Lantus SoloStar, 100 iu/ml 3 ml cartridges in syringe pens 5 pcs

Pharmacodynamics

Insulin Glargin is an analog of human insulin obtained by recombination of DNA-bacteria species of Escherichia coli (strain K12).

Insulin glargine is designed as an analogue of human insulin with low solubility in a neutral medium. In Lantus® SoloStar® it is fully soluble, which is ensured by the acidic reaction of the injection solution (pH 4). After injection into the subcutaneous fat, the acidic reaction of the solution is neutralized, resulting in the formation of microprecipitates from which small amounts of insulin glargin are continuously released, providing a predictable, smooth (no peaks) concentration-time curve profile and prolonged action of the drug.

Insulin glargine is metabolized to the two active metabolites M1 and M2 (see Pharmacokinetics).

Binding to insulin receptors: The kinetics of binding to specific insulin receptors in insulin glargin and its metabolites – M1 and M2 – are very similar to those of human insulin, so that insulin glargin is able to have a biological effect similar to that of endogenous insulin.

The most important action of insulin and its analogues, including insulin glargin, is regulation of glucose metabolism. Insulin and its analogues decrease blood glucose concentration by stimulating glucose uptake by peripheral tissues (especially skeletal muscle and adipose tissue) and inhibiting glucose formation in the liver.

Insulin suppresses lipolysis in adipocytes and inhibits proteolysis while increasing protein synthesis.

The prolonged action of insulin glargine is directly related to its reduced rate of absorption, which allows the drug to be used once a day. After p / n injection the onset of its action occurs on average in 1 hour. Average duration of action is 24 hours, maximum – 29 hours. Duration of action of insulin and its analogues such as insulin glargine may vary considerably in different persons or in the same person.

The efficacy of Lantus® SoloStar® has been shown in children over 2 years of age with type 1 diabetes. And in children aged 2-6 years, the incidence of hypoglycemia with clinical manifestations when using insulin glargine was lower both during the day and at night compared to the use of insulin isophan (respectively, an average of 25.5 episodes versus 33 episodes per patient for one year). In a five-year follow-up of patients with type 2 diabetes, there were no significant differences in the progression of diabetic retinopathy with treatment with insulin glargine compared to insulin isophane.

Binding to insulin-like growth factor 1 (IGF-1) receptors: The affinity of insulin glargine for the IGF-1 receptor is about 5-8 times higher than that of human insulin (but about 70-80 times lower than that of IGF-1), while, compared with human insulin, insulin glargine metabolites M1 and M2 have slightly lower affinity for the IGF-1 receptor.

The total therapeutic concentration of insulin (insulin glargine and its metabolites) determined in patients with type 1 diabetes was markedly lower than the concentration required for half-maximal binding to IGF-1 receptors and subsequent activation of the mitogen-proliferative pathway triggered via IGF-1 receptors. Physiological concentrations of endogenous IGF-1 can activate the mitogen-proliferative pathway; however, therapeutic insulin concentrations determined with insulin therapy, including treatment with Lantus® SoloStar®, are significantly lower than the pharmacological concentrations necessary to activate the mitogen-proliferative pathway.

The ORIGIN (Outcome Reduction with Initial Glargine INtervention) study was an international, multicenter, randomized study conducted in 12537 patients at high risk for cardiovascular disease and with impaired fasting glycemia (LPG), impaired glucose tolerance (IGT) or early-stage type 2 diabetes. Study participants were randomized into groups (1:1): a group of patients receiving insulin glargine (n=6264), which was titrated until reaching a fasting blood glucose concentration (BGC) ≤5.3 mmol, and a group of patients receiving standard treatment (n=6273). The first endpoint of the study represented the time to development of cardiovascular death, the first development of nonfatal myocardial infarction or nonfatal stroke, and the second endpoint represented the time to the first occurrence of any of the complications listed above or to the revascularization procedure (coronary, carotid or peripheral arteries) or to hospitalization for the development of heart failure.

The secondary endpoints were all-cause mortality and combined microvascular outcomes. The ORIGIN study showed that treatment with insulin glargine compared with standard hypoglycemic therapy did not alter the risk of cardiovascular complications or cardiovascular mortality; there were no differences in any component of the end points, all-cause mortality, combined microvascular outcome measures.

At baseline, the median HbA1c value was 6.4%. Median HbA1c values during treatment ranged from 5.9-6.4% in the insulin glargine group and 6.2-6.6% in the standard treatment group over the entire follow-up period. The incidence of severe hypoglycemia was 1.05 episodes per 100 patient-years of therapy in the patient group receiving insulin glargine and 0.3 episodes per 100 patient-years of therapy in the patient group receiving standard hypoglycemic therapy. The incidence of nonsevere hypoglycemia was 7.71 episodes per 100 patient-years of therapy in the group of patients receiving insulin glargine and 2.44 episodes per 100 patient-years of therapy in the group of patients receiving standard hypoglycemic therapy. In the 6-year study, 42% of patients in the group receiving insulin glargine had no episodes of hypoglycemia.

The median change in body weight versus outcome at the last treatment visit was 2.2 kg higher in the insulin glargine group than in the standard treatment group.

Pharmacokinetics
. A comparative study of plasma concentrations of insulin glargine and insulin isophan in healthy subjects and patients with diabetes mellitus after a single injection revealed slower and significantly longer absorption and no peak concentration in insulin glargine compared to insulin isophan. With a single daily infusion of Lantus® SoloStar®, the Css of insulin glargine in the blood is reached after 2-4 days with daily infusion.

In intravenous administration, the T1/2 of insulin glargine and human insulin were comparable. No significant differences in serum insulin concentrations were found when insulin glargine was injected into the abdomen, upper arm or thigh. Compared with human insulin of medium duration of action, insulin glargine is characterized by less variability in pharmacokinetic profile, both in the same and in different patients. In humans, insulin glargin is partially cleaved at the carboxyl end (C-end) side of the β-chain (beta-chain) to form two active metabolites M1 (21A G1u-insulin) and M2 (21A G1u-des-30B-Thg-insulin) in the subcutaneous fatty tissue. Metabolite M1 predominantly circulates in blood plasma. Systemic exposure to M1 metabolite increases with increasing drug dose.

Comparing pharmacokinetic and pharmacodynamic data showed that the drug action is mainly due to systemic exposure of M1 metabolite. In the vast majority of patients, insulin glargine and M2 metabolite could not be detected in the systemic bloodstream. In cases where insulin glargine and M2 metabolite were detected in the blood, their concentrations were independent of the dose of Lantus® SoloStar® administered.

Special patient groups

Age and sex. There is no information on the effect of age and sex on the pharmacokinetics of insulin glargine. However, these factors did not cause differences in the safety and efficacy of the drug.

Smoking. In clinical trials, subgroup analysis showed no differences in safety and efficacy of insulin glargine for this patient group compared to the general population.

Obesity. No differences in safety and efficacy of insulin glargine and insulin isophan were shown in obese patients compared to patients with normal body weight.

Children. In children with type 1 diabetes between 2 and 6 years of age, plasma concentrations of insulin glargine and its major metabolites M1 and M2 before the next dose were similar to those in adults, indicating no accumulation of insulin glargine and its metabolites with continued use of insulin glargine in children.

Indications

Diabetes mellitus requiring insulin treatment in adults, adolescents, and children over 2 years of age.

Active ingredient

Insulin glargine

Composition

Active ingredient: insulin glargine 100 IU (3.6378 mg)

Excipients: methacresol (m-cresol), 2.7 mg; zinc chloride, 0.0626 mg (corresponding to 30 µg of zinc); glycerol (85%), 20 mg; sodium hydroxide, to pH 4; hydrochloric acid, to pH 4; water for injection, to 1 ml.

How to take, the dosage

P/k. Adults and children over 2 years of age.

General recommendations

Lantus® SoloStar® should be given p/k once daily at any time, but at the same time every day.

Lantus® SoloStar®

Patients with type 1 diabetes. Lantus® SoloStar® should be used once daily in combination with insulin administered at meal times with individual dose adjustment.

Patients with type 2 diabetes mellitus. In patients with type 2 diabetes mellitus, Lantus® SoloStar® may be used both as monotherapy and in combination with other hypoglycemic drugs.

The target values of blood glucose concentrations, as well as doses and times of administration or administration of hypoglycemic drugs must be determined and adjusted individually.

Dose adjustments may also be necessary, for example, if the patient’s body weight, lifestyle, timing of insulin dosing, or other conditions may increase the predisposition to develop hypo- or hyperglycemia (see “Special Instructions”). Any changes in insulin dose should be made with caution and under medical supervision.

Lantus® SoloStar® is not the insulin of choice for the treatment of diabetic ketoacidosis. In this case, intravenous short-acting insulin should be preferred.

In treatment regimens that include basal and prandial insulin injections, 40-60% of the daily insulin dose is usually administered as insulin glargine to meet the basal insulin requirement.

In patients with type 2 diabetes using oral hypoglycemic medications, combination therapy begins with a dose of insulin glargine 10 units once daily, and the regimen is adjusted individually thereafter.

In all patients with diabetes mellitus, monitoring of blood glucose concentrations is recommended.

Transfer from treatment with other hypoglycemic drugs to Lantus® SoloStar®

. When a patient is switched from a medium- or long-acting insulin regimen to Lantus® SoloStar® treatment, adjustments in the number (doses) and timing of daily doses of short-acting insulin or its analogues or changes in the doses of oral hypoglycemic drugs may be required.

Transfer from once daily administration of isophan insulin to Lantus® SoloStar®

Transferring patients from once daily administration of isophan insulin to once daily administration of Lantus® SoloStar® usually does not change the starting doses of insulin (i.e., the number of units/day is used).i.e., the number of IU/day of Lantus® SoloStar® is the same as the number of IU/day of insulin-isophane.)

Transfer from twice-daily insulin-isophan to Lantus® SoloStar®

Transfer patients from twice-daily insulin-isophan to Lantus® SoloStar®. When patients are switched from twice-daily insulin-isophane to a single dose of Lantus® SoloStar® before bed to reduce the risk of hypoglycemia at night and in the early morning hours, the initial daily dose of insulin glargine is usually reduced by 20% (compared to the daily insulin-isophane dose) and then adjusted according to patient response.

The switch from Tugeo SoloStar® (insulin glargine 300 units/ml) to Lantus® SoloStar®

Insulin glargine 100 units/ml and Tugeo SoloStar® are not equivalent in their pharmacokinetic, pharmacodynamic characteristics and clinical effects. Therefore, switching from Tugeo SoloStar® to insulin glargine 100 units/ml and vice versa requires medical supervision, careful metabolic monitoring, and individual adjustment of the drug dose. In order to reduce the risk of hypoglycemia when transferring patients from a single daily dose of Tugeo SoloStar® (insulin glargine 300 units/ml) to a single daily dose of Lantus® SoloStar®, the recommended initial dose of Lantus® SoloStar® should be decreased by about 20%. During the first weeks of treatment, this reduction of Lantus® SoloStar® dose can be partially compensated by increasing the prandial insulin dose. At the end of this period, the treatment regimen should be adjusted on an individual basis. During transfer to another treatment regimen and for the next few weeks it is recommended to perform close metabolic monitoring (control of blood glucose concentration) under medical supervision, with adjustment of insulin dosing regimen if necessary.

As with all human insulin analogues, this is especially important for patients who require high doses of human insulin because they have antibodies to human insulin. In such patients, a significant improvement in insulin response may be observed with glargine insulin. If metabolic control improves and the resulting increase in tissue sensitivity to insulin, the insulin dosing regimen may need to be adjusted.

Mixing and Dilution

Lantus® SoloStar® should not be mixed with other insulins. Mixing can change the time action profile (time/action ratio) of Lantus® SoloStar® and can lead to precipitation.

Lantus® SoloStar® must not be diluted. Dilution can cause a change in the drug’s action profile over time.

Special patient groups

Children. Lantus® SoloStar® can be used in children over 2 years of age. The use in children younger than 2 years old has not been studied.

Patients in the elderly. In elderly patients with diabetes mellitus, a moderate initial dose, a slow increase in dose, and the use of moderate maintenance doses are recommended. In elderly patients it may be difficult to recognize the developing hypoglycemia (see “Cautionary Note”). Close monitoring of blood glucose concentration with individual selection of insulin dose is recommended. In elderly patients, progressive deterioration of renal function may lead to a permanent reduction of insulin requirement.

Patients with renal insufficiency. Insulin glargine may be used in patients with renal insufficiency, and close monitoring of blood glucose concentrations with individual dose adjustment is recommended. In patients with renal insufficiency the need for insulin may decrease due to slower insulin metabolism.

Patients with hepatic impairment. Insulin glargine may be used in patients with hepatic insufficiency, at the same time close monitoring of blood glucose concentration with individual selection of dose is recommended. In patients with hepatic insufficiency, insulin requirement may decrease due to decrease in gluconeogenesis and slowing down of insulin metabolism.

C To use Lantus® SoloStar®

The drug Lantus® SoloStar® is administered as a p/u injection. It is not intended for intravenous administration. Long duration of action of insulin glargine is observed only when injected into the subcutaneous fatty tissue. IV administration of a normal subcutaneous dose may cause severe hypoglycemia. Lantus® SoloStar® should be injected into the subcutaneous fatty tissue of the abdomen, shoulders or thighs. The injection sites should alternate with each new injection within the recommended areas for p/u administration.

As with other types of insulin, the degree of absorption and therefore onset and duration of action may be affected by exercise and other changes in the patient’s condition.

Lantus® SoloStar® is a clear solution, not a suspension. Therefore, resuspension is not required prior to use.

If the Lantus® SoloStar® syringe fails, the insulin glargine can be removed from the cartridge into a syringe (suitable for 100 IU/ml insulin) and the desired dose of product injected. The syringe must be free of residues of other drugs.

The needles must not be reused. A new sterile needle should be attached before each injection. Repeated use of needles increases the risk of needle blockage, which can lead to a lower dose or overdose. Using a new sterile needle for each injection minimizes the risk of contamination and infection. To avoid possible transmission of blood-borne diseases, insulin syringe pens should not be used by more than one patient, even if the needle is replaced. Before each injection, the label on the syringe pen should be checked and the date of first use should be given.

Patient Instructions

The instructions for use and handling of the pre-filled SoloStar® syringe pen

The syringe pen must be kept at room temperature for 1-2 hours before first use.

The cartridge inside the syringe pen should be inspected before use. It should only be used if the solution is clear, colorless, contains no visible particulates, and has the consistency of water.

The empty SoloStar® syringe pens should not be reused and should be destroyed.

In order to prevent infection, the pre-filled syringe pen should only be used by one patient and not given to another person.

The handling of the SoloStar® syringe pen

Please read the information for use carefully before using the SoloStar® syringe pen.

Important information about the use of the SoloStar® Syringe Pen

We should carefully connect a new needle to the syringe pen and perform a safety test before each use.Only needles compatible with SoloStar® that are purchased separately should be used.

Particular precautions must be taken to avoid needlestick-related accidents and the possibility of infection transfer.

The SoloStar® syringe pen should never be used if it is damaged or if it is not certain that it will work properly.

You should always have a spare SoloStar® syringe pen in case you lose or damage your previous copy of the SoloStar® syringe pen.

Storage instructions

The section “Storage conditions” should be read for the SoloStar® Syringe pen.

If the SoloStar® syringe is stored in a refrigerator, remove it 1-2 hours before the intended injection to allow the solution to come to room temperature. Injection of refrigerated insulin is more painful.

The used SoloStar® syringe pen must be destroyed.

Operation

The SoloStar® syringe pen must be protected from dust and dirt.

The outside of the SoloStar® syringe pen can be cleaned by wiping it with a damp cloth.

The SoloStar® Syringe must not be soaked, rinsed, or lubricated as this can damage the SoloStar® Syringe.

The SoloStar® Syringe pen dispenses insulin accurately and is safe to use. It also requires gentle handling. Avoid situations where the SoloStar® syringe pen can be damaged. If you suspect that the SoloStar® syringe is damaged, you should use a new syringe pen.

Stage 1. Insulin control

The label on the SoloStar® syringe pen should be checked to make sure it contains the appropriate insulin. For Lantus®, the SoloStar® syringe pen is gray with a purple injection button. After removing the syringe cap, check the appearance of the insulin in the pen: the insulin solution should be clear, colorless, without any visible solid particles and should have a water-like consistency.

Step 2. Connecting the needle

Please only use needles that are compatible with the SoloStar® syringe pen.

A new sterile needle is always used for each subsequent injection. The needle must be carefully placed on the syringe pen after the cap is removed.

Stage 3. Performing a safety test

Before each injection, a safety test must be performed to ensure that the syringe pen and needle are working well and that air bubbles have been removed.

A dose equal to 2 units is measured.

The outer and inner needle caps must be removed.

Positioning the syringe pen with the needle up, gently tap the insulin cartridge with your finger so that any air bubbles are directed toward the needle.

The injection button is fully depressed.

If the insulin appears at the tip of the needle, it means that the syringe pen and needle are working correctly.

If there is no insulin at the tip of the needle, then stage 3 can be repeated until there is no insulin at the tip of the needle.

Stage 4. Dose Selection

The dose can be set to the nearest 1 IU, from the lowest dose (1 IU) to the highest dose (80 IU). If a dose greater than 80 IU is to be administered, 2 or more injections should be made.

The dosage window should show “0” after completing the safety test. The desired dose can then be set.

Stage 5. Dose administration

The patient must be informed of the injection technique by the healthcare provider.

The needle must be inserted under the skin.

The injection button must be fully pressed. It is held in this position for an additional 10 seconds before the needle is withdrawn. This ensures that the selected dose of insulin is injected completely.

Stage 6. Removing and discarding the needle

In all cases, the needle must be removed and discarded after each injection. This prevents contamination and/or infection, air entering the insulin reservoir and insulin leakage.

Special precautions must be taken when removing and discarding the needle. Recommended safety precautions for removing and discarding needles (e.g., one-handed cap technique) must be followed to reduce the risk of needlestick-related accidents, as well as to prevent infection.

After removing the needle, the SoloStar® syringe pen should be capped.

Interaction

Peroral hypoglycemic agents, ACE inhibitors, disopyramide, fibrates, fluoxetine, MAO inhibitors, pentoxifylline, propoxyphene, salicylates and sulfonamide antimicrobials – may increase the hypoglycemic effect of insulin and increase the predisposition to hypoglycemia. Concomitant use with insulin glargine may require adjustment of the insulin dose.

. GCS, danazol, diazoxide, diuretics, glucagon, isoniazid, estrogens and gestagens (such as in hormonal contraceptives), phenothiazine derivatives, somatotropin, sympathomimetics (such as epinephrine, salbutamol, terbutaline) and thyroid hormones, protease inhibitors, atypical neuroleptics (e.g., olanzapine or clozapine) may impair the hypoglycemic effects of insulin. Simultaneous use with insulin glargine may require adjustment of the dose of insulin glargine.

Beta-adrenoblockers, clonidine, lithium salts, or alcohol may both enhance and weaken the hypoglycemic effects of insulin.

Pentamidine – when combined with insulin may cause hypoglycemia, which sometimes changes to hyperglycemia.

Sympatholytic drugs such as beta-adrenoblockers, clonidine, guanethidine and reserpine – may reduce or lack signs of adrenergic counterregulation (sympathetic nervous system activation) in the development of hypoglycemia.

Pharmaceutical Interactions

Lantus® SoloStar® may precipitate or change the action profile of the drug over time when mixed with other drugs, including other insulins.

Special Instructions

Lantus® SoloStar® is not the drug of choice for the treatment of diabetic ketoacidosis. In such cases, intravenous short-acting insulin is recommended.

In view of limited experience with Lantus® SoloStar®, it has not been possible to evaluate its efficacy and safety in patients with hepatic impairment or with moderate or severe renal impairment.

In patients with impaired renal function, the need for insulin may decrease due to slower elimination. In elderly patients, progressive deterioration of renal function may lead to persistent reduction of insulin requirement.

In patients with severe hepatic insufficiency, the need for insulin may be reduced due to decreased gluconeogenesis capacity and delayed insulin biotransformation.

If blood glucose levels are insufficiently controlled or if there is a tendency toward hypo- or hyperglycemia, accurate adherence to the prescribed regimen, adherence to the site of administration, and correct technique of injection should be checked before initiating dosing adjustment, taking all influencing factors into account.

Hypoglycemia

The timing of hypoglycemia depends on the profile of action of the insulins used and may thus change with treatment regimen. Due to the increased time of long-acting insulin intake with Lantus® SoloStar®, a lower probability of nighttime hypoglycemia should be expected, whereas this probability of hypoglycemia is higher in the early morning hours. If hypoglycemia occurs in patients receiving Lantus® SoloStar®, the possibility of delayed recovery from hypoglycemia due to the prolonged action of glargine insulin should be considered.

. Patients in whom episodes of hypoglycemia may be of particular clinical significance, such as patients with severe stenosis of coronary arteries or cerebral vessels (risk of cardiac and cerebral complications of hypoglycemia), and patients with proliferative retinopathy, especially if they are not receiving photocoagulation treatment (risk of transient vision loss following hypoglycemia) should exercise particular caution and intensify monitoring of blood glucose.

Patients should be warned about conditions in which hypoglycemia precursor symptoms may decrease. In patients in certain at-risk groups, symptoms of hypoglycemia may change, become less severe, or be absent. These include:

Patients in whom blood glucose regulation has improved markedly;

Patients in whom hypoglycemia develops gradually;

– elderly patients;

– patients who have switched from animal insulin to human insulin;

Patients with neuropathy;

Patients with a long history of diabetes mellitus;

Patients with psychiatric disorders;

Patients receiving concomitant treatment with other medications (see “Interactions”).

These situations can lead to severe hypoglycemia (with possible loss of consciousness) before the patient realizes that he or she is developing hypoglycemia.

If normal or reduced glycosylated Hb values are noted, the possibility of recurrent unrecognized episodes of hypoglycemia (especially at night) should be considered.

Patient compliance with dosing and feeding regimens, proper insulin administration, and knowledge of hypoglycemic precursor symptoms all contribute to significantly reducing the risk of hypoglycemia.

Factors that increase the propensity for hypoglycemia that require particularly close monitoring and may require insulin dose adjustments:

– change in location of insulin administration;

– increased insulin sensitivity (e.g., when stressors are removed);

– Unusual, increased or prolonged physical activity;

– Intercurrent illness with vomiting, diarrhea;

– disorder of diet and eating habits;

– missing a meal;

– alcohol consumption;

– Certain uncompensated endocrine disorders (e.g., hypothyroidism, adenohypophysis or adrenal cortex insufficiency);

– concomitant treatment with certain medications (see “Interactions. “Interactions”).

Intercurrent diseases

In intercurrent diseases more intensive control of blood glucose levels is required. In many cases, urinalysis for ketone bodies is indicated, and adjustments to insulin dosing regimen are also often required. The need for insulin often increases. Type 1 diabetics should continue regular intake of at least small amounts of carbohydrates, even if they are only able to eat small amounts or cannot eat at all, or have vomiting, etc., and they should never stop insulin administration altogether.

Principles for Handling

When storing Lantus® SoloStar® in the refrigerator, care should be taken to ensure that containers do not come into direct contact with the freezer compartment or frozen packs.

The Lantus® SoloStar® syringe should be kept at room temperature for 1-2 hours before first use.

The used single-use SoloStar® syringe pens should be stored at a temperature no higher than 30 °C, protected from light.

Prefilled SoloStar® syringe pens should not be refrigerated.

The shelf life of the drug in the SoloStar® disposable syringe pen after first use is 4 weeks. It is recommended that the date of the first administration be noted on the label.

Impact on the ability to drive vehicles, machinery. Patients’ ability to concentrate and quick psychomotor reaction may be impaired by conditions such as hypoglycemia, hyperglycemia or visual disturbances. This may pose a risk in situations where these abilities are particularly important (e.g., driving a car or operating other mechanisms). Patients are advised to take precautions to avoid developing hypoglycemia while driving. This is especially important for those patients who have little or no symptoms that are precursors of developing hypoglycemia, or for patients with frequent occurrence of hypoglycemia. Such circumstances should be considered when driving.

Synopsis

Transparent, colorless or nearly colorless liquid.

Contraindications

Hypersensitivity to insulin glargine or any of the excipients of the drug;

Children under 2 years of age (no clinical data on its use).

With caution: pregnant women (possibility of changes in the need for insulin during pregnancy and after delivery).

Side effects

The following adverse effects are given by organ system according to the following frequency gradations (according to MedDRA classification): very common – ≥10%; common – ≥1-< 10%; infrequent – ≥0.1-< 1%; rare – ≥0.01-< 0.1%; very rare – ≤0.01%.

Metabolic side:very often – hypoglycemia. Hypoglycemia, the most common adverse reaction in insulin therapy, can occur if the dose of insulin is too high compared to the need for it.

The symptoms of hypoglycemia usually occur suddenly. However, often neuropsychiatric disorders against the background of neuroglycopenia (feeling of fatigue, unusual fatigue or weakness, decreased ability to concentrate, drowsiness, visual disturbances, headache, nausea, confusion or loss of consciousness, seizure syndrome) are usually preceded by symptoms of adrenergic counterregulation (sympathoadrenal system activation in response to hypoglycemia) – hunger, irritability, nervous agitation or tremor, anxiety, pale skin, cold sweat, tachycardia, palpitations (the faster hypoglycemia develops and the more severe it is, the more pronounced are symptoms of adrenergic counterregulation).

Eps of severe hypoglycemia, especially repeated, may lead to damage of the nervous system. Episodes of prolonged and severe hypoglycemia may be life-threatening for patients, as even a fatal outcome is possible if hypoglycemia worsens.

Some immune system disorders: rare – allergic reactions. Immediate allergic reactions to insulin are rare. Such reactions to insulin (including insulin glargine) or excipients may manifest as the development of generalized skin reactions, angioedema, bronchospasm, arterial hypotension or shock and thus may be life-threatening for the patient.

The use of insulin may cause the formation of antibodies to it. The formation of antibodies that cross-react with human insulin and insulin glargine is observed with equal frequency with isophan and glargine insulin. In rare cases, the presence of these insulin antibodies may necessitate adjustments to the dosing regimen to eliminate the tendency to develop hypo- or hyperglycemia.

Nervous system disorders:very rarely, dysgeusia (impairment or perversion of the sense of taste).

Visual organ: rarely – visual disturbances, retinopathy.

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

Long-term normalization of blood glucose decreases the risk of progression to diabetic retinopathy. Insulin therapy with abrupt fluctuations in blood glucose may be accompanied by a temporary worsening of the course of diabetic retinopathy. In patients with proliferative retinopathy, especially those not treated with photocoagulation, episodes of severe hypoglycemia may lead to the development of transient vision loss.

Skin and subcutaneous fat:often – lipodystrophy (in 1-2% of patients). As with the treatment with any other insulin drugs, lipodystrophy may develop at the injection site, which may slow local absorption of insulin; infrequently – lipoatrophy. Constant change of injection sites within the areas of the body recommended for p/k insulin administration may help to reduce the severity of this reaction or prevent its development.

Musculoskeletal and connective tissue disorders:very rarely – myalgia.

General disorders and reactions at the site of administration: often – reactions at the site of administration (3-4%) (redness, pain, itching, urticaria, swelling or inflammation). Most minor reactions at the injection site usually resolve within a period of several days to several weeks; rarely – sodium retention, edema (especially if intensified insulin therapy leads to improvement of previously insufficient metabolic control).

The safety profile for patients younger than 18 years is generally similar to that for patients older than 18 years. Patients younger than 18 years are relatively more likely to have injection site reactions and skin reactions (rash, urticaria).

There are no safety data available in patients younger than 2 years of age.

Overdose

Insulin overdose can lead to severe and sometimes prolonged hypoglycemia, threatening the life of the patient.

Treatment: Episodes of moderate hypoglycemia are usually controlled by oral administration of rapidly digestible carbohydrates. It may be necessary to change the dosing regimen of the drug, diet, or physical activity.

Episodes of more severe hypoglycemia manifested by coma, seizures or neurological disorders require intravenous or intravenous glucagon administration and intravenous injection of concentrated dextrose (glucose) solution. Prolonged carbohydrate administration and monitoring by a specialist may be necessary, since after visible clinical improvement, a relapse of hypoglycemia is possible.

Pregnancy use

Patients should inform their physician of a current or planned pregnancy.

There have been no randomized controlled clinical trials on the use of insulin glargine in pregnant women.

A large number of observational studies (more than 1,000 pregnancy outcomes in retrospective and prospective follow-up) in the postmarketing use of insulin glargine have shown it to have no specific effects on the course and outcome of pregnancy or on fetal or neonatal health.

In addition, a meta-analysis of eight observational clinical trials that included women who used insulin glargine (n=331) and insulin isophane (n=371) during pregnancy was conducted to assess the safety of insulin glargine and insulin isophane in pregnant women with pre-existing or gestational diabetes. This meta-analysis found no significant differences regarding maternal or neonatal health safety when insulin glargine and insulin isophane were used during pregnancy.

There was no direct or indirect evidence of embryotoxic or fetotoxic effects of insulin glargin in animal studies.

For patients with pre-existing or gestational diabetes, it is important to maintain adequate metabolic regulation throughout pregnancy to prevent adverse outcomes associated with hyperglycemia.

Lantus® SoloStar® may be used in pregnancy for clinical indications.

The insulin requirement may decrease in the first trimester of pregnancy and generally increase during the second and third trimesters.

Immediately after delivery, the need for insulin decreases rapidly (increased risk of hypoglycemia). Under these conditions, careful monitoring of blood glucose concentrations is essential.

Patients who are breastfeeding may need to adjust their insulin dosing regimen and diet.

Similarities

Tugeo SoloStar