times with respect to the standard 15-minute meal.
The results of the study showed that insulin glulisine, administered 2 minutes before a meal, provided the same glycemic control after meals as the soluble human insulin administered 30 minutes before meals. When administered 2 minutes before meals, insulin glulisin provided better glycemic control after eating than soluble human insulin administered 2 minutes before meals. Insulin glulisine, administered 15 minutes after the start of food intake, gave the same glycemic control after meals as the soluble human insulin administered 2 minutes before meals.
Obesity. Phase I study, conducted with insulin glulisin, insulin lispro and soluble human insulin in a group of obese patients, demonstrated that in these patients, insulin glulisin retained its fast-acting characteristics. In this study, the time to reach 20% of the total AUC was 114 min - for glulisin insulin, 121 min for insulin lispro and 150 min for soluble human insulin, and AUC (0-2 hours), reflecting also early glucose-lowering activity, was 427 Mg · kg-1 for insulin glulisin, 354 mg · kg-1 for insulin lispro and 197 mg · kg-1 for soluble human insulin, respectively.
Type 1 diabetes mellitus. In a 26-week phase III clinical trial comparing insulin glulisin with insulin lispro administered shortly before meals (0-15 min) in patients with type 1 diabetes using basal insulin Insulin glargine, insulin glulisin was comparable to insulin lyspro for glycemic control, which was estimated from a change in the concentration of glycosylated hemoglobin (HbA1C) at the endpoint of the study compared to the outcome. Comparable values of blood glucose, determined by self-monitoring, were observed. With the introduction of insulin glulisin, unlike the treatment with insulin, lyspro did not require an increase in the dose of basal insulin.
A 12-week Phase III clinical trial in patients with type 1 diabetes treated as basal insulin glargine showed that the effectiveness of insulin glulisin immediately after meals was comparable to that of glulisin insulin just before meals (0 -15 min) or soluble human insulin (30-45 minutes before meals).
In a population of patients who completed the study protocol, a significantly greater decrease in HbA1C was observed in the group of patients who received pre-meal insulin glulisin compared to the group of patients receiving soluble human insulin.
Type 2 diabetes mellitus. A 26-week phase III clinical trial followed by a 26-week follow-up as a safety study was conducted to compare glulisin insulin (0-15 min before meals) with soluble human insulin (30-45 Min before meals), which were given SC in patients with type 2 diabetes mellitus, besides using basal insulin-isophane as a basal insulin. The average body mass index of patients was 34.55 kg / m2. Insulin glulisin showed itself comparable to soluble human insulin for changes in HbA1C concentrations after 6 months of treatment compared to the outcome (-0.46% for glulisin insulin and -0.30% for soluble human insulin, p = 0.0029) and through 12 months of treatment compared with the outcome (-0.23% for insulin glulisin and -0.13% for soluble human insulin, the difference is not reliable). In this study, most patients (79%) mixed their short-acting insulin with insulin-isophane immediately before injection. At the time of randomisation, 58 patients used oral hypoglycemic drugs and received instructions to continue their use at the same dose.
Racial origin and sex. In controlled clinical studies in adults, there was no difference in the safety and efficacy of glulisin insulin in the analysis of subgroups distinguished by race and sex.
In insulin glulisine, the substitution of the amino acid asparagine of human insulin at position B3 for lysine and lysine at position B29 for glutamic acid facilitates faster absorption.
Absorption and bioavailability. The pharmacokinetic concentration-time curves in healthy volunteers and patients with type 1 and type 2 diabetes demonstrated that the absorption of glulisin insulin compared to soluble human insulin was approximately 2 times faster, reaching up to twice the C max.
In a study conducted in patients with type 1 diabetes mellitus, after glucosin insulin administration at a dose of 0.15 U / kg Tmax (the onset time of Cmax) was 55 min and Cmax in blood plasma was (82 ± 1.3) μed / Ml compared to Tmax of 82 min and Cmax of (46 ± 1.3) μed / ml for soluble human insulin. The mean residence time in the systemic circulation of glulisin insulin was shorter (98 min) than for normal human insulin (161 min).
In a study in patients with type 2 diabetes mellitus, after glucosin insulin administration at a dose of 0.2 U / kg C max was 91 μed / ml with interquartile latitude from 78 to 104 μed / ml.
With n / to the introduction of glulisin insulin into the anterior abdominal wall, thigh or shoulder (deltoid muscle region), absorption was faster when inserted into the anterior abdominal wall as compared with the introduction of the drug into the thigh. The rate of absorption from the deltoid muscle region was intermediate. The absolute bioavailability of glulisin insulin (70%) at different sites of administration was similar and had low variability between different patients. The coefficient of variation (CV) is 11%.
Distribution and elimination. The distribution and excretion of insulin glulisin and soluble human insulin after iv administration are similar, with distribution volumes of 13 and 22 liters and T1 / 2 of 13 and 18 minutes, respectively.
After insulin administration, glulisin is excreted faster than soluble human insulin, having an apparent T1 / 2 of 42 minutes, compared to the apparent T1 / 2 soluble human insulin of 86 minutes. In a cross-sectional analysis of studies of insulin glulisin, both in healthy individuals and in individuals with type 1 and type 2 diabetes, the apparent T1 / 2 was in the range of 37 to 75 minutes.
Special patient groups
Renal insufficiency. In a clinical study conducted in individuals without diabetes mellitus with a wide range of renal functional status (Cl creatinine> 80 ml / min, 30-50 ml / min, <30 ml / min), the overall rapidity of the insulin glulisin effect persisted. However, the need for insulin in the presence of renal insufficiency can be reduced.
Liver failure. In patients with impaired hepatic function, pharmacokinetic parameters were not studied.
The elderly. There are very limited data on the pharmacokinetics of insulin glulisin in elderly patients with diabetes mellitus.
Children and teenagers. Pharmacokinetic and pharmacodynamic properties of glulisin insulin have been studied in children (7-11 years old) and adolescents (12-16 years old) with type 1 diabetes mellitus. In both age groups, glulisin is rapidly absorbed with Tmax and Cmax, similar to those in adults. Like adults, when administered directly before a meal test, insulin glulisin provides better control of blood glucose after eating than soluble human insulin. The increase in blood glucose after meal (AUC 0-6 h - the area under the curve of blood glucose concentration - time from 0 to 6 h) was 641 mg · h · dl-1 for insulin glulisin and 801 mg · h · Dl-1 for soluble human insulin.
Diabetes mellitus, requiring insulin treatment, in adults, adolescents and children over 6 years of age.
Hypersensitivity to insulin glulisin or to any of the components of the drug;
Caution should be used in pregnant women.
pregnancy and lactation
Pregnancy. There is insufficient information on the use of glulisin insulin in pregnant women.
Animal reproduction studies did not reveal any difference between insulin glulisin and human insulin with respect to pregnancy, embryonic / fetal development, childbirth and postnatal development.
When prescribing the drug, pregnant women should be careful. A thorough monitoring of the blood glucose level is mandatory.
Patients with pre-pregnancy or gestational diabetes mellitus need to maintain optimal metabolic control throughout pregnancy. During the first trimester of pregnancy, the need for insulin may decrease, and during the second and third trimesters, it can usually increase. Immediately after delivery, the need for insulin rapidly decreases.
Lactation. It is not known whether insulin glulisin enters the female milk, but in general insulin does not penetrate into the female milk and is not absorbed when ingested.
Breastfeeding mothers may need to adjust their insulin doses and diet.
Hypoglycemia, the most frequent undesirable effect of insulin therapy, can occur if too high doses of insulin are used, exceeding the need for it.
The following adverse reactions associated with the administration of the drug in clinical trials are listed below for organ systems and in order of decreasing incidence: very often -> 1/10; Often -> 1/100, <1/10; Sometimes -> 1/1000, <1/100; Rarely -> 1/10000, <1/1000; Very rarely - <1/10000.
Metabolic disorders: very often - hypoglycemia.
Symptoms of hypoglycemia usually develop suddenly. These include: the appearance of cold sweat, pallor and coolness of the skin, a feeling of fatigue, nervous excitement or tremor, anxiety, unusual fatigue or weakness, confusion, difficulty concentrating, drowsiness, excessive hunger, visual disturbances, headache, nausea and severe Palpitation. Hypoglycemia can build up, which can lead to loss of consciousness and / or the appearance of seizures, as well as temporary or permanent impairment of brain function or even death.
Disturbances from the skin and subcutaneous tissues: often - reactions at the injection site and local hypersensitivity reactions (congestion, swelling and itching at the injection site). These reactions are usually transient, and normally disappear as they continue treatment. Rarely, lipodystrophy.
As a result of the violation of the alternation of places of insulin administration in one of the regions (administration of the drug to the same place), the development of lipodystrophy is possible at the site of administration.
Common disorders: not often - systemic hypersensitivity reactions.
Systemic hypersensitivity reactions can manifest in the form of urticaria, feelings of tightness in the chest, suffocation, allergic dermatitis and itching. Severe cases of generalized allergies, including anaphylactic reactions, can be life threatening.
Studies on pharmacokinetic interactions were not conducted. Based on the available empirical knowledge of other similar drugs, the occurrence of clinically significant pharmacokinetic interactions is unlikely. Some substances can affect glucose metabolism, which may require correction of glulisine insulin doses and especially careful monitoring of treatment.
To substances that can increase the hypoglycemic action of insulin and increase the predisposition to hypoglycemia include: oral hypoglycemic agents, angiotensin converting enzyme inhibitors, disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors, pentoxifylline, propoxyphene, salicylates and sulfonamide antimicrobials.
To substances that can reduce the hypoglycemic action of insulin, include: GCS, danazol, diazoxide, diuretics, isoniazid, phenothiazine derivatives, somatropin, sympathomimetics (eg epinephrine (adrenaline), salbutamol, terbutaline), thyroid hormones, estrogens, progestins (eg in oral Contraceptive agents), protease inhibitors and antipsychotic drugs (eg olanzapine and clozapine).
Beta-adrenoblockers, clonidine, lithium salts or alcohol can either potentiate or weaken the hypoglycemic effect of insulin. Pentamidine may cause hypoglycemia with subsequent hyperglycaemia.
In addition, under the influence of such drugs with sympatholytic activity, like beta adrenoblockers, clonidine, guanethidine and reserpine, symptoms of reflex adrenergic activation may be less pronounced or absent.
Due to the lack of compatibility studies, insulin glulisin should not be mixed with any other drugs except for human insulin isophane.
When administered with an infusion pump, Apidra® should not be mixed with other drugs.
Dosing and Administration
P / to, shortly before (for 0-15 minutes) or soon after meal.
The drug Apidra® should be used in treatment regimens that include either medium-term insulin or long-acting insulin or a long-acting insulin analogue, as well as in combination with oral hypoglycemic agents.
Dosing regimen of the drug Apidra® is selected individually.
Administration of the drug
Preparation of Apidra® by injection or by continuous infusion into the subcutaneous fat with the aid of a pump system.
S / injection should be made in the abdomen, shoulder or thigh, and the introduction of the drug by continuous infusion into the subcutaneous fat is produced in the abdomen. The injection site and the infusion site in the above areas (abdomen, hip or shoulder) should alternate with each new administration of the drug. The absorption rate and, accordingly, the beginning and duration of the action can be influenced by: the site of injection, physical stress and other changing conditions.
A / c injection into the abdominal wall provides for a somewhat faster absorption than the introduction into the other abovementioned parts of the body.
Precautions should be taken to ensure that the drug does not enter the blood vessels directly. After the administration of the drug, massage of the area of administration can not be performed. Patients should be trained in proper injection techniques.
Mixing with insulin. The drug Apidra® should not be mixed with any other drug than human insulin-isophane.
Pump device for continuous subcutaneous infusion
When using Apidra® with a pump system for insulin infusion, it should not be mixed with other drugs. For further information on handling the product, see the "Instructions for Use and Handling" section.
It is necessary to strictly follow the instructions for the correct handling of pre-filled syringes (see section "Instructions for use and circulation").
Special groups of patients
Impaired renal function. The need for insulin in renal failure may be reduced.
Violation of the function of the liver. In patients with impaired liver function, the need for insulin may decrease due to reduced ability to gluconeogenesis and slowing down the metabolism of insulin.
Sick of the elderly. The available data on the pharmacokinetics in elderly patients with diabetes mellitus are inadequate. Violation of kidney function in old age can lead to a decrease in the need for insulin.
Children and teenagers. The drug can be used in children older than 6 years and adolescents. Clinical information on the use of the drug in children younger than 6 years is limited.
Instructions for use and circulation
Since the Apidra® preparation is a solution, no resuspension is required before use.
Mixing with insulin. When mixed with human insulin-isophane, the Apidra® preparation must be syringed first. Injection should be carried out immediately after mixing, because There is no data on mixtures prepared long before injection.
Bottles. The drug Apidra® in vials is intended for use with insulin syringes with a corresponding scale of units and for use with a pump insulin system.
Before use, inspect the bottle. It should only be used if the solution is clear, colorless and free from visible solids.
Continuous infusion of infusion with a pump system. Apidra® can be used to perform continuous insulin infusion (NPII) using a pump system suitable for insulin infusion with appropriate catheters and reservoirs.
Infusion set and reservoir should be replaced every 48 hours with the implementation of aseptic rules.
Patients receiving Apidra® by NPII should have an alternative insulin in reserve in case of failure of the pump system.
Pre-filled syringe pens OptiSet. Before use, inspect the cartridge inside the syringe pen. It should only be used if the solution is clear, colorless, free of visible solids and has a consistency similar to water.
Never use an empty syringe "OptiSet", it should be discarded.
To prevent any type of infection, a pre-filled syringe pen should only be used by strictly one patient.
Handling of the syringe-handle "Optiset". Before using the OptiSet syringe pen, carefully read the insert leaflet with the instructions for use.
Important information on the use of the OptiSet pen. Before using, you must firmly connect the new needle to the syringe pen and check its readiness for use. Never rotate the dispenser after setting the dispenser button to the "released" position.
If there are problems with the syringe handle "OptiSet", refer to the "Troubleshooting" section of the user manual.
If the OptiSet syringe is defective, it can not be used.
General instructions. The button of the insulin dispenser allows you to check the dose actually prepared for administration: when the button is in the "pressed" position, the last visible thick dash (only its upper part can be seen) shows the amount of insulin prepared for administration. If the dash is seen badly, then it can be seen better by holding the syringe handle at an angle.
Insulin syringe pen can not be dropped on the floor or struck on it (otherwise, the insulin cartridge located in the transparent insulin tank can break and the syringe pen will not work). If this happens, then a new syringe pen should be used.
Insulin testing. After removing the cap from the syringe pen, the labeling on the insulin tank must be checked to make sure it contains the proper insulin. You should also check the appearance of insulin: the insulin solution should be clear, colorless, free of visible solids and have a consistency similar to water.
Attaching the needle. Only those needles that are approved for use with the OptiSet syringe can be used. After removing the cap from the syringe-pen, you should carefully attach the needle to the syringe pen.
Check whether the syringe is ready for use. Before each injection, the syringe-pen must be checked for use.
For a new and unused syringe-pen, the dose indicator should stand in front of the figure 8, as was previously set by the manufacturer. In other cases, the dispenser should be turned until the dose indicator stops in front of the digit 2. After this, the dispenser button must be pressed all the way to the stop.
Remove the outer and inner needle caps.
Holding the syringe handle with the needle pointing upwards, gently tap with your finger on the insulin reservoir so that the air bubbles go up towards the needle. After this, press the dispenser button until it stops.
If a drop of insulin is released from the tip of the needle, the syringe-pen and the needle function correctly.
If the insulin solution does not show up from the tip of the needle, repeat this step until the insulin solution appears from the tip of the needle.
Installation and charging of the syringe pen with a dose of insulin. A dose of 2 units up to 40 units can be set in 2-step increments. If a dose greater than 40 is required, it should be given in two or more injections.
The dispenser should be rotated in any direction until the dose indicator stops in front of the required dose.
To recharge the syringe handle, the dispenser button should be pulled as far as it will go.
Introduction of insulin dose. Patients should be instructed by the health care provider regarding injection techniques.
The needle should be inserted into the subcutaneous fat layer.
You must press the dispenser button all the way. Then, before removing the needle, hold the dispenser button in the "pressed" position for 10 seconds.
Removing the needle. After each injection, the needle should be removed from the syringe-pen and discarded. This will prevent infection, as well as leakage of insulin, re-entry of air and possible blockage of the needle. Needles should not be reused.
Check the remaining amount of insulin in the tank. The scale of the remaining insulin on a transparent insulin tank shows how much insulin is approximately left in the OptiSet syringe. This scale should not be used to set a dose of insulin.
The dispenser button allows you to check the dose actually prepared for the introduction: the button should be pressed. While holding it in the "depressed" position, the last visible greasy dash (only its upper part can be seen) shows the amount of insulin prepared for administration. If the dash is seen badly, then it can be seen better by holding the syringe handle at an angle.
In case the patient is not sure that enough insulin remains in the reservoir, the syringe-handle "OptiSet" should be discarded.
Cartridges. Cartridges should be used together with an insulin syringe pen, such as "OptiPen Pro1", and in accordance with the recommendations in the information provided by the device manufacturer.
The manufacturer's instructions for the use of the Optipen Pro1 syringe pen regarding the loading of the cartridge, the attachment of the needle and the injection of insulin must be strictly followed. You should inspect the cartridge before use. It should only be used if the solution is clear, colorless, free of visible solids. Before inserting the cartridge into the reusable syringe pen, the cartridge should be at room temperature for 1-2 hours. Before carrying out the injection, air bubbles should be able to escape from the cartridge (see instructions for using the syringe pen).
Instructions for the use of the syringe handle must be strictly followed. Empty empty cartridges can not be refilled. If the OptiPen Pro1 syringe is damaged, it can not be used.
If the syringe pen does not work correctly, the solution can be recruited from the cartridge into a plastic syringe suitable for insulin at a concentration of 100 IU / ml and administered to the patient.
To prevent infection, the reusable syringe pen should only be used for one patient.
Cartridge system "OpticKlik". The "Optiklik" cartridge system is a glass cartridge containing 3 ml of glulisin insulin solution, which is fixed in a transparent plastic container with an attached piston mechanism.
The "Optiklik" cartridge system should be used together with the "Optiklik" syringe handle in accordance with the recommendations in the information provided by the device manufacturer.
The manufacturer's instructions on the use of the "Optiklik" syringe handle regarding the loading of the cartridge system, the attachment of the needle and the injection of insulin must be precisely followed.
If the syringe handle "Optiklik" is damaged or does not work properly (as a result of a mechanical defect), it must be replaced with a new one.
Before installing the cartridge system in the syringe-handle "Optiklik", it should be at room temperature for 1-2 hours. It is necessary to inspect the cartridge system before installation. It should only be used if the solution is clear, colorless, free of visible solids. Before carrying out the injection, air bubbles should be removed from the cartridge system (see instructions for using the syringe pen). Empty empty cartridges can not be refilled.
If the syringe pen does not work properly, the solution can be recruited from the cartridge system into a plastic syringe suitable for insulin at a concentration of 100 IU / ml and administered to the patient.
To prevent infection, the reusable syringe pen should only be used for one patient.
Symptoms: with an excess of insulin in relation to the need for it, determined by food intake and energy consumption, hypoglycemia may develop.
There are no specific data on glutamine insulin overdose. However, with its overdose, it is possible to develop hypoglycemia in mild or severe form.
Treatment: episodes of mild hypoglycemia can be stopped by taking glucose or foods containing sugar. Therefore, it is recommended that patients with diabetes always have pieces of sugar, sweets, biscuits or sweet fruit juice.
Episodes of severe hypoglycemia, during which the patient loses consciousness, can be stopped intramuscularly or by injection of 0.5-1 mg of glucagon, which is produced by the person who received the appropriate instructions, or / in the introduction of dextrose (glucose) by a medical worker. If the patient does not respond to the administration of glucagon within 10-15 minutes, it is also necessary to administer dextrose IV.
After restoration of consciousness it is recommended to give the patient carbohydrates inside to prevent recurrence of hypoglycemia.
After the introduction of glucagon to establish the cause of this severe hypoglycemia and prevent the development of other similar episodes, the patient should be observed in the hospital.
Transfer of the patient to a new type of insulin or another manufacturer's insulin should be carried out under strict medical supervision, since a change in dosage may be required due to a change in the concentration of insulin, a brand (manufacturer), insulin type (soluble, insulin-isophane, etc.) Insulin (animal origin) and / or mode of production. In addition, correction of concomitant oral hypoglycemic therapy may be required. The use of inadequate insulin doses or discontinuation of treatment, especially in patients with type 1 diabetes, can lead to the development of hyperglycemia and diabetic ketoacidosis - conditions that are potentially life threatening.
Hypoglycemia. The time through which hypoglycemia develops depends on the rate of onset of the effect of the insulin used and, in this connection, can change with a change in the treatment regimen. Conditions that can change or make less pronounced precursors of hypoglycemia include: the long existence of diabetes mellitus, the intensification of insulin therapy, the presence of diabetic neuropathy, the intake of certain medications such as beta-blockers, or the transfer of a patient from animal insulin to human insulin.
Correction of insulin doses may also be required if patients increase physical activity or change their usual eating patterns. Physical exercise performed immediately after a meal can increase the risk of developing hypoglycemia. Compared to soluble human insulin, hypoglycemia may develop earlier after the injection of fast acting insulin analogues.
Uncompensated hypoglycemic or hyperglycaemic reactions can lead to loss of consciousness, coma development or death.
The need for insulin can change with diseases or emotional overload.
Unopened vials, pre-filled OptiSet syringes, OptiKlik cartridges and cartridge systems
At a temperature of 2 ° C to 8 ° C, in a dark place. Do not freeze!
After the start of use. Opened vials, pre-filled OptiSet syringes, OptiKlik cartridges or cartridge systems should be stored at a temperature not exceeding 25 ° C in a place protected from light and out of reach of children.
To protect from exposure to light, you should store the bottle, the pre-filled OptiSet pen, the cartridge or the OptiKlik cartridge system in your own carton.
Pre-filled syringe-pen "Optiset" - do not chill.
Note: the shelf life of the drug in the vial, cartridge, cartridge system "OpticKlik" or syringe-handle "OptSet" after the first use - 4 weeks. It is recommended to mark on the label the date of the first withdrawal of the drug.
Terms of leave from pharmacies
In the dark place at a temperature of 2-8 ° C (do not freeze).
Keep out of the reach of children.
Do not use after the expiry date printed on the package.