Lantus® solostar®

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT LANTUS® SoloStar®

Composition:

Active substance: insulin glargine;

1 ml of injection solution contains 3.6378 mg of insulin glargine, equivalent to 100 IU of insulin glargine;

1 cartridge contains 3 ml of injection solution, corresponding to 300 IU of insulin glargine;

Excipients: zinc chloride, m-cresol, glycerol (85%), hydrochloric acid concentrated, sodium hydroxide, water for injections.

Pharmaceutical form. Solution for injection.

Main physicochemical properties: colorless or almost colorless clear solution.

Pharmacotherapeutic group. Long-acting insulins and analogues for injection.

ATC code A10AE04.

Pharmacological properties.

Pharmacodynamics.

Insulin glargine is designed as an analogue of human insulin with low solubility in a neutral environment. In the Lantus***®*** SoloStar® formulation, it is completely soluble due to the acidic pH of the injection solution (pH 4). After subcutaneous injection, the acidic solution is neutralized, leading to the formation of microprecipitates from which a small amount of insulin glargine is continuously released. This provides a smooth (peakless) and predictable concentration–time profile and a longer duration of action.

Insulin glargine is metabolized into two active metabolites – M1 and M2 (see section "Pharmacokinetics").

Binding to the insulin receptor:

In vitro studies indicate that the affinity of insulin glargine and its metabolites M1 and M2 for the human insulin receptor is similar to that of human insulin.

Binding to the IGF-1 receptor (insulin-like growth factor 1):

The affinity of insulin glargine for the IGF-1 receptor is approximately 5–8 times higher than that of human insulin (but still about 70–80 times lower than the affinity of IGF-1 for this receptor), whereas metabolites M1 and M2 bind to the IGF-1 receptor with affinity slightly lower than that of human insulin.

The total therapeutic concentration of insulin (insulin glargine and its metabolites) observed in patients with type 1 diabetes was significantly lower than the concentration required for half-maximal binding to the IGF-1 receptor and subsequent activation of the mitogenic-proliferative pathway mediated by the IGF-1 receptor. Endogenous IGF-1 can activate the mitogenic-proliferative pathway at physiological concentrations; however, therapeutic insulin concentrations used in insulin therapy, including therapy with Lantus***®*** SoloStar®, are substantially lower than the pharmacological concentrations needed to activate the IGF-1-mediated mechanism.

The most important action of insulin, including insulin glargine, is the regulation of glucose metabolism. Insulin and its analogues reduce blood glucose levels by stimulating glucose uptake in peripheral tissues, particularly skeletal muscle and adipose tissue, and by suppressing glucose production in the liver. Insulin inhibits lipolysis in adipocytes and proteolysis, while simultaneously enhancing protein synthesis.

Clinical-pharmacological studies have demonstrated equivalence of equal doses of insulin glargine and human insulin after intravenous administration. As with any insulin, the time course of insulin glargine’s action may be influenced by physical activity and other factors.

Euglycemic clamp studies conducted in healthy volunteers and patients with type 1 diabetes have shown that, unlike human NPH (neutral protamine Hagedorn) insulin, insulin glargine has a delayed onset of action after subcutaneous injection, acts smoothly without producing peaks in glucose-lowering effect, and has a prolonged duration of action.

Results from one study in patients are shown in the graph below.

Activity profile in patients with type 1 diabetes.

Time (hours) elapsed after subcutaneous injection

End of observation period

* Defined as the amount of glucose infused to maintain a steady plasma glucose level (hourly mean values).

The longer duration of action of subcutaneously administered glargine insulin is directly related to its slower absorption, allowing once-daily administration. The time-action profile of insulin and its analogs, such as insulin glargine, may exhibit considerable inter-individual and intra-individual variability.

In a clinical trial following intravenous administration of insulin glargine and human insulin, symptoms of hypoglycemia or hormonal counter-regulatory responses were similar in healthy volunteers and patients with type 1 diabetes mellitus.

The effect of insulin glargine (administered once daily) on the progression of diabetic retinopathy was evaluated in an open-label five-year trial, in which the comparator was NPH insulin (administered twice daily), involving 1024 patients with type 2 diabetes who experienced progression of retinopathy by 3 or more steps on the scale used in the Early Treatment Diabetic Retinopathy Study (ETDRS). Progression was assessed using fundus photography. No statistically significant difference in progression of diabetic retinopathy was observed between insulin glargine (Lantus®) and NPH insulin.

The ORIGIN trial (Outcome Reduction with Initial Glargine INtervention) was a multicenter, randomized, 2 x 2 factorial-designed study involving 12,537 patients at high cardiovascular (CV) risk who had impaired fasting glucose (IFG) or impaired glucose tolerance (IGT) (12% of participants), or type 2 diabetes treated with ≤1 oral antidiabetic agent (88% of participants). Participants were randomized (1:1) to receive either insulin glargine (n=6264), with dose titrated to achieve fasting plasma glucose ≤95 mg/dL (5.3 mmol/L), or standard therapy (n=6273).

The primary composite endpoint consisted of time to first occurrence of CV death, non-fatal myocardial infarction (MI), or non-fatal stroke; the second component of the primary composite endpoint was time to first occurrence of any of these events or revascularization procedures (coronary, carotid, or peripheral vessels), or hospitalization for heart failure.

Secondary endpoints included all-cause mortality and a composite endpoint of microvascular events.

Insulin glargine did not alter the relative risk of CV disease or CV death compared to standard therapy. There were no differences between insulin glargine and standard therapy for either component of the primary composite endpoint, for any individual component of these adverse clinical outcomes, for all-cause mortality, or for the composite microvascular endpoint.

The mean insulin glargine dose at the end of the study was 0.42 IU/kg. At baseline, the mean HbA1c level among participants was 6.4%, and during the study treatment, HbA1c levels ranged from 5.9% to 6.4% in the insulin glargine group and from 6.2% to 6.6% in the standard therapy group throughout the observation period.

The incidence of severe hypoglycemia (expressed as number of participants experiencing such episodes per 100 patient-years of treatment) was 1.05 in the insulin glargine group and 0.30 in the standard therapy group, while the rate of confirmed non-severe hypoglycemic episodes was 7.71 in the insulin glargine group and 2.44 in the standard therapy group. During this 6-year study, 42% of patients in the insulin glargine group experienced no hypoglycemic episodes.

At the final visit on study treatment, body weight increased from baseline by a mean of 1.4 kg in the insulin glargine group and decreased by a mean of 0.8 kg in the standard therapy group.

Children and Adolescents

In a randomized controlled clinical trial, children (aged 6 to 15 years) with type 1 diabetes (n = 349) received insulin therapy in a basal-bolus regimen for 28 weeks, with regular human insulin administered before each meal. Insulin glargine was given once daily at night, and NPH insulin was administered once or twice daily. In both groups, the effect on glycated hemoglobin levels and the frequency of clinically manifested hypoglycemia were similar; however, the reduction in fasting plasma glucose from baseline was greater in the insulin glargine group compared to the NPH group. Additionally, the severity of hypoglycemia was lower in the insulin glargine group. 143 patients who received insulin glargine during this trial continued treatment with insulin glargine in an uncontrolled extension phase with a mean follow-up duration of 2 years. No new safety signals were observed during continued treatment with insulin glargine.

A crossover comparative study of insulin glargine plus insulin lispro versus NPH insulin plus regular human insulin (each treatment administered for 16 weeks in random order) was also conducted in 26 adolescents with type 2 diabetes aged 12 to 18 years. As in the previously described pediatric study, the reduction in fasting blood glucose from baseline was greater in the insulin glargine group compared to the NPH insulin/regular human insulin group. Changes in HbA1c levels from baseline were similar in both groups, but nocturnal glycemic values were significantly higher in the insulin glargine/insulin lispro group than in the NPH insulin/regular insulin group, with mean nadir values of 5.4 mM versus 4.1 mM, respectively. Consequently, the incidence of nocturnal hypoglycemia was 32% in the insulin glargine/insulin lispro group and 52% in the NPH insulin/regular insulin group.

A 24-week parallel-group study was conducted in 125 children with type 1 diabetes aged 2 to 6 years, comparing once-daily morning administration of insulin glargine versus one or two daily doses of NPH insulin as basal insulin. Participants in both study groups received bolus insulin injections before meals.

The primary objective of the study—to demonstrate that NPH insulin is at least non-inferior to insulin glargine regarding overall hypoglycemia risk—was not met, and a trend toward increased frequency of hypoglycemic events was observed with insulin glargine [rate ratio for insulin glargine:NPH (95% CI) = 1.18 (0.97–1.44)].

Changes in glycated hemoglobin and blood glucose levels were similar in both treatment groups. No new safety findings were observed in this study.

Pharmacokinetics.

Comparisons of insulin concentrations in serum between healthy volunteers and diabetic patients indicated slower and more prolonged absorption of insulin glargine, and demonstrated the absence of a concentration peak after subcutaneous injection of insulin glargine, in contrast to human NPH insulin. Thus, the observed insulin glargine concentrations fully corresponded to the time-action pharmacodynamic profile of the drug. The graph above illustrates the time-action profiles of insulin glargine and NPH insulin.

After once-daily administration, steady-state concentrations of insulin glargine are achieved within 2–4 days following the first injection.

Following intravenous administration, elimination half-lives of insulin glargine and human insulin are comparable.

After subcutaneous injection of Lantus® SoloStar® in patients with diabetes, insulin glargine is rapidly metabolized at the carboxy-terminus of the beta-chain, forming two active metabolites—M1 (21A-glycine-insulin) and M2 (21A-glycine-des-30B-threonine-insulin). In plasma, M1 is the predominant circulating compound. M1 exposure increases proportionally with the administered dose of Lantus® SoloStar®. Pharmacokinetic and pharmacodynamic data indicate that the effect of subcutaneous Lantus® SoloStar® injection is primarily related to M1 exposure. Insulin glargine and metabolite M2 were undetectable in most study participants, and when detectable, their concentrations were independent of the administered dose of Lantus® SoloStar®.

In clinical studies, subgroup analyses by age and gender showed no differences in safety and efficacy outcomes between patients receiving insulin glargine and the overall study population.

Children and Adolescents

The pharmacokinetics of the drug in children aged 2 to less than 6 years with type 1 diabetes was evaluated in one clinical study (see section "Pharmacodynamics"). Minimal levels of insulin glargine and its main metabolites (M1 and M2) were detected in plasma of children receiving insulin glargine. Concentration-time profiles were found to be similar to those in adults, and there was no evidence of accumulation of insulin glargine or its metabolites with long-term use.

Preclinical Safety Data

Preclinical data obtained from standard studies on pharmacological safety, repeated-dose toxicity, genotoxicity, carcinogenic potential, and reproductive toxicity revealed no special hazard to humans.

Clinical characteristics.

Indications.

Treatment of diabetes mellitus in adults, adolescents, and children aged 2 years and older.

Contraindications.

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

Interaction with other medicinal products and other forms of interaction.

There are several substances that affect glucose metabolism and, therefore, their use may require adjustment of glargine insulin dosage.

Substances that may enhance the hypoglycemic effect of insulin and increase the risk of hypoglycemia include oral antidiabetic medicinal products, angiotensin-converting enzyme (ACE) inhibitors, disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors (MAO), pentoxifylline, propoxyphene, salicylates, and sulfonamide antimicrobial agents.

Substances that may reduce the hypoglycemic effect of insulin include corticosteroids, danazol, diazoxide, diuretics, glucagon, isoniazid, estrogens and progestogens, phenothiazine derivatives, somatropin, sympathomimetic medicinal products (epinephrine (adrenaline), salbutamol, terbutaline), thyroid hormones, atypical antipsychotic medicinal products (e.g., clozapine and olanzapine), and protease inhibitors.

Beta-blockers, clonidine, lithium salts, or alcohol may either enhance or reduce the hypoglycemic effect of insulin. Pentamidine may cause hypoglycemia, which may sometimes be followed by hyperglycemia.

In addition, under the influence of sympatholytic agents such as beta-blockers, clonidine, guanethidine, and reserpine, the symptoms of adrenergic counter-regulation may be diminished or absent.

Special precautions.

Lantus® SoloStar® is not the drug of choice for the treatment of diabetic ketoacidosis. Intravenous administration of regular insulin is recommended in such cases.

If adequate control of glucose levels cannot be achieved or episodes of hypoglycemia or hyperglycemia occur during treatment, the patient's adherence to the prescribed treatment regimen, injection sites, proper injection technique, and other important factors affecting treatment efficacy should be evaluated before changing the drug dosage.

Switching a patient to another type or brand of insulin should be done under close medical supervision. Changes in strength, brand (manufacturer), type (regular, NPH, lente, long-acting, etc.), origin (animal, human, human insulin analog), and/or method of production may necessitate a change in insulin dosage.

Insulin administration may lead to the formation of insulin antibodies. In rare cases, the presence of insulin antibodies may require dose adjustment to prevent hypoglycemia or hyperglycemia (see section "Adverse reactions").

Patients should be advised to rotate injection sites regularly to reduce the risk of lipodystrophy and cutaneous amyloidosis. There is a potential risk of delayed insulin absorption and impaired glycemic control following insulin injections into areas affected by these reactions. Changing the injection site to an unaffected skin area has been reported to cause hypoglycemia. Glucose monitoring is recommended after changing the injection site, and dose adjustments of antidiabetic medications should be considered.

Hypoglycemia

The time of onset of hypoglycemia depends on the pharmacological profile of the insulin used and may therefore vary when changing treatment regimens. Due to the more stable delivery of basal insulin with Lantus® use, a lower likelihood of nocturnal hypoglycemia is expected, whereas hypoglycemia is more likely in the early morning hours.

Particular caution and intensified blood glucose monitoring are required in patients in whom hypoglycemic episodes may be especially dangerous from a clinical standpoint, such as patients with significant stenosis of coronary arteries or cerebral blood vessels (risk of cardiac or cerebral complications of hypoglycemia), as well as patients with proliferative retinopathy who have not undergone photocoagulation (risk of transient post-hypoglycemic blindness).

Patients should be aware that under certain circumstances, early symptoms of hypoglycemia may be less pronounced. Signs indicating the development of hypoglycemia may change, become less evident, or even be absent in patients belonging to certain risk groups. These include patients:

• in whom significant improvement in glycemic control has occurred,
• in whom hypoglycemia develops gradually,
• elderly patients,
• those who have switched from animal-source insulin to human insulin,
• with autonomic (vegetative) neuropathy,
• with long-standing diabetes mellitus,
• with psychiatric disorders,
• receiving concomitant therapy with certain other medicinal products (see section "Interaction with other medicinal products and other forms of interaction").

In such situations, severe hypoglycemia (possibly with loss of consciousness) may occur before the patient realizes that their blood glucose level has dropped.

Since subcutaneously administered insulin glargine acts over a prolonged period, normalization of the glycemic state may require more time.

If a patient has normal or low glycated hemoglobin levels, this may indicate the occurrence of undiagnosed (especially nocturnal) episodes of hypoglycemia.

Strict adherence to the prescribed dose, dietary regimen, proper insulin administration, and patient awareness of hypoglycemia symptoms are crucial for reducing the risk of hypoglycemia. Several factors increase susceptibility to hypoglycemia and require careful monitoring of the patient's condition, and sometimes dose adjustment. These include:

• change in insulin injection site,
• increased insulin sensitivity (e.g., after removal of stress factors),
• unusual, excessive, or prolonged physical exertion,
• concomitant illness (e.g., vomiting, diarrhea),
• inadequate nutrition,
• missed meals,
• alcohol consumption,
• certain endocrine disorders (thyroid dysfunction, hypopituitarism, or adrenal insufficiency) in the decompensated stage,
• concomitant use of certain other medicinal products.

Concomitant diseases

The presence of concomitant illness requires intensified monitoring of metabolic parameters. In many cases, urine testing for ketones is indicated, and frequent insulin dose adjustments may be necessary. Insulin requirements often increase. Patients with type 1 diabetes mellitus must continue to consume at least a small amount of carbohydrates regularly, even if they are able to eat only minimal amounts or cannot eat at all, or if they experience vomiting. They should never completely discontinue insulin therapy.

Insulin antibodies

Administration of insulin preparations may lead to the formation of insulin antibodies. In rare cases, the presence of insulin antibodies may necessitate dose adjustment to prevent hypoglycemia or hyperglycemia (see section "Pharmacological properties").

Use of the pen device

Before using the SoloStar® pen device, the instructions for use should be carefully read. SoloStar® should be used in accordance with the recommendations provided in these instructions (see section "Instructions for use of the Lantus® SoloStar® pen device").

Accidental administration of another product

Reports have been received regarding accidental administration of insulin products when other insulins, particularly short-acting insulins, were inadvertently injected instead of insulin glargine. The label on the insulin vial or pen should be checked before each injection to avoid accidental administration of insulins other than insulin glargine.

Combination of Lantus® SoloStar® with pioglitazone

Cases of heart failure have been reported when pioglitazone was used in combination with insulin, particularly in patients at risk of developing heart failure. This should be considered when evaluating the possibility of treatment with a combination of pioglitazone and Lantus® SoloStar®. When using this combination, patients should be medically monitored for possible signs and symptoms of heart failure, weight gain, and edema. If any worsening of cardiac symptoms occurs, pioglitazone should be discontinued.

Excipients

This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e., it is essentially "sodium-free."

Use during pregnancy or breastfeeding.

Pregnancy. There are no clinical data from controlled clinical trials on the use of insulin glargine during pregnancy. However, extensive post-marketing surveillance data from over 1000 pregnancies indicate that insulin glargine does not adversely affect pregnancy outcomes and does not cause fetal or neonatal malformations or toxicity. Animal studies have not shown signs of reproductive toxicity. Lantus® SoloStar® may be prescribed during pregnancy if needed.

It is very important for patients with pre-existing diabetes and those with gestational diabetes to maintain adequate metabolic control throughout pregnancy to prevent adverse clinical outcomes associated with hyperglycemia. Insulin requirements may decrease during the first trimester and increase during the second and third trimesters. Insulin requirements drop rapidly immediately after delivery (increased risk of hypoglycemia). Therefore, careful monitoring of blood glucose levels is essential.

Breastfeeding. It is currently unknown whether insulin glargine is excreted in human milk. Metabolic effects in the newborn/infant due to insulin glargine passage into breast milk are not expected, as insulin glargine is a peptide that is degraded into amino acids in the human gastrointestinal tract. However, women who are breastfeeding may require adjustments in insulin dosage and diet.

Fertility.

Animal studies have not shown a direct harmful effect on fertility.

Ability to affect reaction speed when driving or operating machinery.

A patient's ability to concentrate and reaction speed may be impaired due to hypoglycemia or hyperglycemia, or, for example, due to visual disturbances. This may be dangerous in situations where these abilities are particularly important (such as when driving vehicles or operating machinery).

Patients should be advised to take necessary precautions to avoid hypoglycemia while driving. This is especially important for patients in whom early symptoms of hypoglycemia are weak or absent, as well as for those in whom hypoglycemia occurs frequently. Careful consideration should be given to whether driving or operating machinery is appropriate under such conditions.

Method of Administration and Dosage

Dosage

Lantus® SoloStar® contains insulin glargine – a long-acting insulin analogue. The medication is administered once daily at any time of day, but always at the same time.

The dosage regimen for Lantus® SoloStar® (dose and timing of administration) should be individually adjusted. In patients with type 2 diabetes mellitus, Lantus® SoloStar® may also be used concomitantly with oral antidiabetic medicinal products. The potency of this medicinal product is expressed in units. These units apply exclusively to Lantus® SoloStar® and differ from IU or units used to express the potency of other insulin analogues (see section "Pharmacological Properties").

Children and adolescents

The safety and efficacy of insulin Lantus® SoloStar® have been established in adolescents and children aged 2 years and older (see section "Pharmacological Properties"). Use of Lantus® SoloStar® in children under 2 years of age has not been studied.

Elderly patients (over 65 years of age)

In elderly patients, progressive age-related decline in renal function may lead to a continuous decrease in insulin requirements.

Renal impairment

In patients with renal impairment, insulin requirements may be reduced due to decreased insulin metabolism.

Hepatic impairment

In patients with hepatic impairment, insulin requirements may be reduced due to decreased capacity for gluconeogenesis and slowed insulin metabolism.

Switching from other insulins to Lantus® SoloStar®

When switching from intermediate-acting or long-acting insulin regimens to a treatment regimen with Lantus® SoloStar®, a change in basal insulin dose may be required, as well as adjustments to concomitant antidiabetic therapy (doses and timing of administration of supplementary regular insulin or fast-acting insulin analogues, or doses of oral antidiabetic medicinal products).

Switching from twice-daily NPH insulin (neutral protamine Hagedorn) to Lantus® SoloStar®

To reduce the risk of nocturnal or early morning hypoglycemia, patients switching from a twice-daily NPH insulin regimen to once-daily Lantus® SoloStar® should reduce their basal insulin dose by 20–30% during the first weeks of treatment.

Switching from insulin glargine 300 IU/mL to Lantus® SoloStar®

Lantus® SoloStar® and Toujeo SoloStar® (insulin glargine 300 IU/mL) are not bioequivalent and cannot be used interchangeably without dose adjustment. To reduce the risk of hypoglycemia, patients switching from once-daily insulin glargine 300 IU/mL to once-daily Lantus® SoloStar® should reduce their basal insulin dose by approximately 20%.

During this dose reduction period, the reduction should be at least partially compensated by increasing the dose of mealtime insulin. After completion of this period, the dosage regimen should be individually adjusted.

Careful monitoring of metabolic parameters is recommended during the transition period and for the first weeks thereafter.

Improvement in metabolic control and the associated increase in insulin sensitivity may require additional dose adjustments. Dose adjustments may also be necessary, for example, due to changes in body weight or lifestyle, changes in the time of day insulin is administered, or the occurrence of other factors predisposing to hypoglycemia or hyperglycemia (see section "Special Warnings and Precautions for Use").

In patients receiving high insulin doses due to the presence of antibodies to human insulin, switching to Lantus® SoloStar® may result in improved response to insulin administration.

Administration method

Lantus® SoloStar® should be administered subcutaneously by injection into the abdominal wall, thigh, shoulder, deltoid, or gluteal region. Injection sites should always be rotated within the same region to reduce the risk of lipodystrophy and cutaneous amyloidosis (see sections "Special Warnings and Precautions for Use" and "Undesirable Effects").

Lantus® SoloStar® must not be administered intravenously. The prolonged action of Lantus® SoloStar® is due to its subcutaneous administration into subcutaneous adipose tissue. Intravenous administration of a usual subcutaneous dose may lead to severe hypoglycemia.

There is no clinically significant difference in plasma insulin or glucose levels after administration of Lantus® SoloStar® into the abdominal area, deltoid region, or thigh. The injection site should be changed with each injection within the recommended body area.

Lantus® SoloStar® must not be mixed with any other insulin or diluted. Mixing or dilution may alter the time-action profile of the product. In addition, mixing with other insulins may lead to precipitation.

Before using the SoloStar® pen, carefully read the section "Instructions for Use of the Lantus® SoloStar® Pen".

Before first use, the pen should be allowed to reach room temperature for 1–2 hours. Inspect the cartridge before use. It may only be used if the solution is clear, colorless, free of visible particles, and has a watery consistency. Since Lantus® SoloStar® is a solution, it does not require resuspension before use.

Used pens must not be reused and should be properly disposed of.

To prevent infection, each pen must be used by only one person.

Before each injection, check the label on the insulin to avoid accidental injection of an insulin other than insulin glargine (see section "Special Warnings and Precautions for Use").

INSTRUCTIONS

for Use of the Lantus® SoloStar® Pen

Carefully and completely read these instructions before first use of the pen. Re-read the instructions as needed before subsequent use. Keep these instructions as they may need to be consulted in the future.

Before starting to use the SoloStar® pen, carefully read these instructions. If you are unable to fully follow all instructions independently, use the SoloStar® pen only with the help of a person who can follow the instructions. Hold the pen as shown in these instructions. To ensure correct dose setting, hold the pen horizontally with the needle on the left and the dose selector on the right, as shown in the illustrations below.

Doses from 1 to 80 units can be set in increments of 1 unit. Each pen contains multiple doses.

Schematic illustration of the Lantus® SoloStar® pen

Pen components

Important information on the use of the Lantus® SoloStar® pen

• Use a new needle for each injection, compatible only with the Lantus® SoloStar® pen.
• Perform a safety test before each injection.
• The pen is intended for personal use only and must not be shared with others.
• If another person administers the injection, they must take special safety precautions to avoid needle-related accidents and transmission of infection.
• Do not use the Lantus® SoloStar® pen if it is damaged or if you have any doubts about its proper functioning.
• Always keep a spare Lantus® SoloStar® pen in case of loss or damage.

Stage 1. Insulin check.

1. Carefully read the label on your pen to ensure you are using the correct insulin. The Lantus® SoloStar® pen is gray with a purple injection button.
2. Remove the pen cap.
3. Check the appearance of the insulin. Lantus® is a clear insulin. Do not use the Lantus® SoloStar® pen if the insulin is cloudy, discolored, or contains foreign particles.

Stage 2. Attaching the needle.

Always use a new sterile needle for each injection. This helps prevent contamination and possible needle clogging.

A. Remove the protective tab from the needle package.

B. Align the needle with the pen and attach it straight (screw on or push on, depending on needle type).

• If the needle is not aligned during attachment, it may damage the rubber seal, leading to leakage or needle breakage.

Stage 3. Safety test.

Always perform a safety test before each injection to ensure accurate dosing by:

• confirming the pen and needle are functioning properly;
• removing air bubbles.
  1. Set a dose of 2 units by turning the dose selector.
  2. Remove the outer needle cap and keep it for later use to cover the used needle after injection. Remove and discard the inner needle cap.
  3. Hold the pen with the needle pointing upward.
  4. Gently tap the insulin reservoir with your fingertips to bring air bubbles to the top near the needle.
  5. Press the injection button fully. Check if insulin appears at the needle tip.

Repeat the safety test several times until insulin appears.

• If no insulin appears, check for air bubbles and repeat the safety test up to two more times.
• If no insulin appears, this may indicate needle blockage. Replace the needle and repeat the test.
• If no insulin appears after needle replacement, this may indicate a damaged pen. Do not use it.

Stage 4. Selecting the dose.

Doses can be set in 1-unit increments (from a minimum of 1 unit to a maximum of 80 units). If a dose greater than 80 units is required, administer two or more injections.

1. Ensure the dose window shows "0" after completing the safety test.
2. Select the required dose (in the example below, 30 units are selected). If you set a dose higher than needed, turn the dose selector back to the correct dose.
   • Do not press the injection button while turning the selector, or insulin will leak.
   • You cannot turn the dose selector beyond the amount remaining in the pen. Do not force it. Either inject the remaining insulin glargine and supplement your required dose with a new pen, or use a new Lantus® SoloStar® to administer the full dose.

Stage 5. Injection technique.

A. Follow the injection technique as instructed by your healthcare provider.

B. Insert the needle into the skin.

C. Administer the dose by pressing the injection button fully. After injection, the dose window should display "0".

D. Keep the injection button pressed. Slowly count to 10 before removing the needle from the skin. This ensures complete dose delivery.

Stage 6. Removing and disposing of the needle.

Always remove the needle after each injection and store the pen without an attached needle. This helps prevent:

• contamination and/or infection;
• air entering the insulin reservoir and insulin leakage, which may lead to incorrect dosing.
  1. Replace the outer needle cap onto the needle and use it to unscrew the needle from the pen. To reduce the risk of needle-stick injuries, never replace the inner needle cap.
• If another person administers the injection, they must take special precautions when removing and disposing of the needle (e.g., one-handed capping technique) to reduce the risk of needle-stick injuries and transmission of infectious diseases.
  1. Dispose of the needle carefully (in accordance with local regulations).
  2. Always cap the pen and store it until the next injection.

Storage instructions.

Carefully follow the storage instructions for the Lantus® SoloStar® pen.

If the Lantus® SoloStar® pen has been stored in the refrigerator, remove it 1–2 hours before injection to allow it to warm to room temperature. Injecting cold insulin may be more painful.

Used Lantus® SoloStar® pens must be destroyed according to local regulations.

Handling.

Protect the Lantus® SoloStar® pen from dust and dirt.

Clean the outer surface of the pen with a damp cloth.

Do not immerse the pen in liquid, do not rinse or lubricate it, as this may damage it.

The Lantus® SoloStar® pen is designed for accurate and safe operation.

Use it with care. Avoid situations that may damage the pen. If you suspect the Lantus® SoloStar® pen is damaged, use a new one.

Children.

The safety and efficacy of Lantus® SoloStar® have been established in adolescents and children aged 2 years and older.

Overdose.

Symptoms

Insulin overdose may lead to severe, sometimes prolonged hypoglycemia, which may be life-threatening.

Treatment

Mild episodes of hypoglycemia can usually be corrected by oral administration of carbohydrates. Dose adjustment of the medicinal product and changes in diet or physical activity may also be required.

More severe episodes of hypoglycemia accompanied by coma, seizures, or neurological impairment require intramuscular/subcutaneous administration of glucagon or intravenous administration of concentrated glucose solution. Since hypoglycemia may recur even after apparent clinical improvement, prolonged carbohydrate intake and patient monitoring are necessary.

Adverse Reactions

General overview of the drug's safety profile

Hypoglycemia (very common) is generally the most frequently observed adverse reaction during insulin therapy. It occurs when the administered insulin dose greatly exceeds the individual's insulin requirement (see section "Special Warnings and Precautions for Use").

Tabulated list of adverse reactions

Adverse reactions associated with the use of the drug observed during clinical studies are listed below by system organ classes in decreasing order of frequency: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000); frequency not known (cannot be estimated from the available data).

Within each of these groups, adverse reactions are listed in decreasing order of severity.

Description of individual adverse reactions

Metabolic and nutritional disorders

Severe episodes of hypoglycaemia, especially if they occur repeatedly, may lead to damage of the nervous system. Prolonged or severe hypoglycaemia may be life-threatening.

In many patients, symptoms indicating inadequate glucose supply to brain tissue (neuroglycopaenia) are preceded by signs of adrenergic counter-regulation. Generally, the greater and faster the decline in blood glucose levels, the more pronounced the adrenergic counter-regulation and the more intense the characteristic symptoms (see section "Special precautions for use").

Immune system disorders

Immediate-type hypersensitivity reactions to insulin are rare. Such reactions to insulin (including insulin glargine) or excipients may manifest as, for example, generalized skin reactions, angioedema, bronchospasm, hypotension, and shock, which may be life-threatening.

Administration of insulin preparations may lead to formation of insulin antibodies. In clinical trials, among patient groups receiving treatment with NPH insulin and insulin glargine, formation of antibodies cross-reacting with human insulin was observed with equal frequency. In isolated cases, the presence of insulin antibodies may necessitate dose adjustment to prevent the occurrence of hypoglycaemia or hyperglycaemia.

Eye disorders

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

The risk of progression of diabetic retinopathy is reduced when sustained normalization of blood glucose levels is achieved. However, intensification of insulin therapy with sudden improvement in glycaemic control may be accompanied by transient worsening of diabetic retinopathy. In patients with proliferative retinopathy, especially in those who have not undergone photocoagulation, episodes of severe hypoglycaemia may lead to transient loss of vision.

Skin and subcutaneous tissue disorders

As with other insulin preparations, lipodystrophy and cutaneous amyloidosis may occur at the injection site, resulting in reduced insulin absorption rate at the injection site. Regular rotation of injection sites within a single injection area may help reduce or prevent these phenomena (see section "Special precautions for use").

General disorders and administration site reactions

Reactions at the injection site include erythema, pain, pruritus, urticaria, swelling, or inflammation. Most mild reactions to insulin occurring at the injection site usually resolve within a period of several days to several weeks.

Insulin may rarely cause sodium retention and oedema, particularly when improved glycaemic control is achieved after intensification of insulin therapy in patients with previously inadequate glycaemic control.

Children and adolescents

Overall, the safety profile of the drug in children and adolescents (up to 18 years of age) is not different from its safety profile in adult patients.

In reports of adverse reactions obtained during post-marketing surveillance, relatively more frequent occurrence of injection site reactions (pain at injection site, reaction at injection site) and skin reactions (rash, urticaria) has been reported in children and adolescents (≤18 years) compared to adults. Clinical data on the safety of the drug use in children under 2 years of age are currently lacking.

Reporting of suspected adverse reactions

Reporting of suspected adverse reactions after marketing authorization is an important procedure. It allows continuous monitoring of the benefit-risk ratio of the medicinal product. Healthcare professionals are requested to report all suspected adverse reactions via national reporting systems.

Shelf life. 3 years.

Shelf life after first use of the pen device

This medicinal product should be stored for a maximum of 4 weeks at a temperature not exceeding +30 °C, protected from direct heat and direct light.

Pen devices in use must not be stored in the refrigerator.

After each injection, the cap should be replaced on the pen device to protect it from light.

Storage conditions.

Keep out of the reach and sight of children.

Pen devices not in use

Store at +2 °C – +8 °C. Do not freeze!

Avoid contact with the freezer compartment or cold accumulators.

Store the pen device in its outer cardboard packaging to protect it from light.

Pen devices in use

Storage conditions, see section "Shelf life".

Incompatibilities.

This medicinal product must not be mixed with other medicinal products.

Packaging.

No. 5: 3 mL in a cartridge contained in a disposable pen device (without injection needles); 5 pen devices in a cardboard box.

Prescription category. Prescription only.

Manufacturer.

Sanofi-Aventis Deutschland GmbH / Sanofi-Aventis Deutschland GmbH.

Manufacturer's address and location of its operations.

Bruningstrasse 50, Industriepark Hoechst, 65926 Frankfurt am Main, Germany.

Industriepark Hoechst-Bruningstrasse 50, Frankfurt am Main, 65926, Germany