This information is intended for use by health professionals

Lantus 100 units/ml solution for injection in a cartridge

Each ml contains 100 units insulin glargine* (equivalent to three.64 mg).

Each cartridge contains 3 ml of solution for injection, equivalent to 300 units.

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

For the total list of excipients, encounter section 6.one.

Solution for injection.

Articulate colourless solution.

Treatment of diabetes mellitus in adults, adolescents and children anile ii years and higher up.

Posology

Lantus contains insulin glargine, an insulin analogue, and has a prolonged duration of action.

Lantus should be administered one time daily at any time simply at the same fourth dimension each day.

The dose regimen (dose and timing) should exist individually adjusted. In patients with type ii diabetes mellitus, Lantus tin also be given together with orally active antidiabetic medicinal products.

The authorization of this medicinal product is stated in units. These units are sectional to Lantus and are not the same every bit IU or the units used to express the potency of other insulin analogues (meet section five.1).

Special population

Elderly population (≥65 years old)

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 to reduced insulin metabolism.

Hepatic impairment

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

Paediatric population

• Adolescents and children aged ii years and older patients

Rubber and efficacy of Lantus take been established in adolescents and children anile 2 years and older (see department v.one). The dose regimen (dose and timing) should be individually adjusted.

• Children below 2 years of age

The safety and efficacy of Lantus accept not been established. No data are available.

Switch from other insulins to Lantus

When switching from a treatment regimen with an intermediate or long-interim insulin to a regimen with Lantus, a alter of the dose of the basal insulin may exist required and the concomitant antidiabetic handling may need to exist adjusted (dose and timing of additional regular insulins or fast-acting insulin analogues or the dose of oral antidiabetic medicinal products).

Switch from twice daily NPH insulin to Lantus

To reduce the take chances of nocturnal and early morn hypoglycaemia, patients who are irresolute their basal insulin regimen from a twice daily NPH insulin to a in one case daily regimen with Lantus should reduce their daily dose of basal insulin by 20-xxx% during the commencement weeks of treatment.

Switch from insulin glargine 300 units/ml to Lantus

Lantus and Toujeo (insulin glargine 300 units/ml) are not bioequivalent and are not directly interchangeable. To reduce the take a chance of hypoglycemia, patients who are changing their basal insulin regimen from an insulin regimen with one time daily insulin glargine 300 units/ml to a once daily regimen with Lantus should reduce their dose by approximately twenty%.

During the first weeks the reduction should, at least partially, be compensated past an increment in mealtime insulin, after this period the regimen should exist adjusted individually.

Close metabolic monitoring is recommended during the switch and in the initial weeks thereafter.

With improved metabolic control and resulting increase in insulin sensitivity a further adjustment in dose regimen may become necessary. Dose adjustment may also exist required, for example, if the patient'due south weight or life-style changes, change of timing of insulin dose or other circumstances arise that increase susceptibility to hypo- or hyperglycaemia (see section iv.iv).

Patients with high insulin doses considering of antibodies to human insulin may feel an improved insulin response with Lantus.

Method of assistants

Lantus is administered subcutaneously.

Lantus should not be administered intravenously. The prolonged elapsing of action of Lantus is dependent on its injection into subcutaneous tissue. Intravenous administration of the usual subcutaneous dose could result in severe hypoglycaemia.

There are no clinically relevant differences in serum insulin or glucose levels after abdominal, deltoid or thigh administration of Lantus. Injection sites must be rotated within a given injection area from 1 injection to the next in lodge to reduce the take chances of lipodystrophy and cutaneous amyloidosis (run into department iv.four and 4.8).

Lantus must not exist mixed with any other insulin or diluted. Mixing or diluting can alter its fourth dimension/activeness profile and mixing tin cause precipitation.

Lantus 100 units/ml in cartridges is only suitable for subcutaneous injections from a reusable pen. If administration past syringe is necessary, a vial should be used (see section four.4).

For farther details on handling, see section 6.6.

Hypersensitivity to the active substance or to any of the excipients listed in department vi.i.

Traceability

In lodge to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.

Lantus is not the insulin of choice for the treatment of diabetic ketoacidosis. Instead, regular insulin administered intravenously is recommended in such cases.

In instance of insufficient glucose control or a tendency to hyper- or hypoglycaemic episodes, the patient'southward adherence to the prescribed treatment regimen, injection sites and proper injection technique and all other relevant factors must exist reviewed before dose adjustment is considered.

Transferring a patient to another blazon or make of insulin should be done nether strict medical supervision. Changes in strength, brand (manufacturer), type (regular, NPH, lente, long-acting, etc.), origin (creature, human, human insulin analogue) and/or method of industry may outcome in the demand for a alter in dose.

Patients must be instructed to perform continuous rotation of the injection site to reduce the risk of developing lipodystrophy and cutaneous amyloidosis. There is a potential take chances of delayed insulin absorption and worsened glycaemic control following insulin injections at sites with these reactions. A sudden change in the injection site to an unaffected surface area has been reported to upshot in hypoglycaemia. Blood glucose monitoring is recommended after the change in the injection site, and dose adjustment of antidiabetic medications may exist considered.

Hypoglycaemia

The time of occurrence of hypoglycaemia depends on the activity contour of the insulins used and may, therefore, change when the treatment regimen is changed. Due to more sustained basal insulin supply with Lantus, less nocturnal simply more early on morning hypoglycaemia tin can be expected.

Item caution should be exercised, and intensified blood glucose monitoring is advisable in patients in whom hypoglycaemic episodes might exist of particular clinical relevance, such as in patients with significant stenoses of the coronary arteries or of the blood vessels supplying the encephalon (chance of cardiac or cerebral complications of hypoglycaemia) also as in patients with proliferative retinopathy, particularly if non treated with photocoagulation (risk of transient amaurosis following hypoglycaemia).

Patients should be aware of circumstances where warning symptoms of hypoglycaemia are diminished. The alarm symptoms of hypoglycaemia may exist inverse, be less pronounced or be absent in certain risk groups. These include patients:

- in whom glycaemic command is markedly improved,

- in whom hypoglycaemia develops gradually,

- who are elderly,

- afterward transfer from animate being insulin to human insulin,

- in whom an autonomic neuropathy is nowadays,

- with a long history of diabetes,

- suffering from a psychiatric illness,

- receiving concurrent treatment with certain other medicinal products (see department 4.5).

Such situations may result in severe hypoglycaemia (and maybe loss of consciousness) prior to the patient's sensation of hypoglycaemia.

The prolonged effect of subcutaneous insulin glargine may delay recovery from hypoglycaemia.

If normal or decreased values for glycated haemoglobin are noted, the possibility of recurrent, unrecognised (especially nocturnal) episodes of hypoglycaemia must be considered.

Adherence of the patient to the dose and dietary regimen, right insulin administration and awareness of hypoglycaemia symptoms are essential to reduce the run a risk of hypoglycaemia. Factors increasing the susceptibility to hypoglycaemia crave particularly close monitoring and may necessitate dose adjustment. These include:

- change in the injection area,

- improved insulin sensitivity (east.m., by removal of stress factors),

- unaccustomed, increased or prolonged physical activity,

- intercurrent illness (e.m. vomiting, diarrhoea),

- inadequate food intake,

- missed meals,

- alcohol consumption,

- certain uncompensated endocrine disorders, (e.g. in hypothyroidism and in anterior pituitary or adrenocortical insufficiency),

- concomitant treatment with sure other medicinal products (run across department 4.5).

Intercurrent illness

Intercurrent disease requires intensified metabolic monitoring. In many cases urine tests for ketones are indicated, and often it is necessary to adjust the insulin dose. The insulin requirement is oft increased. Patients with blazon 1 diabetes must continue to consume at to the lowest degree a small amount of carbohydrates on a regular ground, fifty-fifty if they are able to eat only little or no food, or are vomiting etc. and they must never omit insulin entirely.

Insulin antibodies

Insulin administration may cause insulin antibodies to grade. In rare cases, the presence of such insulin antibodies may necessitate adjustment of the insulin dose in order to correct a tendency to hyper- or hypoglycaemia (see section v.1).

Pens to exist used with Lantus 100 units/ml in cartridges

Lantus 100 units/ml in cartridges is merely suitable for subcutaneous injections from a reusable pen. If assistants by syringe is necessary, a vial should be used. The Lantus cartridges should simply exist used with the post-obit pens:

- JuniorSTAR which delivers Lantus in 0.5 unit dose increments

- ClikSTAR, Tactipen, Autopen 24, AllStar and AllStar PRO which all deliver Lantus in 1 unit dose increments.

These cartridges should not be used with whatsoever other reusable pen as the dosing accuracy has only been established with the listed pens.

Not all of these pens may be marketed in your country (see department 4.2 and vi.6)

Medication errors

Medication errors have been reported in which other insulins, particularly short-acting insulins, accept been accidentally administered instead of insulin glargine. Insulin label must e'er be checked before each injection to avoid medication errors betwixt insulin glargine and other insulins.

Combination of Lantus with pioglitazone

Cases of cardiac failure have been reported when pioglitazone was used in combination with insulin, especially in patients with run a risk factors for development of cardiac heart failure. This should exist kept in mind if treatment with the combination of pioglitazone and Lantus is considered. If the combination is used, patients should be observed for signs and symptoms of heart failure, weight gain and oedema. Pioglitazone should exist discontinued if any deterioration in cardiac symptoms occurs.

Excipients

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

A number of substances affect glucose metabolism and may require dose adjustment of insulin glargine.

Substances that may enhance the blood-glucose-lowering event and increment susceptibility to hypoglycaemia include oral antidiabetic medicinal products, angiotensin converting enzyme (ACE) inhibitors, disopyramide, fibrates, fluoxetine, monoamine oxidase (MAO) inhibitors, pentoxifylline, propoxyphene, salicylates and sulfonamide antibiotics.

Substances that may reduce the blood-glucose-lowering event include corticosteroids, danazol, diazoxide, diuretics, glucagon, isoniazid, oestrogens and progestogens, phenothiazine derivatives, somatropin, sympathomimetic medicinal products (e.yard. epinephrine [adrenaline], salbutamol, terbutaline), thyroid hormones, atypical antipsychotic medicinal products (eastward.one thousand. clozapine 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 equally beta-blockers, clonidine, guanethidine and reserpine, the signs of adrenergic counter-regulation may be reduced or absent.

Pregnancy

For insulin glargine no clinical data on exposed pregnancies from controlled clinical studies are available. A large amount of data on pregnant women (more than than 1000 pregnancy outcomes) point no specific adverse effects of insulin glargine on pregnancy and no specific malformative nor feto/neonatal toxicity of insulin glargine. Animate being information exercise non indicate reproductive toxicity.

The use of Lantus may be considered during pregnancy, if clinically needed.

It is essential for patients with pre-existing or gestational diabetes to maintain skilful metabolic control throughout pregnancy to prevent adverse outcomes associated with hyperglycemia. Insulin requirements may decrease during the first trimester and generally increase during the 2nd and tertiary trimesters. Immediately after delivery, insulin requirements turn down rapidly (increased risk of hypoglycaemia). Careful monitoring of glucose control is essential.

Chest-feeding

It is unknown whether insulin glargine is excreted in human milk. No metabolic effects of ingested insulin glargine on the breast-fed newborn/infant are anticipated since insulin glargine as a peptide is digested into aminoacids in the man gastrointestinal tract. Breast-feeding women may require adjustments in insulin dose and diet.

Fertility

Brute studies do not bespeak direct harmful effects with respect to fertility.

The patient'southward ability to concentrate and react may be dumb equally a result of hypoglycaemia or hyperglycaemia or, for case, as a result of visual harm. This may constitute a risk in situations where these abilities are of special importance (e.g. driving a car or using machines).

Patients should be advised to take precautions to avert hypoglycaemia whilst driving. This is particularly of import in those who have reduced or absent awareness of the warning symptoms of hypoglycaemia or have frequent episodes of hypoglycaemia. It should be considered whether it is appropriate to drive or use machines in these circumstances.

Summary of the safety profile

Hypoglycaemia (very mutual), in general the nearly frequent adverse reaction of insulin therapy, may occur if the insulin dose is likewise high in relation to the insulin requirement (come across section 4.iv).

Tabulated listing of agin reactions

The following related adverse reactions from clinical investigations are listed below by arrangement organ course and in order of decreasing incidence (very common: ≥1/ten; mutual: ≥1/100 to <ane/10; uncommon: ≥1/1,000 to <1/100; rare: ≥i/x,000 to <1/1,000; very rare: <1/x,000; not known: cannot exist estimated from the available data).

Within each frequency grouping, agin reactions are presented in order of decreasing seriousness.

MedDRA system organ classes

Very common

Common

Uncommon

Rare

Very rare

Non known

Immune organisation disorders

Allergic reactions

Metabolism and nutrition disorders

Hypoglycaemia

Nervous system disorders

Dysgeusia

Optics disorders

Visual impairment

Retinopathy

Skin and subcutaneous tissue disorders

Lipohypertrophy

Lipoatrophy

Cutaneous amyloidosis

Musculoskeletal and connective tissue disorders

Myalgia

Full general disorders and assistants site conditions

Injection site reactions

Oedema

Description of selected adverse reactions

Metabolism and diet disorders

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 past signs of adrenergic counter-regulation. Generally, the greater and more rapid the reject in blood glucose, the more marked is the miracle of counter-regulation and its symptoms (see section iv.4).

Immune organisation disorders

Firsthand-type allergic reactions to insulin are rare. Such reactions to insulin (including insulin glargine) or the excipients may, for case, be associated with generalised skin reactions, angio-oedema, bronchospasm, hypotension and stupor, and may exist life-threatening.

Eyes disorders

A marked alter in glycaemic control may cause temporary visual impairment, due to temporary alteration in the turgidity and refractive index of the lens.

Long-term improved glycaemic control decreases the adventure of progression of diabetic retinopathy. However, intensification of insulin therapy with abrupt comeback in glycaemic command may be associated with 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

Lipodystrophy and cutaneous amyloidosis may occur at the injection site and delay local insulin assimilation. Continuous rotation of the injection site inside the given injection area may help to reduce or prevent these reactions (see department four.4).

General disorders and assistants site weather condition

Injection site reactions include redness, pain, itching, hives, swelling, or inflammation. Most minor reactions to insulins at the injection site normally resolve in a few days to a few weeks.

Rarely, insulin may cause sodium retention and oedema specially if previously poor metabolic control is improved by intensified insulin therapy.

Paediatric population

In full general, the rubber contour for children and adolescents (≤eighteen years of age) is similar to the safety profile for adults.

The adverse reaction reports received from post marketing surveillance included relatively more frequent injection site reactions (injection site hurting, injection site reaction) and skin reactions (rash, urticaria) in children and adolescents (≤18 years of historic period) than in adults.

Clinical written report safety information are not bachelor for children under two years.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions later on authorisation of the medicinal production is important. Information technology allows continued monitoring of the benefit/hazard balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via Yellow Carte Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Carte in the Google Play or Apple App Shop.

Symptoms

Insulin overdose may lead to severe and sometimes long-term and life-threatening hypoglycaemia.

Management

Mild episodes of hypoglycaemia can usually be treated with oral carbohydrates. Adjustments in dose of the medicinal product, repast patterns, or concrete activity may be needed.

More severe episodes with coma, seizure, or neurologic harm may be treated with intramuscular/subcutaneous glucagon or concentrated intravenous glucose. Sustained sugar intake and observation may be necessary because hypoglycaemia may recur after apparent clinical recovery.

Pharmacotherapeutic group: Drugs used in diabetes, insulins and analogues for injection, long-interim. ATC Lawmaking: A10AE04.

Mechanism of activity

Insulin glargine is a human insulin analogue designed to take a low solubility at neutral pH. It is completely soluble at the acidic pH of the Lantus injection solution (pH four). After injection into the subcutaneous tissue, the acidic solution is neutralised leading to formation of micro-precipitates from which small amounts of insulin glargine are continuously released, providing a smooth, peakless, predictable concentration/fourth dimension profile with a prolonged duration of activity.

Insulin glargine is metabolised into 2 active metabolites M1 and M2 (encounter section v.2).

Insulin receptor binding: In vitro studies point that the affinity of insulin glargine and its metabolites M1 and M2 for the homo insulin receptor is similar to the one of human insulin.

IGF-1 receptor bounden: The affinity of insulin glargine for the homo IGF-1 receptor is approximately 5 to viii-fold greater than that of human insulin (but approximately 70 to 80-fold lower than the ane of IGF-1), whereas M1 and M2 bind the IGF-1 receptor with slightly lower affinity compared to human insulin.

The total therapeutic insulin concentration (insulin glargine and its metabolites) establish in type ane diabetic patients was markedly lower than what would exist required for a halfmaximal occupation of the IGF-one receptor and the subsequent activation of the mitogenic-proliferative pathway initiated by the IGF-1 receptor. Physiological concentrations of endogenous IGF-1 may activate the mitogenic-proliferative pathway; however, the therapeutic concentrations establish in insulin therapy, including in Lantus therapy, are considerably lower than the pharmacological concentrations required to activate the IGF-1 pathway.

The primary action of insulin, including insulin glargine, is regulation of glucose metabolism. Insulin and its analogues lower blood glucose levels by stimulating peripheral glucose uptake, particularly by skeletal muscle and fat, and by inhibiting hepatic glucose product. Insulin inhibits lipolysis in the adipocyte, inhibits proteolysis and enhances poly peptide synthesis.

In clinical pharmacology studies, intravenous insulin glargine and man insulin have been shown to exist equipotent when given at the same doses. As with all insulins, the fourth dimension form of action of insulin glargine may exist afflicted past physical activity and other variables.

In euglycaemic clamp studies in healthy subjects or in patients with blazon i diabetes, the onset of action of subcutaneous insulin glargine was slower than with homo NPH insulin, its effect profile was smooth and peakless, and the elapsing of its effect was prolonged.

The following graph shows the results from a study in patients:

Activity profile in patients with type 1 diabetes

*adamant every bit amount of glucose infused to maintain constant plasma glucose levels (hourly mean values)

The longer duration of action of subcutaneous insulin glargine is directly related to its slower rate of absorption and supports once daily administration. The time class of activity of insulin and insulin analogues such as insulin glargine may vary considerably in different individuals or inside the same individual.

In a clinical study, symptoms of hypoglycaemia or counter-regulatory hormone responses were similar later on intravenous insulin glargine and human insulin both in healthy volunteers and patients with blazon 1 diabetes.

In clinical studies, antibodies that cross-react with human insulin and insulin glargine were observed with the same frequency in both NPH-insulin and insulin glargine treatment groups.

Furnishings of insulin glargine (once daily) on diabetic retinopathy were evaluated in an open-characterization v year NPH-controlled study (NPH given bid) in 1024 type 2 diabetic patients in which progression of retinopathy by 3 or more than steps on the Early on Handling Diabetic Retinopathy Report (ETDRS) scale was investigated by fundus photography. No significant difference was seen in the progression of diabetic retinopathy when insulin glargine was compared to NPH insulin.

The ORIGIN (Outcome Reduction with Initial Glargine INtervention) written report was a multicenter, randomised, 2x2 factorial design report conducted in 12,537 participants at loftier cardiovascular (CV) hazard with impaired fasting glucose (IFG) or impaired glucose tolerance (IGT) (12% of participants) or blazon 2 diabetes mellitus treated with ≤1 antidiabetic oral amanuensis (88% of participants). Participants were randomised (1:one) to receive insulin glargine (n=6264), titrated to reach FPG ≤95 mg/dl (v.3 mM), or standard care (n=6273).

The first co-primary efficacy effect was the time to the showtime occurrence of CV death, nonfatal myocardial infarction (MI), or nonfatal stroke, and the 2d co-main efficacy effect was the time to the first occurrence of any of the showtime co-primary events, or revascularisation process (coronary, carotid, or peripheral), or hospitalisation for centre failure.

Secondary endpoints included all-cause mortality and a composite microvascular consequence.

Insulin glargine did non alter the relative take chances for CV affliction and CV mortality when compared to standard of care. At that place were no differences between insulin glargine and standard care for the ii co-primary outcomes; for any component endpoint comprising these outcomes; for all-crusade mortality; or for the composite microvascular result.

Mean dose of insulin glargine by study cease was 0.42 U/kg. At baseline, participants had a median HbA1c value of 6.4% and median on-treatment HbA1c values ranged from 5.9 to 6.iv% in the insulin glargine group, and half dozen.2% to 6.half-dozen% in the standard care group throughout the duration of follow-upwardly.

The rates of severe hypoglycaemia (affected participants per 100 participant years of exposure) were 1.05 for insulin glargine and 0.30 for standard care group and the rates of confirmed non-astringent hypoglycaemia were 7.71 for insulin glargine and 2.44 for standard care group. Over the course of this 6-year study, 42% of the insulin glargine grouping did not experience any hypoglycaemia.

At the last on-treatment visit, there was a mean increase in body weight from baseline of 1.iv kg in the insulin glargine group and a mean decrease of 0.eight kg in the standard care group.

Paediatric population

In a randomised, controlled clinical study, paediatric patients (historic period range half-dozen to xv years) with type 1 diabetes (n=349) were treated for 28 weeks with a basal-bolus insulin regimen where regular human insulin was used before each meal. Insulin glargine was administered once daily at bedtime and NPH human insulin was administered once or twice daily. Similar effects on glycohemoglobin and the incidence of symptomatic hypoglycemia were observed in both treatment groups, however fasting plasma glucose decreased more than from baseline in the insulin glargine grouping than in the NPH grouping. There was less severe hypoglycaemia in the insulin glargine group equally well. One hundred forty three of the patients treated with insulin glargine in this study continued handling with insulin glargine in an uncontrolled extension study with mean duration of follow-up of 2 years. No new safety signals were seen during this extended handling with insulin glargine.

A crossover study comparing insulin glargine plus lispro insulin to NPH plus regular human being insulin (each treatment administered for 16 weeks in random social club) in 26 boyish type i diabetic patients aged 12 to eighteen years was besides performed. Every bit in the paediatric written report described higher up, fasting plasma glucose reduction from baseline was greater in the insulin glargine grouping than in the NPH group. HbA1c changes from baseline were like between treatment groups; notwithstanding blood glucose values recorded overnight were significantly higher in the insulin glargine/ lispro group than the NPH/regular group, with a mean nadir of 5.4 mM versus 4.1 mM. Correspondingly, the incidences of nocturnal hypoglycaemia were 32% in the insulin glargine / lispro group versus 52% in the NPH / regular group.

A 24-calendar week parallel group study was conducted in 125 children with blazon ane diabetes mellitus aged 2 to half dozen years, comparison insulin glargine given one time daily in the forenoon to NPH insulin given in one case or twice daily every bit basal insulin. Both groups received bolus insulin earlier meals.

The primary aim of demonstrating non-inferiority of insulin glargine to NPH in all hypoglycaemia was not met and at that place was a tendency to an increase of hypoglycemic events with insulin glargine [insulin glargine: NPH rate ratio (95% CI) = ane.xviii (0.97-1.44)].

Glycohaemoglobin and glucose variabilities were comparable in both treatment groups. No new safety signals were observed in this report.

In healthy subjects and diabetic patients, insulin serum concentrations indicated a slower and much more prolonged assimilation and showed a lack of a peak afterwards subcutaneous injection of insulin glargine in comparison to human NPH insulin. Concentrations were thus consistent with the fourth dimension profile of the pharmacodynamic activity of insulin glargine. The graph higher up shows the activeness profiles over time of insulin glargine and NPH insulin.

Insulin glargine injected in one case daily will attain steady state levels in 2-4 days after the first dose.

When given intravenously the elimination one-half-life of insulin glargine and homo insulin were comparable.

Subsequently subcutaneous injection of Lantus in diabetic patients, insulin glargine is quickly metabolized at the carboxyl terminus of the Beta chain with formation of 2 active metabolites M1 (21A-Gly-insulin) and M2 (21A-Gly-des-30B-Thr-insulin). In plasma, the principal circulating compound is the metabolite M1. The exposure to M1 increases with the administered dose of Lantus. The pharmacokinetic and pharmacodynamic findings betoken that the effect of the subcutaneous injection with Lantus is principally based on exposure to M1. Insulin glargine and the metabolite M2 were not detectable in the vast majority of subjects and, when they were detectable their concentration was contained of the administered dose of Lantus.

In clinical studies, subgroup analyses based on historic period and gender did not signal any departure in safe and efficacy in insulin glargine-treated patients compared to the entire report population.

Paediatric population

Pharmacokinetics in children anile ii to less than half-dozen years with type 1 diabetes mellitus was assessed in one clinical study (see section v.ane). Plasma "trough" levels of insulin glargine and its main M1 and M2 metabolites were measured in children treated with insulin glargine, revealing plasma concentration patterns similar to adults, and providing no evidence for accumulation of insulin glargine or its metabolites with chronic dosing.

Not-clinical information reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential, toxicity to reproduction.

Zinc chloride

Metacresol

Glycerol

Hydrochloric acid (for pH adjustment)

Sodium hydroxide (for pH adjustment)

Water for injections

This medicinal product must non exist mixed with other medicinal products.

Lantus 100 units/ml solution for injection in a cartridge

iii years.

Shelf-life later first apply of the cartridge

The medicinal product may be stored for a maximum of 4 weeks not above thirty°C and away from direct rut or straight calorie-free.

The pen containing a cartridge or the pens in use must not be stored in the refrigerator.

The pen cap must be put back on the pen after each injection in society to protect from light.

Unopened cartridges

Store in a refrigerator (2°C-viii°C).

Practise not freeze or place next to the freezer compartment or a freezer pack.

Continue the cartridge in the outer carton in order to protect from light.

In-use cartridges

For storage conditions after showtime opening of this medicinal production, see department half-dozen.3.

Type 1 colourless glass cartridge with a blackness plunger (bromobutyl condom) and a flanged cap (aluminium) with a stopper (bromobutyl or laminate of polyisoprene and bromobutyl rubber) containing 3 ml of solution.

Packs of i, 3, iv, 5, 6, 8, ix and 10 cartridges.

Not all pack sizes may exist marketed

Inspect Lantus before apply. It must only be used if the solution is clear, colourless, with no solid particles visible, and if it is of water-like consistency. Since Lantus is a solution, it does not require resuspension before use.

Lantus must not be mixed with any other insulin or diluted. Mixing or diluting tin can change its time/activity profile and mixing can cause precipitation.

Insulin label must always exist checked before each injection to avoid medication errors between insulin glargine and other insulins (see section 4.4).

Insulin pen

Lantus 100 units/ml in cartridges is only suitable for subcutaneous injections from a reusable pen. If assistants past syringe is necessary, a vial should be used. The Lantus cartridges are to exist used only in conjunction with the pens: ClikSTAR, Autopen 24, Tactipen, AllStar, AllStar PRO or JuniorSTAR (see section 4.two and iv.4). Non all of these pens may be marketed in your country.

The pen should exist used equally recommended in the information provided by the device manufacturer.

The manufacturer's instructions for using the pen must exist followed carefully for loading the cartridge, attaching the needle, and administering the insulin injection.

If the insulin pen is damaged or not working properly (due to mechanical defects) it has to exist discarded, and a new insulin pen has to be used.

Cartridge

Before insertion into the pen, the cartridge must be stored at room temperature for 1 to two hours.

Air bubbling must be removed from the cartridge before injection (see instructions for using the pen). Empty cartridges must non be refilled.

Aventis Pharma Limited

410 Thames Valley Park Drive

Reading

Berkshire

RG6 1PT

UK

Trading every bit:

Sanofi

410 Thames Valley Park Bulldoze

Reading

Berkshire

RG6 1PT

Great britain

PLGB 04425/0815

Date of first authorisation: nine June 2000

Engagement of CAP conversion: 01 Janurary 2021

Date of latest renewal: 17 February 2015

01 Janurary 2021