LANTUS

Active material: Insulin glargine
When ATH: A10AE04
CCF: A long-acting human insulin
ICD-10 codes (testimony): E10, E11
When CSF: 15.01.01.04
Manufacturer: SANOFI-AVENIS Germany GmbH (Germany)

Pharmaceutical form, composition and packaging

The solution for the p / to the introduction clear, colorless or near colorless.

Excipients: cresol (m-cresol), zinc chloride, glycerol (85%), Sodium hydroxide, hydrochloric acid, water d / and.

3 ml – flint glass cartridges (5) – packings Valium planimetric (1) – packs cardboard.
3 ml – flint glass cartridges (1) – pen OptiSet (5) – packs cardboard.
3 ml – flint glass cartridges (1) – Cartridge system OptiKlik (5) – packs cardboard.

Pharmacological action

Insulin glargine is a human insulin analogue. Obtained by recombinant DNA the bacterium Escherichia coli (strains K12). It features a low solubility in a neutral environment. As part of Lantus^® it is completely soluble, provided that the acidic medium solution for injection (pH = 4). After the introduction of subcutaneous fat solution because of its acidity reacts with the formation of neutralizing mikropretsipitatov, of which are constantly released small amounts of insulin glargine, providing a smooth (without peaks) profile curve “concentration-time”, as well as a longer duration of action of the drug.

Parameters binding to insulin receptors of insulin glargine and human insulin very close. Insulin glargine has a biological effect similar to endogenous insulin.

The most important action of insulin is the regulation of glucose metabolism. Insulin and its analogs lower blood glucose, stimulating glucose uptake by peripheral tissues (especially skeletal muscle and adipose tissue), and inhibiting glucose production in the liver (gluconeogenesis). Insulin inhibits lipolysis in adipocytes and proteolysis, while increasing protein synthesis.

The increased duration of action of insulin glargine is directly due to the low rate of its absorption, allowing you to use the drug 1 time / day. Valid average – through 1 h after s / to the introduction. Average duration – 24 no, maximum – 29 no. The nature of the action of insulin and its analogues (eg, insulin glargine) time may vary considerably in different patients as a, and one and the same patient.

The duration of action of Lantus^® due to its introduction into the subcutaneous fat.

Pharmacokinetics

A comparative study of concentrations of insulin glargine and insulin-Isophane after s / to the introduction in the serum of healthy people and patients with diabetes showed delayed significantly longer absorption, and no peak concentrations in insulin glargine compared with insulin isophane.

When s / c administration of the drug 1 time / day steady average concentration of insulin glargine in blood achieved through 2-4 day after the first dose.

The on / in a T_1/2 insulin glargine and human insulin are comparable.

The man in the subcutaneous fat insulin glargine was partially digested by the carboxyl terminus (From the end) The chain (beta chain) to form 21^A-Insulin and Gly- 21^A-Gly-des-30^B-Thr-insulin. The plasma contains both unmodified insulin glargine, and its cleavage products.

Testimony

- Diabetes, requiring insulin treatment, adult, adolescents and children over 6 years.

Dosage regimen

Dose and time of day for his conduct set individually. Lantus^® introduced n / a 1 time / day, and always at the same time. Lantus^® should be administered in subcutaneous fat belly, shoulder or hip. Injection site should be alternated at each new introduction of the drug within the recommended areas for s / c administration.

The drug can be applied as a monotherapy, or in combination with other hypoglycemic drugs.

When transferring a patient with insulin or a long average duration to Lantus^® It may require correction daily dose of basal insulin or antidiabetic therapy concomitant change (dosage and mode of administration of short-acting insulin or their analogues, as well as the dose of oral hypoglycemic drugs).

When transferring a patient with double-insulin isophane on a single administration of Lantus ®^® should reduce the daily dose of basal insulin 20-30% in the first weeks of treatment to reduce the risk of hypoglycemia during the night and early morning hours. During this period, a dose reduction Lantus ®^® should be compensated by increasing doses of short-acting insulin, followed by individual correction mode.

As with other analogs of human insulin, patients, receiving high doses of the drugs because of the presence of antibodies to human insulin, when switching to Lantus^® may experience increased response to insulin. In the process of transition to Lantus^® and during the first week after it requires careful control of blood glucose and if necessary – correction dosing regimen of insulin.

In the case of improving the regulation of metabolism and the resulting increase in insulin sensitivity may be a need for further correction mode. Dose adjustment may also be required, eg, Change in body weight, his lifestyle, the time of day for administration of the drug or when other circumstances, contributing to increased susceptibility to the development of hypo-- or hyperglycemia.

The drug should not be administered in /. In / in a normal dose, designed to s / c administration, It can cause the development of severe hypoglycemia.

Before the introduction, make sure, in syringes that do not contain residues of other drugs.

Terms of Use and the treatment of drug

Pre-filled pen OptiSet

Before use, inspect the cartridge inside the pen. It should be used only in case of, if the solution is clear, bestsveten, It does not contain visible particles and the consistency of water. Empty pen OptiSet not designed for reuse and must be destroyed.

To prevent infection prefilled syringe pen designed for use with one patient and not be transferred to another person.

Handling the syringe handle OptiSet

With each successive application should always use a new needle. Only use needles, suitable for pen OptiSet.

Before each injection, you should always carry out a test on safety.

If you use a new syringe pen OptiSet, check ready for use shall be carried out using 8 units, pre-typed manufacturer.

The dose selector can be rotated in only one direction.

Never turn the dose selector (dose change) After clicking on the start button injection.

If an injection of the patient makes the other person, it will need to take special care to avoid accidental needle injury and infection contagious.

Never use damaged the pen OptiSet, as well as a suspected malfunction.

It is necessary to have a spare OptiSet the pen in case of loss or damage to used.

Checking the insulin

After removing the cap from the pen, check the markings on the insulin reservoir, to make sure, that it contains the correct insulin. You should also check the appearance of insulin: insulin solution should be clear, colorless, not contain visible particulates, and have a consistency, Like water. Do not use the pen OptiSet, if the solution is cloudy insulin, colored or contains foreign particles.

Attaching the needle

After removing the cap should be carefully and tightly connect the needle to the syringe handle.

Check pen ready to use

Prior to each injection, you must inspect the pen ready to use.

For a new and unused pen pointer dose should stand on the figure 8, as it was billed in advance by the manufacturer.

If the syringe pen used, dispenser should be rotated until, dose until the pointer stops at the figure 2. The dispenser will only rotate in one direction.

Pull the release button is fully, to dial a dose. Never turn the dose selector after the start button is pulled out.

The outer and inner needle caps should be removed. Save the outer cap, to remove the used needle.

Hold the pen with the needle, upward, It should be gently tapped his finger on the insulin reservoir to, so that air bubbles rose up towards the needle.

This is followed all the way to press the start button.

If a drop of insulin released from the tip of the needle, syringe pen and needle work correctly.

If a drop of insulin does not appear at the needle tip, Repeat test pen ready to use until, Insulin is not visible at the tip of the needle.

Choosing the insulin dose

It can be set dose from 2 units to 40 unit increments 2 units. If you need a dose, exceeding 40 units, it should be administered in two or more injections. Check, that you have enough insulin for the desired dose.

Residual insulin scale on the transparent container shows how much insulin, about, insulin left in the syringe handle OptiSet. This scale can not be used for taking insulin dose.

If the black plunger is at the beginning of the color strip, so, there is, about, 40 insulin units.

If the black plunger is at the end of a color strip, so, there is, about, 20 insulin units.

The dosage selector should be rotated, until the dose arrow points to the required dose.

Fence insulin dose

Launcher button injections need to get to the limit, to fill an insulin pen.

You should check, It is fully typed the correct dose. Start button moves according to the amount of insulin, remaining in the vessel for insulin.

Start button lets you check, Cocoa dose typed. During the inspection start button must be held under tension. The last thick line visible on the launch button shows the amount of insulin taken away. When the start button withheld, visible only the upper part of the broad lines.

Insulin

Specially trained staff should explain to the patient the injection technique.

The needle is inserted n / a. Injection start button must be pressed to the limit. There was a click stop, when the start button is pressed to the injection failure. Then, the injection start button must be kept pressed for 10 seconds before, than pull the needle out of the skin. This will ensure that the introduction of the entire dose of insulin.

Removing the needle

After each injection, the needle should be removed from the pen and discard the. This will prevent infection, and leakage of insulin, air intake and possible clogging of the needle. Needles should not be reused.

After that you should put on the back cap pen.

Cartridges

Cartridges should be used with a syringe-pen OptiPen pro1, and in accordance with recommendations, data device manufacturer.

Instructions for using the pen OptiPen pro1 on installing the cartridge, connecting the needle and the injection of insulin should be accurately performed. Inspect the cartridge before use. It should be used only if, if the solution is clear, colorless and does not contain visible particulates. Before installing the cartridge in the pen cartridge must 1-2 hours, kept at room temperature. Before injection, the cartridge must be removed from air bubbles. It is necessary to strictly follow the instructions. Empty cartridges are not reused. If the syringe pen OptiPen pro1 damaged, you can not use it.

If the syringe handle is faulty, if necessary can be administered to a patient insulin, typing solution from the cartridge into a plastic syringe (suitable for insulin concentration 100 IU / mL).

To prevent infection with the syringe-pen refillable should benefit only one person.

Cartridge system OptiKlik

OptiKlik cartridge system is a glass cartridge, comprising 3 ml of insulin glargine, which is placed in a transparent plastic container with attached piston mechanism.

OptiKlik cartridge system should be used in conjunction with a syringe-handle OptiKlik in accordance with the instructions for use, attached to it.

It is precisely to carry out all the recommendations, contained in the instructions on the installation of the cartridge in the pen OptiKlik, connecting the needle and the injection.

If the syringe pen OptiKlik damaged, should be replaced with a new one.

Before installation of the cartridge system in the pen, it should OptiKlik 1-2 hours, kept at room temperature. Before installing the cartridge system should be inspected. It should be used only in the event, if the solution is clear, colorless and does not contain visible particulates. Prior to injection of the cartridge system, remove air bubbles (as well as by using the pen). Blank cartridge system are not reused.

If the syringe handle is faulty, then in case of need can be administered to a patient insulin, typing solution from the cartridge into a plastic syringe (suitable for insulin concentration 100 IU / mL).

To prevent infection with the syringe-pen refillable should benefit only one person.

Side effect

Determination of the frequency of adverse reactions: Often (≥ 10%), often (≥ 1%, <10); sometimes (≥ 0.1%, < 1%); rarely (≥ 0.01%, < 0.1%), rarely (< 0.01%).

Side effects, related to the effect on carbohydrate metabolism: hypoglycaemia develops most often, if the insulin dose exceeds the demand for it.

Attacks of severe hypoglycemia, especially repetitive, can lead to shock the nervous system. Episodes long and expressed hypoglycemia may endanger patients' lives.

Neuropsychiatric disorders against the background of hypoglycemia (“twilight” or loss of consciousness, convulsions) usually preceded by symptoms of adrenergic counterregulation (activation of the sympathetic-adrenal system in response to hypoglycemia): hunger, irritability, cold sweat, tachycardia (the faster and greater developing hypoglycaemia, the more pronounced the symptoms of adrenergic counterregulation).

On the part of the organ of vision: rarely – visual impairment, retinopathy.

Significant changes in the regulation of blood glucose can cause temporary visual impairment due to changes in tissue turgor and refractive index of the lens of the eye.

The long-term normalization of blood glucose reduces the risk of progression of diabetic retinopathy. Against the background of insulin, accompanied by sharp fluctuations in blood glucose, possible temporary worsening of diabetic retinopathy. Patients with proliferative retinopathy, especially untreated photocoagulation, episodes of severe hypoglycemia can lead to the development of transient loss of vision.

Skin and subcutaneous fat: often – as well as in the treatment of any other insulin preparations, vozmozhnы lipodystrophy (1-2%) and delay local insulin absorption; infrequently – lipoatrophy. Constant change of the injection site within the body regions, recommended for s / c insulin, It can reduce the severity of this reaction or prevent its development.

From the nervous system: rarely – disgevziya.

On the part of the musculoskeletal system: rarely – myalgia.

Metabolism: rarely – sodium retention, swelling (especially, If Intensified insulin therapy leads to an improvement in the previously inadequate regulation of metabolic processes).

Allergic reactions: rarely – immediate type allergic reactions to insulin (including insulin glargine) or formulation auxiliary components – generalized skin reactions, angioedema, bronchospasm, hypotension, shock. These reactions can be life-threatening patient.

The use of insulin can induce the formation of antibodies thereto. Antibody formation, cross-react with human insulin, observed with the same frequency. In rare cases, the presence of antibodies to insulin may necessitate dose adjustment in order to eliminate the tendency to the development of hypo- or hyperglycemia.

Local reactions: often (3-4%) – redness, pain, itch, hives, swelling or inflammation at the injection site. In most cases, minor reactions resolved within a period of from several days to several weeks.

The safety profile for patients younger than 18 years basically similar safety profile in patients older 18 years. In patients younger than 18 years of relatively more likely to have injection site reactions and skin reactions (rash, hives). The safety data in children under 6 missing years.

Contraindications

- Children up to age 6 years (clinical data for use at the present time no);

- Hypersensitivity to the drug.

FROM caution to use Lantus^® Pregnancy.

Pregnancy and lactation

Caution should be used Lantus^® Pregnancy.

For patients with pre-existing or gestational diabetes is important during pregnancy to maintain adequate regulation of metabolism. In the I trimester of pregnancy, insulin requirements may be reduced, in II and III trimesters – increase. Immediately after delivery insulin requirements decreased, and therefore increases the risk of hypoglycemia. Under these conditions is essential careful monitoring of blood glucose.

IN experimental studies animal has been received direct or indirect data embryotoxic or foetotoxic effect of insulin glargine.

Controlled clinical studies safety of Lantus^® during pregnancy was conducted. There is evidence of the use of Lantus ®^® in 100 Pregnant women with diabetes. The course and outcome of pregnancy in these patients did not differ from those of pregnant women with diabetes, receiving other insulin preparations.

In women during the period of breast-feeding may require correction dosing regimen of insulin and diet.

Cautions

Lantus^® not the drug of choice for the treatment of diabetic ketoacidosis. In such cases, in / in a short-acting insulin.

Due to the limited experience of using Lantus ®^® it was not possible to assess its efficacy and safety in patients with impaired liver function or renal insufficiency patients moderate or severe.

In patients with renal impairment, insulin requirements may be reduced due to the weakening of its elimination. Elderly patients progressive deterioration of renal function may lead to a permanent reduction in insulin requirements.

In patients with severe liver failure, insulin requirements may be reduced due to the reduced capacity for gluconeogenesis and biotransformation insulin.

In the case of poor control of glucose levels in the blood, as well as a trend towards the development of hypo- or hyperglycemia, before embarking on the correct dosing regimen, check the accuracy of compliance with prescribed regimens, Places of administration and technology literate of s / c injection, taking into account all the factors affecting.

Gipoglikemiâ

Time of hypoglycemia depends on the action profile of insulin and may be used, thus, changed by changing the treatment regimen. Due to the increase of time of exposure of long-acting insulin Lantus ® when used^®, expect less likelihood of nocturnal hypoglycemia, whereas in the early hours of this probability is higher. In the event of hypoglycemia in patients, receiving Lantus^®, should consider the possibility of slowing down the output from the state of hypoglycaemia due to the prolonged action of insulin glargine.

Patients, who have hypoglycemia may be of particular clinical relevance, incl. in severe stenosis of the coronary arteries or blood vessels of the brain (the risk of cardiac and cerebral complications of hypoglycaemia), as well as patients with proliferative retinopathy, especially if they do not receive treatment photocoagulation (risk of transient loss of vision due to hypoglycemia), should take special precautions and carefully monitored blood glucose.

Patients should be warned about the states, in which the symptoms of hypoglycemia-precursors may be reduced, be less pronounced or be absent in certain risk groups, which include:

- Patients, which significantly improved the regulation of blood glucose;

- Patients, who hypoglycaemia develops gradually;

- Elderly patients;

- Patients with neuropathy;

- Patients with a long history of diabetes;

- Patients, mental disorders;

- Patients, Translated animal insulin to human insulin;

- Patients, receiving concomitant treatment with other drugs.

Such situations can lead to the development of severe hypoglycemia (with possible loss of consciousness) before that, the patient understands, he develops hypoglycemia.

When, If there is normal or reduced performance of glycated hemoglobin, you must consider the possibility of repeating unrecognized hypoglycemia (especially at night).

Respect for patient dosing, diet and nutrition, the correct use of insulin and control symptoms of hypoglycemia contributed significantly reduce the risk of hypoglycaemia. In the presence of factors, increase susceptibility to hypoglycaemia, It must be particularly careful observation, tk. may require dose adjustment of insulin. These factors include:

- Change of insulin;

- Increase insulin sensitivity (eg, while eliminating stress factors);

- Unaccustomed, increased or prolonged physical activity;

- Intercurrent illness, accompanied by vomiting, diarrhea;

- Violation of diet and nutrition;

- Skipping meals;

- Alcohol consumption;

- Certain uncompensated endocrine disorders (eg, gipotireoz, lack of anterior pituitary or the adrenal cortex);

- Other concomitant therapy with certain drugs.

Intercurrent disease

When intercurrent diseases require more intensive control of blood glucose. In many cases, the analysis indicated the presence of ketone bodies in urine, often requires correction dosing regimen of insulin. Insulin requirements often increases. Diabetics type 1 We should continue to regular consumption, at least, a small amount of carbohydrates, even when eating only in small amounts, or without the possibility to eat, and at vomiting. These patients should never completely stop insulin.

Overdose

Symptoms: sometimes heavy and prolonged hypoglycemia, threatening the life of the patient.

Treatment: episodes of moderate hypoglycemia usually cropped by ingestion of fast utilizable carbohydrates. It may be necessary to change the dosing of the drug, diet and physical activity.

Episodes of more severe hypoglycemia, accompanied by coma, convulsions or neurological disorders, demand / m or s / c injection of glucagon, and / in the introduction 40% dextrose. You may need long-term use of carbohydrates and surveillance specialist, tk. possible recurrence of hypoglycaemia after apparent clinical improvement.

Drug Interactions

Oral hypoglycemic agents, ACE inhibitors, disopyramide, fibrates, fluoxetine, MAO inhibitors, pentoxifylline, dextropropoxyphene, salitsilatы and sulyfanilamidnыe protivomikrobnыe means Mughals usility gipoglikemicheskoe insulin action and povыsity predraspolozhennosty k razvitiyu gipoglikemii. In these combinations may require dose adjustment of insulin glargine.

GCS, danazol, diazoksid, Diuretic, glucagon, Isoniazid, Estrogens, progestins, phenothiazines, somatotropin, sympathomimetic (eg, epinephrine, salbutamol, terbutaline), thyroid hormones, protease inhibitors, Some antipsychotics (eg, olanzapine or clozapine) may reduce the hypoglycemic effect of insulin. In these combinations may require dose adjustment of insulin glargine.

With simultaneous use of Lantus^® with beta-blockers, clonidine, lithium salts, ethanol as a possible enhancement, and the weakening of the hypoglycemic action of insulin. Pentamidine in combination with insulin can cause hypoglycaemia, which is sometimes replaced by hyperglycemia.

In an application with drugs, having sympatholytic action, such as beta- adrenoblokatorы, klonidin, guanfacine and reserpine may decrease or absence of signs of adrenergic counterregulation (Activation of the sympathetic nervous system) the development of hypoglycemia.

Pharmaceutical interaction

Lantus^® should not be mixed with other insulin preparations, with any other drugs or breed. When mixing or breeding may change the profile of its actions in time, Besides, A mixture with other insulin can cause precipitation.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

The drug should be stored out of reach of children, dark place at a temperature of 2 ° to 8 ° C; Do not freeze. Shelf life – 3 year.

Once you start using cartridges, pre-filled pen OptiSet and cartridge system OptiKlik stored out of reach of children, protected from light, at a temperature no higher than 25 ° C. To protect from the effects of light pre-filled pen OptiSet, cartridges and cartridge system OptiKlik should be stored in their own cartons.

The pre-filled syringe pen OptiSet not cool.

After the first use of the shelf life of the drug cartridges, pre-filled pen OptiSet and cartridge system OptiKlik – 4 of the week. It is recommended to mark the date on the label of the first intake of the drug.