Lantus® Solostar®

General characteristics. Structure:

Active agent: insulin гларгин 100 PIECES (3,6378 mg).
Excipients: metacresol (m cresol), zinc chloride, глицерол (85%), sodium hydroxide, Acidum hydrochloricum, water for injections.
Description: transparent, colourless or almost colourless liquid.

Pharmacological properties:

Pharmacodynamics. Insulin гларгин is the analog of human insulin received by method of a recombination of DNA of bacteria of a look Escherichia coli (K12 strains).
Insulin гларгин is developed as the analog of human insulin differing in low solubility in the neutral environment. As a part of the drug Lantus® Solostar® it is completely soluble that is provided with acid reaction of solution for injections (рН 4). After introduction to a hypodermic fatty tissue acid reaction of solution is neutralized that leads to formation of microprecipitated calcium superphosphates from which small amounts of insulin of a glargin are constantly released, providing predictable, smooth (without peaks) a curve profile "concentration time", and also the prolonged effect of drug.
Communication with insulin receptors: the kinetics of linkng with specific receptors of insulin at insulin of a glargin is very close that at human insulin in this connection insulin гларгин is capable to carry out the biological effect similar to that at endogenous insulin.
The most important effect of insulin and its analogs including insulin of a glargin, glucose metabolism regulation is. Insulin and its analogs reduce the content of glucose in blood, stimulating glucose absorption with peripheral fabrics (especially skeletal muscles and fatty tissue) and inhibiting formation of glucose in a liver. Insulin suppresses a lipolysis in adipocytes and inhibits proteolysis, increasing at the same time protein synthesis.
The prolonged effect of insulin of a glargin directly is connected with the reduced speed of its absorption that allows to use drug once a day. After hypodermic introduction the beginning of its action comes, on average, in 1 hour. The average duration of action makes 24 hours, maximum - 29 hours. Duration of effect of insulin and its analogs, such as insulin гларгин, can significantly differ at different persons or at the same person.

Pharmacokinetics. Comparative study of concentration of insulin of a glargin and insulin isophane in blood serum at the healthy people and patients suffering from a diabetes mellitus after hypodermic administration of drugs revealed the slowed-down and much longer absorption, and also lack of peak of concentration at insulin of a glargin in comparison with insulin isofan.
At hypodermic administration of the drug Lantus® Solostar® single within a day equilibrium concentration of insulin of a glargin in blood is reached in 2-4 days of daily introduction.
At intravenous administration elimination half-lives of insulin of a glargin and human insulin were comparable.
At the person in a hypodermic fatty tissue insulin гларгин is partially split from the carboxyl end (S-end) of the R-chain (beta chain) with formation of 21A-01u-insulin and 21 A-Gly-des-30B-Thr-insulin. At plasma there are as not changed insulin гларгин, and products of its splitting.

Indications to use:

The diabetes mellitus demanding treatment by insulin at adults, teenagers and children is more senior than 6 years.

Route of administration and doses:

Subcutaneously to adults and children 6 years are more senior.
Lantus® Solostar® should apply only subcutaneously 1 time a day always at the same time. Lantus® Solostar® has to be entered into a hypodermic fatty tissue of a stomach, shoulders or hips. Places of injections have to alternate at each new injection within the recommended areas for hypodermic administration of drug.
The dose of the drug Lantus® Solostar® and time of day for its introduction is selected individually. At patients with a diabetes mellitus 2 Solostar® Lantus® types can be applied both in the form of monotherapy, and in a combination with other hypoglycemic medicines.
Transition from treatment by other hypoglycemic drugs on Lantus® Solostar®
When replacing the scheme of treatment with insulin of average duration of action or long action by the scheme of treatment with the drug Lantus® Solostar® correction of a daily dose of basal insulin can be required, and also arise need for change of the accompanying antidiabetic therapy (doses and the scheme of administration of in addition applied insulin of short action or their analogs or doses of peroral hypoglycemic drugs).
At transfer of patients from administration of insulin isophane double within a day on single administration of the drug Lantus® Solostar® for the purpose of decrease in risk of development of a hypoglycemia in night and early morning time it is necessary to reduce a daily dose of basal insulin by 20-30% in the first weeks of treatment. During this period a dose decline, at least, partially, it is necessary to compensate by increase in doses of insulin of short action, with the subsequent individual correction of the mode of dosing.
Lantus® Solostar® should not be mixed with other drugs of insulin or to part. It is necessary to be convinced that syringes did not contain the remains of other medicines. During the mixing or cultivation the profile of effect of insulin of a glargin in time can change. Mixing with other insulin can cause loss of a deposit.
As well as at use of other analogs of human insulin, at the patients receiving high doses of insulin owing to existence of antibodies to human insulin upon transition to Lantus® Solostar® increase in response to administration of insulin can be observed. In the course of transition to Lantus® Solostar® and to the first weeks after it careful monitoring content of glucose in blood and if necessary correction of the mode of dosing of insulin is required.
In case of improvement of metabolic regulation and the increase in sensitivity of fabrics caused by it to insulin there can be a need of further correction of the mode of dosing. Dose adjustment can be also required, for example, at change of body weight of the patient, his way of life, time of day for administration of drug or at emergence of other circumstances promoting increase in predisposition to development hypo - or a hyperglycemia.
The drug should not be administered intravenously. Intravenous administration of the usual dose intended for introduction subcutaneously can cause development of a heavy hypoglycemia.
Duration of effect of the drug Lantus® Solostar® depends on localization of the place of its hypodermic introduction.

Features of use:

Lantus® Solostar® is not choice drug for treatment of diabetic ketoacidosis. In such cases intravenous administration of insulin of short action is recommended.
Due to the limited experience of use of the drug Lantus® Solostar® there was no opportunity to estimate its efficiency and safety at treatment of patients with an abnormal liver function or patients with a medium-weight or heavy renal failure.
At patients with a renal failure the need for insulin can decrease in connection with delay of its elimination. At elderly patients the progressing deterioration in function of kidneys can lead to permanent decrease in need for insulin.
At patients with a heavy liver failure the need for insulin can be lowered in connection with decline in the ability to a gluconeogenesis and delay of biotransformation of insulin.
In case of inefficient control of the level of content of glucose in blood, and also in the presence of a tendency to development hypo - or a hyperglycemia before starting correction of the mode of dosing, it is necessary to check the accuracy of implementation of the ordered scheme of treatment, observance of instructions concerning injection sites of drug and correctness of the technology of carrying out subcutaneous injections taking into account all the factors influencing it.
Hypoglycemia
Time of development of a hypoglycemia depends on a profile of effect of the used insulin and can change, thus, when changing the scheme of treatment. Owing to increase in time of receipt in an organism of insulin of long action when using the drug Lantus® Solostar®, it is necessary to expect smaller probability of development of a night hypoglycemia whereas early morning hours this probability of development of a hypoglycemia is higher. At emergence of a hypoglycemia at the patients receiving Lantus® Solostar® it is necessary to consider a possibility of delay of an exit from a condition of a hypoglycemia in connection with the prolonged effect of insulin of a glargin.
To patients at whom episodes of a hypoglycemia can have special clinical value such as patients with the expressed stenosis of coronary arteries or vessels of a brain (risk of development of cardial and cerebral complications of a hypoglycemia), and also to patients with a proliferative retinopathy, especially if they do not receive treatment by photocoagulation (risk of passing loss of sight after a hypoglycemia) it is necessary to observe extra care and to intensify monitoring of level of glucose in blood.
Patients have to be warned about states at which symptoms harbingers of a hypoglycemia can decrease. At patients of separate risk groups symptoms of a hypoglycemia can change, become less expressed or be absent. Treat them:
- patients at whom regulation of content of glucose in blood considerably improved;
- patients at whom the hypoglycemia develops gradually;
- patients of advanced age;
- the patients transferred from insulin of animal origin on human insulin;
- patients with neuropathy;
- patients with the long anamnesis of a diabetes mellitus;
- the patients having mental disorders;
- the patients receiving the accompanying treatment by other medicines (see. "Interaction with other medicines").
Such situations can lead to development of a heavy hypoglycemia (with a possible loss of consciousness) before the patient realizes that it develops a hypoglycemia.
If normal or reduced indicators of glikozilirovanny hemoglobin are noted, it is necessary to consider a possibility of development of the repeating not recognizable hypoglycemia episodes (especially at night).
Observance by patients of the scheme of dosing and diet, the correct administration of insulin and knowledge of symptoms harbingers of a hypoglycemia promote essential decrease in risk of development of a hypoglycemia. The factors increasing tendency to a hypoglycemia in the presence of which especially careful observation is required and insulin dose adjustment can be necessary:
- change of an injection site of insulin;
- increase in sensitivity to insulin (for example,  at elimination of stressful factors);
- the unusual, increased or long physical activity;
- the intercurrent diseases which are followed by vomiting, diarrhea;
- disturbance of a diet and diet;
- the missed meal;
- alcohol consumption;
- some  noncompensated  endocrine  disturbances  (for example, hypothyroidism, insufficiency of an adenohypophysis or bark of adrenal glands);
- the accompanying treatment by some other medicines. Intercurrent diseases
At intercurrent diseases more intensive control of level of glucose in blood is required. In many cases carrying out the analysis on existence of ketonic bodies in urine is shown, correction of the mode of dosing of insulin also often is required. The need for insulin quite often increases. Patients with a diabetes mellitus of 1 type have to continue regular consumption, at least, of a small amount of carbohydrates even if they are capable to consume food only in small volumes or cannot eat at all or if they have a vomiting, etc., and they never have to stop administration of insulin at all.
At storage of the drug Lantus® Solostar®. in the refrigerator to watch that containers directly did not adjoin to a freezing compartment or the frozen packagings.
Before the first use it is necessary to sustain the syringe handle Lantus® Solostar® at the room temperature 1-2 hours.
Used one-time the syringe handle Solostar® it is necessary to store at a temperature not above 25 °C, to protect from light influence.
Previously filled the syringe handle Solostar® not to cool.

Side effects:

The hypoglycemia, the most often found undesirable effect of an insulin therapy, can arise if the dose of insulin is too high in comparison with the need for it.
The undesirable effects provided below are given on systems of bodies in a soovetstviye with the following gradation of frequency of their emergence:
Very often:       (> 10%),
Often:                 (> 1% - <10%);
Infrequently:               (> 0,1% - <1%);
Seldom:                  (0,01% - 0,1%);
Very seldom:        (<0,01%)
From metabolism
Very often:   hypoglycemia
Symptoms of development of a hypoglycemia usually arise suddenly. However often psychoneurological disturbances against the background of a neuroglycopenia (feeling of fatigue, unusual fatigue or weakness, decline in the ability to concentration of attention, drowsiness, visual frustration, a headache, nausea, confusion of consciousness or its loss, a convulsive syndrome) are usually preceded by symptoms of adrenergic counterregulation (activation of simpatokadrenalovy system in response to a hypoglycemia): feeling of hunger, irritability, nervous excitement or a tremor, concern, pallor of integuments, "cold" sweat, tachycardia, the expressed heartbeat (the quicker the hypoglycemia develops and than it is heavier, symptoms of adrenergic counterregulation are stronger expressed to those).
The attacks of a heavy hypoglycemia which are especially repeating can lead to defeat of a nervous system. Episodes of the long and expressed hypoglycemia can threaten life of patients as at increase of a hypoglycemia even death is possible.
From immune system
Seldom: allergic reactions
Allergic reactions of immediate type to insulin develop seldom. Similar reactions to insulin (including insulin гларгин) or excipients can be shown by development of generalized skin reactions, a Quincke's disease, bronchospasm, arterial hypotension or shock and can pose a threat of life of the patient, thus.
Use of insulin can cause antibody formation to it. Antibody formation, cross reacting with human insulin and insulin glarginy, is observed with an identical frequency at use of insulin isophane and insulin of a glargin. In rare instances, existence of such antibodies to insulin can cause the necessity of correction of the mode of dosing for the purpose of elimination of a tendency to development hypo - or a hyperglycemia.
From a nervous system
Very seldom: dysgeusia (food faddism)
From eyes
Seldom: vision disorders
Significant changes of regulation of content of glucose in blood can cause temporary vision disorders owing to change of turgor of fabrics and index of refraction of lens.
Seldom: retinopathy
Long-term normalization of content of glucose in blood reduces risk of progressing of a diabetic retinopathy. The insulin therapy which is followed by sharp fluctuations of content of glucose in blood can be followed by temporary deterioration in a course of a diabetic retinopathy. At the patients with a proliferative retinopathy who are especially not receiving treatments by photocoagulation, episodes of a heavy hypoglycemia can lead to development of passing loss of sight.
From skin and a hypodermic fatty tissue
Often: a lipodystrophy (at 1-2% of patients)
As well as at treatment by any other drugs of insulin, in the place of injections the lipodystrophy capable to slow down local absorption of insulin can develop
Infrequently: lipoatrophia
Constant change of places of injections within the areas of a body recommended for hypodermic administration of insulin can promote reduction of expressiveness of this reaction or prevent its development.
From musculoskeletal and connecting fabric
Very seldom: mialgiya
The general disturbances and reactions in an injection site
Often: reactions in an injection site (3-4%) (reddening, pain, an itch,
urticaria, hypostasis or inflammation)
The majority of insignificant reactions in an injection site of insulin are usually allowed in a span from several days to several weeks.
Seldom: sodium delay, hypostases (especially if intensified
insulin therapy leads to improvement of earlier insufficient metabolic control)
The safety profile for patients is younger than 18 years, generally, is similar to a safety profile for patients 18 years are more senior. At patients more young 18 years arise reactions in an injection site and skin reactions (rash, urticaria) rather more often
Data on safety at patients more young are absent than 6 years.

Interaction with other medicines:

Pharmakodinamichesky interaction
- Peroral hypoglycemic means, inhibitors
angiotensin-converting enzyme, Disopyramidum, fibrata, fluoxetine, monoamine oxidase inhibitors, пентоксифиллин, the propoxyhair dryer, salicylates and sulfanamide antimicrobic means - can strengthen hypoglycemic effect of insulin and increase predisposition to development of a hypoglycemia. The concomitant use with insulin glarginy can demand insulin dose adjustment.
- Glucocorticosteroids, даназол, diazoxide, diuretics, a glucagon, an isoniazid, estrogen and gestagena (for example, in hormonal contraceptives), derivative a fenotiazina, Somatotropinum, sympathomimetics (for example, Epinephrinum [adrenaline], salbutamol, тербуталин) and hormones of a thyroid gland, inhibitors of proteases, atypical neuroleptics (for example, olanzapine or clozapine) - can weaken hypoglycemic effect of insulin. The concomitant use with insulin glarginy can demand dose adjustment of insulin of a glargin
- Beta adrenoblockers, a clonidine, salts of lithium or alcohol - both strengthening, and weakening of hypoglycemic effect of insulin is possible.
- Pentamidine - at a combination to insulin can cause a hypoglycemia which sometimes is replaced by a hyperglycemia.
- Drugs of sympatholytic action, such as beta adrenoblockers, a clonidine, гуанетидин and Reserpinum - can decrease or be absent signs of adrenergic counterregulation (activation of a sympathetic nervous system) at development of a hypoglycemia.
Pharmaceutical interaction:
- When mixing the drug Lantus® Solostar® with other medicinal substances including with other insulin, and also cultivation of drug formation of a deposit or change of a profile of effect of drug in time is possible.

Contraindications:

• Hypersensitivity to insulin to a glargin or to any of auxiliary components of drug.
• Children's age up to 6 years (lack of clinical data on use). With care
Pregnant women (a possibility of change of need for insulin during pregnancy and after the delivery)
Pregnancy and feeding by a breast
In researches on animals direct or indirect data on embriotoksichesky or fetotoksichesky effect of insulin of a glargin were not obtained.
So far there are no relevant statistical data concerning use of drug during pregnancy. There are data on use of the drug Lantus® Solostar® for 100 pregnant women with a diabetes mellitus. The current and the result of pregnancy at these patients did not differ from those at the pregnant women with a diabetes mellitus receiving other drugs of insulin.
Purpose of the drug Lantus® Solostar® at pregnant women has to be carried out with care. Careful monitoring of level of glucose in blood is obligatory.
For patients with earlier being available or gestational diabetes mellitus it is important to support glycemic control during all pregnancy. The need for insulin can decrease in the first trimester of pregnancy and, in general, increase during the second and third trimesters. Directly after the delivery the need for insulin quickly decreases (the risk of development of a hypoglycemia increases). In these conditions essential value has careful control of concentration of glucose in blood.
At women during feeding by a breast correction of the mode of dosing of insulin and a diet can be required.
Route of administration and doses
Subcutaneously to adults and children 6 years are more senior.
Lantus® Solostar® should apply only subcutaneously 1 time a day always at the same time. Lantus® Solostar® has to be entered into a hypodermic fatty tissue of a stomach, shoulders or hips. Places of injections have to alternate at each new injection within the recommended areas for hypodermic administration of drug.
The dose of the drug Lantus® Solostar® and time of day for its introduction is selected individually. At patients with a diabetes mellitus 2 Solostar® Lantus® types can be applied both in the form of monotherapy, and in a combination with other hypoglycemic medicines.
Transition from treatment by other hypoglycemic drugs on Lantus® Solostar®
When replacing the scheme of treatment with insulin of average duration of action or long action by the scheme of treatment with the drug Lantus® Solostar® correction of a daily dose of basal insulin can be required, and also arise need for change of the accompanying antidiabetic therapy (doses and the scheme of administration of in addition applied insulin of short action or their analogs or doses of peroral hypoglycemic drugs).
At transfer of patients from administration of insulin isophane double within a day on single administration of the drug Lantus® Solostar® for the purpose of decrease in risk of development of a hypoglycemia in night and early morning time it is necessary to reduce a daily dose of basal insulin by 20-30% in the first weeks of treatment. During this period a dose decline, at least, partially, it is necessary to compensate by increase in doses of insulin of short action, with the subsequent individual correction of the mode of dosing.
Lantus® Solostar® should not be mixed with other drugs of insulin or to part. It is necessary to be convinced that syringes did not contain the remains of other medicines. During the mixing or cultivation the profile of effect of insulin of a glargin in time can change. Mixing with other insulin can cause loss of a deposit.
As well as at use of other analogs of human insulin, at the patients receiving high doses of insulin owing to existence of antibodies to human insulin upon transition to Lantus® Solostar® increase in response to administration of insulin can be observed. In the course of transition to Lantus® Solostar® and to the first weeks after it careful monitoring content of glucose in blood and if necessary correction of the mode of dosing of insulin is required.
In case of improvement of metabolic regulation and the increase in sensitivity of fabrics caused by it to insulin there can be a need of further correction of the mode of dosing. Dose adjustment can be also required, for example, at change of body weight of the patient, his way of life, time of day for administration of drug or at emergence of other circumstances promoting increase in predisposition to development hypo - or a hyperglycemia.
The drug should not be administered intravenously. Intravenous administration of the usual dose intended for introduction subcutaneously can cause development of a heavy hypoglycemia.
Duration of effect of the drug Lantus® Solostar® depends on localization of the place of its hypodermic introduction.

Overdose:

The overdose of insulin can bring to heavy and sometimes a long hypoglycemia, life-threatening the patient.
Treatment
Episodes of a moderate hypoglycemia are usually stopped by intake of quickly assimilable carbohydrates. There can be a need of change of the scheme of a drug dosing, diet or physical activity.
The episodes of heavier hypoglycemia which are shown a coma spasms or neurologic frustration demand intramuscular or hypodermic introduction of a glucagon, and also intravenous administration of strong solution of a dextrose (glucose). Long reception of carbohydrates and observation of the specialist as after visible clinical improvement the hypoglycemia recurrence is possible can be required.

Storage conditions:

At a temperature from 2 °C to 8 °C in the place protected from light. Not to freeze! To store in the place, unavailable to children! Period of validity 3 years. After a period of validity drug cannot be used.

Issue conditions:

According to the recipe

Packaging:

Solution for hypodermic introduction of 100 PIECES/ml.
On 3 ml of drug in a cartridge from transparent, colourless glass (type I). The cartridge is corked on the one hand by a brombutilovy stopper and pressed out by an aluminum cap, on the other hand - a brombutilovy plunger.
The cartridge is built in in one-time the syringe handle Solostar®. On the 5th syringe handles Solostar® together with the application instruction in the cardboard pack supplied with the cardboard fixer.