Lantus 300 IU SOLOSTAR PEN 3 ml

Qualitative and quantitative composition

Each ml contains 100 units insulin glargine (equivalent to 3,64 mg).

Each pen contains 3 ml solution for injection, equivalent to 300 units

Insulin glargine is produced by recombinant DNA technology in Escherichia coli.

CLINICAL DATA

 Witness

For the treatment of diabetes mellitus in adults, adolescents and children of 6 years or above, who require treatment with insulin.

 Dosage and method of administration

Dosage

Lantus contains insulin glargine, an insulin analogue with prolonged action.

Lantus should be administered once daily at any time, but every day at the same time.

Dosing regimen of Lantus (dosage and time of administration) should be performed

individually. In patients with type 2 diabetes mellitus, Lantus can also be used in

combination with oral antidiabetic agents.

The potency of this medicinal product is expressed in units. These units are

exclusive to Lantus and are not the same as IU or the units used to express the

potency of other insulin analogues. See section 5.1 (Pharmacodynamics).

Polpulatsiya elderly (> 65 years)

In the elderly, progressive deterioration of renal function may

lead to a steady decrease in insulin requirements.

Renal impairment

In patients with renal impairment, insulin requirements may be diminished due

reduced insulin metabolism.

Hepatic Impairment

In patients with hepatic impairment, insulin requirements may be diminished due

reduced capacity for gluconeogenesis and reduced insulin metabolism. 3

Paediatric population

The safety and efficacy of Lantus has been demonstrated in adolescents and children of 6 years.

In children, the efficacy and safety of Lantus have only been demonstrated when given in the evening.

Due to limited experience on the efficacy and safety of Lantus in children under 6

years, Lantus can be used in this age group under careful medical

observation.

Transition from other insulins to Lantus

When changing from a treatment regimen with a median duration of insulin action

or long-acting this to a regimen with Lantus, you may need a change in

basal insulin dose adjustment and the concomitant antidiabetic treatment

(Dose and timing of additional regular insulins or analogues

regular insulin or dose of oral antidiabetic drugs

products).

To reduce the risk of nocturnal and early morning hypoglycaemia, patients who changed

primary treatment with insulin twice daily NPH (Insulin average

duration of action) of Lantus once daily should during the first week

treatment to reduce their daily dose of basal insulin by 20-30%. During the first

weeks the reduction should be at least partly offset by increasing the dose of

insulin at mealtimes, after this period the regimen should be adjusted

individually.

As with other insulin analogues, patients with high insulin doses due

antibody against human insulin may have improved insulin response

the use of Lantus.

During the transition and the first weeks, it is recommended strict metabolic

traking.

With improved metabolic control and resulting increase

insulin sensitivity may require further adjustment

dose regimens. Dose adjustment may also be required, for example, if the weight of

patient or life-style changes, change of timing of insulin

or if other circumstances arise that increase susceptibility to hypo-or

hyperglycemia.

Route of administratio

Lantus is administered subcutaneously.

Lantus should not be administered intravenously. The prolonged effect of Lantus depends

injected into the subcutaneous tissue. Intravenous administration of the usual subcutaneous

dose could result in severe hypoglycemia.

No clinically significant differences in serum insulin or glucose levels

after the administration of Lantus abdominal, deltoid or thigh. Sites

injection sites should be rotated within the same region of injection for each

injetion.

Lantus must not be mixed with any other insulin should not be diluted.

Mixing or diluting can change its time / action profile and

mixing can cause precipitation.

 Contraindications

Hypersensitivity to the active substance or to any of the excipients.

 Special precautions for use

Lantus is not the insulin of choice for the treatment of diabetic ketoacidosis. Instead, in such

cases recommended intravenous regular insulin.

In case of insufficient glucose control or a tendency to hyper-or hypoglycaemic

episodes,'s adherence to the prescribed treatment regimen patient injection

sites and proper injection technique and all relevant factors before taking account

dose adjustment.

Transferring a patient to another type or brand of insulin should be done

under strict medical supervision. Changes in strength, brand (manufacturer)

type (regular, NPH, lente, long-acting, etc.), origin (animal, human, human

insulin analogue) and / or method of manufacture may result in the need for change

dose.

Insulin administration may cause insulin antibodies. In rare

cases, the presence of such insulin antibodies may necessitate adjustment in dosage

insulin to correct a tendency to hyper-or hypoglycemia

Hypoglycemia

The time of occurrence of hypoglycaemia depends on the action profile of the used

insulin, so it can be changed with a change in the treatment regimen. Due to -

delayed basal insulin supply with Lantus, can expect less nocturnal but

more early morning hypoglycaemia.

Tryavba to pay special attention and recommended intensive monitoring

blood glucose in patients in whom hypoglycaemic episodes might be of particular

clinical relevance, such as patients with significant coronary artery stenosis

or vessels of the brain (risk of cardiac or cerebral complications of hypoglycaemia) as well

and patients with proliferative retinopathy, particularly if not treated with photocoagulation (risk of

transient amaurosis following hypoglycaemia).

Patients should be aware of circumstances where warning symptoms

hypoglycaemia are diminished. The warning symptoms of hypoglycaemia may

be changed, be less pronounced or be absent in certain risk groups. They

patients include:

 In whom glycemic control is markedly improved,

 In whom hypoglycaemia develops gradually,

Who are elderly,

 After transfer from animal insulin to human insulin,

 Where there is an autonomic neuropathy

With long-standing diabetes

Suffering from mental illness

Receiving concurrent treatment with certain other medicinal products (see section 4.5).

Such situations may result in severe hypoglycaemia (and possibly loss of consciousness)

before the patient's awareness of hypoglycaemia.

The prolonged effect of subcutaneous insulin glargine may time

recovery from hypoglycemia.

If normal or decreased values for glycated hemoglobin should be

Given the possibility of recurrent, unrecognized (especially nocturnal) episodes of

hypoglycaemia.

Adherence of the patient to the dosage and dietary regimen, correct

insulin and awareness of hypoglycaemia symptoms are essential to reduce

the risk of hypoglycemia. Factors increasing the susceptibility to hypoglycaemia require

particularly close monitoring and may require dose adjustment. They include:

 Change in the injection area

 Improved insulin sensitivity (eg by removal of stress factors),

 Unaccustomed, increased or prolonged physical activity,

 Intercurrent illness (eg vomiting, diarrhea)

 Inadequate food intake,

 Skipping meals,

Alcohol consumption,

 Certain uncompensated endocrine disorders (eg in hypothyroidism and in anterior

pituitary or adrenocortical insufficiency)

 Concomitant treatment with certain other medicinal products.

Intercurrent illness

Intercurrent illness requires intensive metabolic monitoring. In many cases

shows urine tests for ketones and often necessary to adjust the dose

insulin. Insulin requirement is often increased. Patients with type 1 diabetes must continue

to regularly consume at least a small amount of carbs, even if they are able to

take little or no food, or are vomiting etc., should never be

omit insulin entirely.

 Interactions

A number of substances affect glucose metabolism and may require adjustment

dose of human insulin.

Substances that may enhance the blood glucose lowering effect and increase

hypoglycaemia include oral antidiabetic medicines

Angiotensin-converting enzyme (ACE), disopyramide, fibrates, fluoxetine,

monoamine oxidase (MAO) inhibitors, pentoxifylline, propoxyphene, salicylates and

sulphonamides.

Substances that may reduce the blood glucose lowering effect include

corticosteroids, danazol, diazoxide, diuretics, glucagon, isoniazid, oestrogens and

progestogens, phenothiazine derivatives, somatropin, sympathomimetic drugs

products (such as epinephrine [adrenaline], salbutamol, terbutaline), thyroid hormones

atypical antipsychotic agents (napr.klozapin and olanzapine) and protease

inhibitors.

Beta-blockers, clonidine, lithium salts or alcohol may either potentiate or weaken the

blood glucose lowering effect of insulin. Pentamidine may cause

hypoglycaemia, which may sometimes be followed by hyperglycaemia.

In addition, under the influence of sympatholytic medicinal products such as

for example. beta-blockers, clonidine, guanethidine and reserpine, the signs of adrenergic

counter-regulation may be reduced or absent.

Based on data that became available after the first authorization

for use, the Committee for Medicinal Products for Human Use (CHMP) considered that

benefit-risk balance of Lantus remains positive, but believes that his profile

Safety should be closely monitored for the following reasons:

 After the publication of four epidemiological studies on cancer risk (of

breast) in the use of insulin glargine in the journal Diabetologia, emerged

considerations on safety of insulin glargine in this regard. At this

now been launched three post-marketing pharmacoepidemiological studies MAH for

ponatatachno study of the possible increased risk of cancer associated with the use of insulin

glargine. These studies is planned to be completed over the next three years.

Based on this and in accordance with Article 14.3 of the EC Regulation (N0) 726/2004, CHMP is

believes that further five-year renewal based on the opinion

Pharmacovigilance.

 CHMP decided that the MAH should continue to submit yearly PSURs.

Therefore, based on the safety profile of Lantus, which requires the submission

annual PSUR, CHMP concluded that the MAH should submit an application for an additional

renewal period of five years.

 Use during pregnancy and lactation

Pregnancy

For insulin glargine no clinical data from controlled clinical trials are

in pregnant women. Limited amount of data on pregnant women (between 300 -

1000 outcome of pregnancy), exposure to marketed insulin glargine indicate no

side effects of insulin glargine on pregnancy and lack of teratogenicity and

fetal / neonatal toxicity of insulin glargine.

Daniel from studies in animals have shown reproductive toxicity.

If necessary, you should discuss the use of Lantus in pregnancy.

Patients with pre-existing or gestational diabetes, pregnancy diabetes

to maintain good metabolic control throughout pregnancy. During

first trimester, insulin requirements may be reduced and generally increase

During the second and third trimesters. Immediately after delivery, insulin requirements

dramatically decreased (increased risk of hypoglycaemia). Careful monitoring of blood glucose

esential

Breastfeeding

It is unknown whether insulin glargine is excreted in breast milk. No metabolic

effects of ingested insulin glargine on the breastfed newborn / child, since insulin glargine

as petid breaks down into amino acids in the human gastrointestinal tract. Breastfeeding

women may require adjustments in insulin dose and diet.

Fertility

Animal studies do not indicate direct harmful effects with respect to

fertility.

 Effects on ability to drive and use machines

The patient's ability to concentrate and react may be impaired as a result of

hypoglycaemia or hyperglycaemia, or as a result of visual impairment. This can

constitute a risk in situations where these abilities are of special importance (eg

driving a car or operating machinery).

Patients should be advised to take precautions to avoid hypoglycaemia while

driving. This is particularly important in those who have reduced or absent awareness of

hypoglycaemia or have frequent episodes of hypoglycaemia.

It should be considered whether it is advisable to drive or operate machinery when

these circumstances.

 Adverse reactions

Hypoglycaemia, in general the most frequent undesirable effect of insulin therapy, may

occur if the insulin dose is too high in relation to the insulin requirement. Frequencies:

Very common: Hypoglycaemia

Common: Reactions at the injection site, Lipohypertrophy

Uncommon: Lipoatrophy

Rare: Allergic reactions, visual impairment, retinopathy, edema

Very rare: myalgia, myalgia

Metabolism and nutrition

Severe hypoglycaemic attacks, especially if recurrent, may lead to

neurological damage. Prolonged or severe hypoglycaemic episodes may be

life-threatening.

In many patients, the signs and symptoms of neuroglycopenia are preceded by signs

of adrenergic counter. In general, the greater and more rapid the decline in

blood sugar, the more marked is the phenomenon of counter-regulation and its symptoms.

Immune System

Allergic immediate reactions to insulin are rare. Such reactions to insulin

(Including insulin glargine) or the excipients may, for example, be related to

generalized skin reactions, angioedema, bronchospasm, hypotension and shock, and may be

life-threatening.

Insulin administration may cause insulin antibodies. During

clinical trials, antibodies that cross-react with human insulin and insulin

glargine were observed with similar frequency in both treatment groups with

NPH insulin and insulin glargine in rare cases, the presence of such insulin antibodies may

the dosage of insulin to correct a tendency to hyper-or

hypoglycaemia.

Eye Disorders

A marked change in glycemic control may cause temporary visual impairment,

due to temporary alteration in the turgidity and refractive index of the lens.

Long-term improved glycemic control decreases the risk of progression of diabetic

retinopathy. Intensification of insulin therapy with abrupt improvement in

glycaemia, however, can also lead to temporary worsening of diabetic retinopathy.

In patients with proliferative retinopathy, particularly if not treated with photocoagulation,

severe hypoglycaemic episodes may result in transient amaurosis.

Skin and subcutaneous tissue disorders

As with any insulin therapy, injection site may occur

Local lipodystrophy and insulin absorption is delayed. Continuous rotation of

injection site within the given injection area may help to reduce

or prevent these reactions.

General disorders and administration site conditions

Reactions at the injection site redness, pain, itching, hives, swelling,

or inflammation. Most minor reactions to insulins at the injection site usually

pass a few days to several weeks.

Rarely, insulin may cause sodium retention and edema, particularly if previously poor

metabolic control is improved by intensified insulin therapy.

Paediatric population

In general, the safety profile in children and adolescents (<18 years) is similar to

safety profile in adults.

The adverse reactions obtained from postmarketing surveillance

included relatively more frequent injection site reactions (pain at the injection

location, injection-site reaction) and skin reactions (rash, urticaria) in children and

adolescents (<18 years) than in adults.

No safety data from clinical trials in children under 6 years.

 Overdose.

Symptoms

Insulin overdose may lead to severe and sometimes long-term and

life-threatening hypoglycemia.

Mastering

Mild episodes of hypoglycaemia can usually be treated with oral

carbohydrates. May need a dose adjustment of the drug product

diet or physical activity.

More severe episodes with coma, seizure, or neurologic impairment may be treated

intramuscular / subcutaneous glucagon or concentrated intravenous glucose. It may be

necessary Sustained carbohydrate intake and observation because hypoglycaemia may

recur after apparent clinical recovery.

 Pharmacological

 Pharmacokinetic properties:

In healthy subjects and diabetic patients, insulin serum concentrations indicated a slower and

more prolonged absorption and lack of a peak after subcutaneous injection of insulin

glargine compared with NPH human insulin. Thus, the concentrations are consistent with

time profile of the pharmacodynamic activity of insulin glargine above graph

shows the activity profiles over time of insulin glargine and NPH insulin.

Insulin glargine injected once daily will reach steady state levels in 2-4 days

after the first injection.

With intravenous injection, the half-life of insulin glargine and that of

human insulin are comparable.

In humans, insulin glargine is partly degraded in the subcutaneous tissue at the carboxyl terminus

the Beta chain with formation of active metabolites 21A-Gly-insulin and 21A-Gly-des-30B-

Thr-insulin. In plasma also Unchanged insulin glargine and products

breakdown.

In clinical studies, subgroup analyzes based on age and sex showed no differences

regarding safety and efficacy in patients treated with insulin glargine and

entire study population.

Paediatric population

There is no specific pharmacokinetic study conducted in children or adolescents.

 Pharmacodynamic properties:

 Pharmacotherapeutic group: Drugs used in diabetes. Insulins and analogues for injection, long-acting.

 ATC code: A10AE04

Insulin glargine is a human insulin analogue with low solubility at neutral pH.

In acidic Lantus injection solution (pH 4) is soluble. After injection into

subcutaneous tissue, the acidic solution is neutralized leading to formation of

micro-which constantly released small amounts of insulin glargine

providing a smooth, without peaks, predictable concentration / time profile with extended

duration.

Insulin receptor binding: Insulin glargine is very similar to human insulin

on the kinetics of insulin receptor binding. Therefore, it is assumed that by

Insulin receptors mediate the same type of effect as insulin.

The primary activity of insulin, including insulin glargine, is regulation

glucose metabolism. Insulin and its analogues lower blood glucose levels by

stimulating peripheral glucose uptake, especially by skeletal muscle and

fat, and by inhibiting hepatic glucose production. Insulin inhibits

lipolysis in the adipocyte, inhibits proteolysis and enhances protein synthesis.

The prolonged effect of subcutaneous insulin glargine is directly linked to the

slower rate of absorption and supports once daily administration. Time

action of insulin and insulin analogues such. Insulin glargine can significantly

vary in different individuals or within the same individual.

Preclinical safety data

Preclinical data reveal no special hazard for humans based on conventional

pharmacology, repeated dose toxicity,

genotoxicity, carcinogenicity, and reproductive toxicity.

PHARMACEUTICAL PARTICULARS

 List of excipients and their amounts

Zinc chloride

m-cresol

glycerol,

hydrochloric acid,

sodium hydroxide

water for injections.

 Incompatibilities

This medicinal product must not be mixed with other medicinal products. It is important to

ensure that syringes do not contain traces of any other material.

  Expiration date

2 years. Shelf life after first use of the vial medicinal product can be stored for a maximum of 4 weeks not above 25 ° C and away from direct heat or direct sunlight. Keep the vial in the outer carton to protect from light. It is recommended that the date of first use be noted on the label.

  Special precautions for storage

Unopened vials

Store in a refrigerator (2 ° C - 8 ° C).

Do not freeze.

Lantus not place near the freezer compartment or a freezer pack.

Keep the vial in the outer carton to protect from light.