Insulin glargine
Insulin glargine: instructions for use and reviews
- 1. Release form and composition
- 2. Pharmacological properties
- 3. Indications for use
- 4. Contraindications
- 5. Method of application and dosage
- 6. Side effects
- 7. Overdose
- 8. Special instructions
- 9. Application during pregnancy and lactation
- 10. Use in childhood
- 11. In case of impaired renal function
- 12. For violations of liver function
- 13. Use in the elderly
- 14. Drug interactions
- 15. Analogs
- 16. Terms and conditions of storage
- 17. Terms of dispensing from pharmacies
- 18. Reviews
- 19. Price in pharmacies
Latin name: Insulin glargine
ATX code: A10AE04
Active ingredient: insulin glargine (Insulin glargine)
Producer: LLC Endogenics (Russia), Gan & Lee Fharmaceutical (China)
Description and photo update: 2019-11-07
Insulin glargine is a hypoglycemic drug, a long-acting insulin analogue.
Release form and composition
The drug is available in the form of a solution for subcutaneous (s / c) administration: clear colorless liquid (3 ml each in glass transparent cartridges without color, 1 or 5 cartridges in blister strip packs, in a cardboard box 1 package; 10 ml each in glass transparent vials without color, in a cardboard box 1 bottle and instructions for the use of Insulin glargine).
1 ml of solution contains:
- active substance: insulin glargine - 100 units (unit of action), which is equivalent to 3.64 mg;
- auxiliary components: zinc chloride, metacresol, glycerol, sodium hydroxide, hydrochloric acid, water for injection.
Pharmacological properties
Pharmacodynamics
Insulin glargine is a hypoglycemic drug, a long-acting insulin analog.
The active ingredient of the drug is insulin glargine, an analogue of human insulin, obtained by recombination of DNA (deoxyribonucleic acid) of K12 strains of Escherichia coli bacteria.
Insulin glargine is characterized by low solubility in a neutral medium. Full solubility of the active substance in the composition of the drug is achieved due to the content of hydrochloric acid and sodium hydroxide. Their amount provides the solution with an acidic reaction - pH (acidity) 4, which, after the introduction of the drug into the subcutaneous fat, is neutralized. As a result, micro-precipitates are formed, from which there is a constant release of small amounts of insulin glargine, which provides the drug with a prolonged action and a smooth, predictable concentration-time profile.
The kinetics of binding of insulin glargine and its active metabolites M1 and M2 with specific insulin receptors is close to that of human insulin, which determines the ability of insulin glargine to have a biological effect similar to endogenous insulin.
The main action of insulin glargine is the regulation of glucose metabolism. By inhibiting the synthesis of glucose in the liver and stimulating the absorption of glucose by adipose tissue, skeletal muscle and other peripheral tissues, it helps to reduce the concentration of glucose in the blood. Suppresses lipolysis in adipocytes and delays proteolysis, while increasing protein production.
The prolonged action of insulin glargine is due to a reduced rate of its absorption. The average duration of action of insulin glargine after subcutaneous administration is 24 hours, the maximum is 29 hours. The drug takes effect approximately 1 hour after administration. It should be borne in mind that the period of action of insulin glargine in different patients or in one patient can vary significantly.
The effectiveness of the use of the drug in children with type 1 diabetes mellitus over the age of 2 years has been confirmed. With the use of insulin glargine, there is a lower incidence of clinical manifestations of hypoglycemia during the day and at night in children 2–6 years old compared with insulin-isophane.
The results of a 5-year study indicate that in patients with type 2 diabetes mellitus, the use of insulin glargine or insulin-isophane has the same effect on the progression of diabetic retinopathy.
Compared with human insulin, the affinity of insulin glargine for the IGF-1 receptor (insulin-like growth factor 1) is approximately 5–8 times higher, and the active metabolites M1 and M2 are slightly lower.
In patients with type 1 diabetes mellitus, the total concentration of insulin glargine and its metabolites is significantly lower than the level required for half-maximal binding to IGF-1 receptors, followed by activation of the mitogenic-proliferative pathway, which is triggered through IGF-1 receptors. In contrast to the physiological concentrations of endogenous IGF-1, the therapeutic insulin concentration achieved with insulin glargine treatment is significantly lower than the pharmacological concentration sufficient to activate the mitogen-proliferative pathway.
The results of a clinical study indicate that patients with a high risk of cardiovascular disease and impaired glucose tolerance, impaired fasting glycemia, or early-stage type 2 diabetes mellitus with insulin glargine have a comparable likelihood of developing cardiovascular complications or cardiovascular mortality. with that when using standard hypoglycemic therapy. No differences were found in the scores for any component constituting the endpoints, combined scores for microvascular outcomes, and all-cause mortality.
Pharmacokinetics
Compared with insulin-isophane, after subcutaneous administration of insulin glargine, a slower and longer absorption is observed, there is no peak concentration.
Against the background of a single daily subcutaneous injection of Insulin glargine, the equilibrium concentration of the active substance in the blood is reached after 2–4 days.
The half-life (T 1/2) of insulin glargine after intravenous administration is comparable to the T 1/2 of human insulin.
When the drug was injected into the abdomen, thigh or shoulder, no significant differences in serum insulin concentrations were found.
Insulin glargine exhibits less variability in the pharmacokinetic profile in the same patient or in different patients compared with human insulin of average duration.
After the introduction of insulin glargine into the subcutaneous fat, partial cleavage occurs from the carboxyl end (C-end) of the β-chain (beta-chain) with the formation of two active metabolites: M1 (21 A -Gly-insulin) and M2 (21 A - Gly-des-30 B- Тhr-insulin). The metabolite M1 is predominantly circulating in the blood plasma; its systemic exposure increases with an increase in the dose of the drug. Insulin glargine acts primarily through systemic exposure to the M1 metabolite. In the overwhelming majority of cases, it is not possible to detect insulin glargine and the M2 metabolite in the systemic circulation. In rare cases of insulin glargine and M2 metabolite detection in blood, the concentration of each of them did not depend on the administered dose of the drug.
The effect of the patient's age and sex on the pharmacokinetics of insulin glargine has not been established.
Analysis of the results of clinical trials by subgroup showed no difference in the safety and effectiveness of insulin glargine for smokers compared with the general population.
In obese patients, the safety and efficacy of the drug are not impaired.
The pharmacokinetic parameters of insulin glargine in children aged 2 to 6 years with type 1 diabetes mellitus are similar to those in adults.
In severe liver failure, insulin biotransformation slows down due to a decrease in the liver's ability to gluconeogenesis.
Indications for use
The use of Insulin glargine is indicated for patients with diabetes mellitus over the age of 2 years when insulin treatment is required.
Contraindications
Absolute:
- age up to 2 years;
- hypersensitivity to the components of the drug.
Insulin glargine should be used with caution in patients with proliferative retinopathy, severe stenosis of the coronary arteries or cerebral vessels, during pregnancy and breastfeeding.
Insulin glargine, instructions for use: method and dosage
Insulin glargine must not be administered intravenously (IV)!
The solution is intended for subcutaneous injection into the subcutaneous fatty tissue of the abdomen, thighs or shoulders. The injection sites should be rotated within one of the recommended areas.
Resuspension of the drug is not required before use.
If necessary, insulin glargine can be removed from the cartridge into a sterile syringe suitable for insulin and the desired dose of the drug can be injected.
The cartridges can be used with EndoPen pen syringes.
The drug must not be mixed with other insulins!
The dose, the time of administration of the hypoglycemic drug and the target value of the blood glucose concentration are determined and adjusted by the doctor individually.
The effect of changes in the patient's condition, including physical activity, on the degree of absorption, the onset and duration of the drug should be taken into account.
Insulin glargine should be administered subcutaneously once a day, always at the same time, convenient for the patient.
All patients with diabetes should be monitored regularly for blood glucose levels.
In patients with type 2 diabetes mellitus, insulin glargine can be used as monotherapy and in combination with other hypoglycemic agents.
Insulin dose adjustment should be done with caution and under medical supervision. A dose change may be required with a decrease or increase in the patient's body weight, a change in the time of administration of the drug, his lifestyle and other conditions that increase the predisposition to the development of hyper- or hypoglycemia.
Insulin glargine is not the drug of choice for diabetic ketoacidosis, which is treated with short-acting IV insulin.
If the treatment regimen includes injections of basal and prandial insulin, then the dose of insulin glargine that meets the need for basal insulin should be in the range of 40-60% of the daily dose of insulin.
In patients with type 2 diabetes mellitus, who are on therapy with oral forms of hypoglycemic agents, combined treatment should be started with a dose of 10 IU of insulin 1 time per day, followed by individual correction of the treatment regimen.
If the previous treatment regimen included medium-acting or long-acting insulin, then when switching the patient to the use of insulin glargine, it may be necessary to change the dose and time of administration of short-acting insulin (or its analogue) during the day or adjust the dose of oral hypoglycemic agents.
When transferring a patient from the administration of the dosage form of insulin glargine, containing 300 U in 1 ml, to the administration of insulin glargine, the initial dose of the drug should be 80% of the dose of the previous drug, the use of which is discontinued, and also administered once a day. This will reduce the risk of hypoglycemia.
When switching from the introduction of insulin-isophane once a day, the initial dose of insulin glargine usually does not change and is administered once a day.
When switching from the introduction of insulin-isophane 2 times a day to a single dose of insulin glargine before bedtime, it is recommended to reduce the initial daily dose of the drug by 20% of the previous daily dose of insulin-isophane. The following shows its correction depending on the individual reaction.
Insulin glargine should be started after prior human insulin therapy only under close medical supervision, including monitoring blood glucose concentrations. During the first weeks, if necessary, the dosage regimen is adjusted. This is especially true for patients with anti-human insulin antibodies who require high doses of human insulin. Their use of insulin glargine, which is an analogue of human insulin, can significantly improve the response to insulin.
With an increase in tissue sensitivity to insulin due to improved metabolic control, correction of the dosage regimen is possible.
In elderly patients with diabetes mellitus, it is recommended to use moderate initial and maintenance doses of insulin glargine and slowly increase them. It should be borne in mind that in old age, the recognition of developing hypoglycemia is difficult.
Side effects
Adverse events from systems and organs (classified as follows: very often -> 10%; often -> 1% and 0.1% and 0.01% and <0.1%; very rarely - <0.01%, including isolated cases):
- on the part of metabolism and nutrition: very often - hypoglycemia;
- on the part of the immune system: rarely - allergic reactions [including generalized skin reactions, angioedema, bronchospasm, lowering blood pressure (BP), shock, including with a threat to the patient's life], the formation of antibodies to insulin;
- from the nervous system: very rarely - violation or perversion of taste sensations (dysgeusia);
- on the part of the organ of vision: rarely - temporary visual impairment, retinopathy (including with transient loss of vision);
- from the skin and subcutaneous tissues: often - lipodystrophy; infrequently - lipoatrophy;
- from the musculoskeletal system: very rarely - myalgia;
- general disorders and disorders at the injection site: often - reactions at the injection sites in the form of pain, itching, redness, edema, urticaria or inflammation; rarely - edema (more often with effective intensified insulin therapy), sodium retention.
Overdose
Overdose usually causes sudden onset of symptoms characteristic of severe hypoglycemia. Often its appearance is preceded by symptoms of adrenergic counterregulation associated with activation of the sympathoadrenal system in response to hypoglycemia. They are characterized by a feeling of hunger and anxiety, irritability, pallor of the skin, tremors or nervous excitement, cold sweat, palpitations, tachycardia. The severity of the symptoms of adrenergic counterregulation is the stronger, the more rapid the development of hypoglycemia and the more severe it is. Against the background of neuroglycopenia, the patient develops the following neuropsychiatric disorders: drowsiness, fatigue, weakness, unusual fatigue, decreased ability to concentrate, visual disturbances, nausea, headache, confusion, loss of consciousness,convulsive syndrome.
To stop episodes of moderate hypoglycemia, immediate ingestion of easily digestible carbohydrates is usually sufficient. If necessary, make a change in the dosage regimen, diet or physical activity. When seizures, neurological disorders, coma appear, intramuscular (i / m) or s / c administration of glucagon and i / v administration of a concentrated glucose solution (dextrose) are required. The patient needs close supervision of a specialist and long-term intake of carbohydrates. It should be borne in mind that a visible clinical improvement may be followed by a relapse of hypoglycemia.
special instructions
The efficacy and safety of the use of Insulin glargine in patients with impaired liver function or with moderate or severe renal failure have not been established. It is assumed that due to the slowdown in the elimination of insulin with impaired renal function, its need may decrease. Consideration should be given to the progressive deterioration of renal function in elderly patients, contributing to a sustained trend towards a decrease in insulin requirements.
If there is insufficient glycemic control or there is a tendency to develop hypo- or hyperglycemia, correction of the dosage regimen should be carried out only after careful verification of the patient's accuracy of the prescribed treatment regimen. In addition, other factors affecting blood glucose concentration should be considered, including adherence to injection sites and correct subcutaneous injection technique.
Hypoglycemia is the most frequent undesirable effect of insulin therapy; it can occur when the dose of insulin and the need for it do not match, including when changing the treatment regimen. It should be borne in mind that against the background of the use of Insulin glargine, the likelihood of developing nocturnal hypoglycemia is less than in the early morning hours. In addition, due to the prolonged action of the drug, it is possible to slow down the recovery from hypoglycemia. In patients with severe stenosis of the coronary arteries or cerebral vessels, episodes of hypoglycemia may contribute to a clinically significant increase in the risk of developing cardiac and cerebral complications of hypoglycemia. Particular caution is also recommended in patients with proliferative retinopathy, especially in the absence of photocoagulation treatment. In this category of patients, against the background of hypoglycemia, the likelihood of transient vision loss increases. Therefore, those at high risk should be warned about the need for intensive monitoring of blood glucose concentration.
Recurrent episodes of severe hypoglycemia can damage the nervous system, and prolonged and severe episodes can be life-threatening.
When prescribing the drug, the doctor should pay special attention to the patient that in some conditions the symptoms-precursors of hypoglycemia may become less pronounced or completely absent. Changes in symptoms can occur in cases of transition from treatment with animal insulin to human insulin, with the gradual development of hypoglycemia, a long history of diabetes mellitus, a significant improvement in glycemic regulation, autonomic neuropathy, the presence of mental disorders, concomitant therapy with other drugs that enhance the hypoglycemic effect of insulin, and / or in the elderly patient.
Mild hypoglycemic precursor symptoms are very dangerous for patients due to the high risk of developing a severe form of hypoglycemia (including loss of consciousness) before the patient realizes it.
With normal or decreased levels of glycated hemoglobin, it is necessary to take into account the increase, especially at night, in the risk of developing recurrent unrecognized episodes of hypoglycemia.
The tendency to hypoglycemia increases in the presence of the following factors: a change in the place of insulin injection, a violation of the diet and diet, an increase in insulin sensitivity (including when eliminating stress factors), increased, prolonged or unusual physical activity, intercurrent pathologies accompanied by vomiting and / or diarrhea, alcohol consumption, uncompensated endocrine disorders - hypothyroidism, insufficiency of the adrenal cortex or adenohypophysis, the simultaneous use of other drugs.
The emergence of intercurrent diseases requires more intensive monitoring of blood glucose levels. Often there is a need to conduct an analysis for the presence of ketone bodies in the urine, adjust the dosage regimen of insulin (in many cases, to increase the dose). Patients with type 1 diabetes should not stop insulin administration. Their diet should include regular low carbohydrate intake, even when their diet is limited to small amounts of food, or lacking the ability to eat, including vomiting.
Influence on the ability to drive vehicles and complex mechanisms
During the period of use of Insulin glargine, when driving vehicles and complex mechanisms, patients should take into account the increased risk of disorders that affect concentration and the speed of psychomotor reactions caused by visual impairment, the development of conditions such as hyperglycemia or hypoglycemia.
Application during pregnancy and lactation
The use of Insulin glargine during gestation and during breastfeeding is allowed for clinical reasons. Patients are advised to be careful due to the fact that there may be a need to change the dose of insulin during pregnancy or after childbirth.
When planning a pregnancy or conception, you must inform your doctor.
The use of insulin glargine during pregnancy is not accompanied by specific effects that affect its course and labor or the condition of the fetus and the health of the newborn.
The results of observational clinical studies on the use of insulin glargine and insulin-isophane during pregnancy in women with pre-existing or gestational diabetes mellitus indicate that there are no significant differences in terms of safety, both in terms of maternal and newborn health. It is recommended for this category of patients to maintain adequate regulation of metabolic processes during the entire period of gestation, preventing the occurrence of undesirable outcomes associated with hyperglycemia.
It should be borne in mind that in the first trimester of pregnancy there may be a need to lower the dose of insulin, and during the second and third trimesters - to increase it.
Immediately after childbirth, the risk of hypoglycemia increases due to the rapid decrease in insulin requirements. Therefore, patients need careful monitoring of blood glucose concentrations.
During lactation, consideration should be given to the need to correct diet and insulin dosing regimen.
Pediatric use
The use of Insulin glargine is contraindicated in children under 2 years of age.
The safety profile in children 2 to 18 years of age is similar to that of patients over 18 years of age.
Children are more likely to experience adverse reactions at the injection site, skin rashes and hives.
With impaired renal function
In case of impaired renal function, the need for insulin glargine may decrease, it is necessary to control the concentration of glucose in the blood.
For violations of liver function
In severe hepatic impairment, it is recommended to lower the dose of insulin glargine.
Use in the elderly
In older patients, it is difficult to recognize the symptoms of hypoglycemia.
With a progressive deterioration in renal function, it is necessary to carefully monitor the level of glycemia in connection with a steady trend towards a decrease in insulin requirements.
Drug interactions
- oral hypoglycemic agents, monoamine oxidase inhibitors, angiotensin-converting enzyme inhibitors, salicylates, sulfonamide antimicrobial agents, fibrates, disopyramide, fluoxetine, pentoxifylline, propoxyfene: may increase the hypoglycemic effect of insoglycemia, increasing the risk of hypoglycemic effects of insoglycemia;
- glucagon, glucocorticosteroids, diuretics, phenothiazine derivatives, protease inhibitors, isoniazid, danazol, diazoxide, estrogens and gestagens (including hormonal contraceptives), somatropin, sympathomimetics (including epinephrine, adrenaline, terbutaline, salbutamines of the thyroid gland), clozapine): reduce the hypoglycemic action of insulin glargine;
- beta-blockers, lithium salts, clonidine, ethanol (alcohol): can potentiate or weaken the hypoglycemic effect of insulin;
- pentamidine: may contribute to the development of hypoglycemia, sometimes alternating with hyperglycemia;
- sympatholytics, including beta-blockers, guanethidine, reserpine, clonidine: concomitant therapy with drugs with sympatholytic activity can reduce or hide the symptoms of adrenergic counterregulation (activation of the sympathetic nervous system) when hypoglycemia occurs.
Mixing insulin glargine with other insulins or drugs can change its profile of action or lead to precipitation.
Analogs
Insulin glargine analogs are Lantus SoloStar, Tujeo SoloStar.
Terms and conditions of storage
Keep out of the reach of children.
Store at 2–8 ° C, keep away from freezing.
Shelf life is 2 years.
Terms of dispensing from pharmacies
Dispensed by prescription.
Reviews about insulin glargine
There are no reviews of Insulin glargine.
The price of Insulin glargine in pharmacies
The price of Insulin glargine has not been established due to the lack of the drug in pharmacies. The cost of analogs: Lantus SoloStar - 849 or 4167 rubles. (for 1 or 5 cartridges, respectively); Tudgeo SoloStar - 992, 3115 or 4510 rubles. (for 1, 3 or 5 cartridges, respectively).
Anna Kozlova Medical journalist About the author
Education: Rostov State Medical University, specialty "General Medicine".
Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!
