What is Abasaglar?
- Insulin is made in the pancreas. Insulin ensures that glucose (carbohydrates) from food ends up in the body’s cells and is not left behind in blood.
- In diabetes mellitus (diabetes). In diabetes there is too much glucose in the blood. This is harmful to the heart and blood vessels, nerves, eyes and kidneys.
- Complaints about too much glucose in the blood: thirst, drinking a lot, often urinating, fatigue and lethargy.
- Short-acting insulins work within 10 to 30 minutes, 2 to 8 hours long. Medium-acting insulins within 1-2 hours, 16 to 24 hours. Long-acting insulins work within 1-2 hours, 24 hours.
- You will receive instructions on syringes, using the insulin pen or insulin pump and testing glucose in the blood yourself with a blood glucose meter and test strips.
- The most important side effect of insulin is a hypo. You then have too little glucose in your blood. You notice that hunger, pale skin, trembling, sweating, dizziness, headaches, fatigue and fainting.
- Treat a hypo immediately by eating some grape sugar or drinking a sugary drink. Then eat a sandwich. Make sure someone can spray glucagon and call a doctor when you are no longer approachable due to a hypo.
Abasaglar Injection indication and Uses
Treatment of diabetes mellitus in adults, adolescents and children from 2 years.
- Abasaglar Injection contains insulin glargine, an insulin analogue, and has a prolonged duration of action.
- Abasaglar Injection should be administered once a day at any time of the day but at the same time each day.
- The dosage regimen of Abasaglar Injection (dosage and timing of administration) should be adjusted individually. In patients with type 2 diabetes, Abasaglar Injection may also be used with oral antidiabetic agents.
- The activity of this medicine is expressed in units. These units are specific to insulin glargine and do not correspond to the IUs or units used for other insulin analogues .
Elderly (≥ 65 years old)
- In elderly patients, progressive impairment of renal function may cause a steady decrease in insulin requirements.
- In patients with renal impairment, insulin requirements may be decreased due to a reduction in insulin metabolism.
- In patients with hepatic impairment, insulin requirements may be decreased due to a reduction in the ability of gluconeogenesis and a reduction in insulin metabolism.
- The safety and efficacy of insulin glargine has been established in adolescents and children from 2 years of age. The available data are detailed under the headingsUndesirable effects , Pharmacodynamic properties and Pharmacokinetic properties .
- The safety and efficacy of insulin glargine have not been studied in children under 2 years of age. No data available.
Transition of other insulins to Abasaglar Injection
- When replacing an intermediate-acting or long-acting insulin with Abasaglar Injection, it may be necessary to change the insulin dose and / or adjust the dosage of concomitant antidiabetic therapy (doses and schedules of administration of fast insulins or rapid analogues of insulin or dosages of the associated oral antidiabetic agents).
- To reduce the risk of early night or early morning hypoglycemia, patients who replace their basal insulin regimen with 2 daily injections of NPH insulin with a daily injection of Abasaglar Injection should reduce their daily dose. basal insulin 20-30% during the first weeks of treatment.
- During the first weeks, this reduction must, at least in part, be offset by an increase in insulin covering meals, after this period the treatment will have to be adjusted individually.
- As with other insulin analogues, patients requiring high doses of insulin due to the presence of human insulin antibodies may experience an improvement in their insulin response with Abasaglar Injection.
- Close metabolic monitoring is recommended during the transition period and the first few weeks after. If there is an improvement in metabolic balance and therefore an increase in insulin sensitivity, it may be necessary to perform additional dosage adjustment. Dosage adjustment may also be required, for example, in the event of changes in body weight or lifestyle of the patient, changes in the time of administration of insulin, or any other circumstances that may increase susceptibility to hypo- or hyperglycemia (see Warnings and Precautions for Use section ).
- Abasaglar Injection is administered subcutaneously.
- Abasaglar Injection ne doit pas être administré par voie intraveineuse. L’effet prolongé de l’insuline glargine dépend de l’injection dans le tissu sous-cutané. L’administration intraveineuse de la dose sous-cutanée usuelle risquerait de provoquer une hypoglycémie sévère.
- Il n’a pas ete observe de differences cliniques notables sur le plan des taux seriques d’insuline et de glucose, selon que l’insuline glargine soit administree dans l’abdomen, la region deltoïde ou la cuisse. Il faut neanmoins effectuer une rotation des sites d’injection dans une même zone d’injection, d’une injection à l’autre.
- Abasaglar Injection should not be mixed with another insulin or diluted. Mixing or dilution may alter the action profile as a function of time and mixing may cause precipitation.
- For more details on handling, see the section Instructions for use, handling and disposal.
- The instructions for use mentioned in the package leaflet should be read carefully before using Abasaglar Injection KwikPen ( see section Instructions for use, handling and disposal).
- Hypersensitivity insulin glargine
- Metacresol hypersensitivity
- Route IV
Hypersensitivity to the active substance or to any of the excipients listed in the Composition section.
How it works Abasaglar Injection
Pharmacotherapeutic group: Drugs used in diabetes, insulins and long-acting injectable analogues.
ATC Code: A10AE04.
Abasaglar Injection is a biosimilar drug. Detailed information is available on the website of the European Medicines Agency
- Insulin glargine is a poorly soluble human insulin analogue with a neutral pH. It is completely soluble at the acidic pH of Abasaglar Injection solution for injection (pH 4). After injection into the subcutaneous tissue, the acid solution is neutralized, which induces the formation of micro-precipitates from which small amounts of insulin glargine are released continuously. As a result, the concentration / time curve is smooth, without peaks, predictable, and the duration of action is prolonged.
- Insulin glargine is metabolised to 2 active metabolites M1 and M2 .
Receptor binding of insulin
- In vitro studies indicate that the affinity of insulin glargine and its M1 and M2 metabolites for the human insulin receptor is similar to that of human insulin.
- IGF-1 receptor binding: Insulin glargine affinity for the human IGF-1 receptor is approximately 5 to 8 times greater than that of human insulin (but approximately 70 to 80 times lower than that of IGF-1), whereas M1 and M2 bind to the IGF-1 receptor with a slightly lower affinity than that of human insulin.
- The total therapeutic insulin concentration (insulin glargine and its metabolites) observed in type 1 diabetic patients was significantly lower than would be required to achieve half of the maximal IGF-1 receptor occupancy and activation. of the mitogenic (proliferative) pathway by the IGF-1 receptor. The physiological concentrations of endogenous IGF-1 can activate the mitogenic (proliferative) pathway, but the therapeutic concentrations observed during insulin treatment, especially during treatment with Abasaglar Injection, are considerably lower than the pharmacological concentrations necessary to activate the pathway. of IGF-1.
- The main effect of insulin, including insulin glargine, is to regulate glucose metabolism. Insulin and its analogs decrease blood glucose by stimulating peripheral uptake of glucose, particularly in skeletal muscle and adipose tissue, and by inhibiting hepatic glucose production. Insulin inhibits lipolysis in the adipocyte, inhibits proteolysis and stimulates protein synthesis.
- Clinical pharmacology studies have shown that identical doses of insulin glargine and human insulin administered intravenously are equipotent. As with all insulins, physical activity and other parameters may affect the time course of action of insulin glargine.
- Euglycemic clamp studies in healthy subjects and patients with type 1 diabetes showed that the effect of subcutaneous insulin glargine appeared to be slower than that of human NPH insulin, that this effect was consistent , without peaks, and that its duration of action was prolonged.
- This more prolonged effect of insulin glargine subcutaneously is directly related to the fact that resorption of this insulin is slower. As a result, only one administration per day is sufficient. The effect profile of insulin and insulin analogues such as insulin glargine may vary considerably from subject to subject and subject.
- In a clinical study, symptoms of hypoglycaemia and compensatory hormonal responses were similar after intravenous administration of insulin glargine and human insulin in both healthy volunteers and patients with type 1 diabetes.
Efficacy and clinical safety
- The effects of insulin glargine (1 injection per day) on diabetic retinopathy were evaluated over 5 years in a controlled open-label versus NPH study (administered twice daily) in 1024 patients with type 2 diabetes and whose progression Retinopathy of 3 points or more on the Early Treatment Diabetic Retinopathy Study (ETDRS) scale was investigated by fundus photography. No significant difference was observed in the progression of diabetic retinopathy when insulin glargine was compared to NPH insulin.
- ORIGIN (Outcome Reduction with Initial Glargine Intervention) was a multicentre, randomized, 2×2 factorial design in 12,537 patients with high cardiovascular (CV) risk who had either fasting glucose abnormality or glucose intolerance (12). % of patients), either type 2 diabetes treated with zero or oral diabetes medication (88% of patients). Patients were randomized (1: 1) to receive either insulin glargine (n = 6264), titrated to achieve fasting blood glucose ≤ 95 mg / dL (5.3 mmol / L), or standard (n = 6273).
- The first major efficacy endpoint was the time until a first CV-like event, non-fatal myocardial infarction or nonfatal stroke occurred. The second main co-criterion was the time until one of the events of the first primary co-criterion, or a revascularization procedure (coronary, carotid or peripheral), or a hospitalization for insufficiency occurred. heart.
- Secondary efficacy endpoints included all-cause mortality and a composite endpoint of microvascular involvement.
- Insulin glargine did not alter the relative risk of CV morbidity and mortality compared with standard therapy. No difference was observed between insulin glargine and standard treatment for the two co-primary efficacy endpoints, nor for each of the events evaluated separately in these two criteria, nor for all the causes of mortality, nor for the microvascular disorders.
- The average dose of insulin glargine at the end of the study was 0.42 U / kg. The median value of HbA1c was 6.4% at baseline, then this value under treatment was between 5.9% and 6.4% in the insulin glargine group and between 6.2% and 6%. , 6% in the standard treatment group for the duration of the follow-up.
- The rates of severe hypoglycaemia (number of patients per 100 patients per year of exposure) were 1.05 in the insulin glargine group and 0.30 in the standard treatment group; the rates of confirmed non-severe hypoglycaemia were 7.71 in the insulin glargine group and 2.44 in the standard treatment group. In this 6-year study, 42% of patients in the insulin glargine group never experienced hypoglycaemia.
- At the last follow-up visit, there was a mean increase in body weight of 1.4 kg in the insulin glargine group and an average decrease of 0.8 kg in the standard treatment group.
- In a randomized controlled clinical trial, children and adolescents (6-15 years) with type 1 diabetes (n = 349) were treated for 28 weeks with a basal / bolus regimen, with rapid human insulin before each meal . Insulin glargine was administered once a day at bedtime and human NPH insulin was administered once or twice daily. The effects on glycated hemoglobin and the incidence of symptomatic hypoglycaemia were similar between the two treatment groups, however the fasting blood glucose level decreased more than its initial value with insulin glargine compared with NPH insulin. . There was also less severe hypoglycaemia with insulin glargine. One hundred and forty-three of the patients treated with Insulin glargine in this study continued their treatment with insulin glargine during an uncontrolled extension of the study, with an average follow-up duration of 2 years. No new safety signals were identified during the extension of insulin glargine therapy.
- A cross-over study in 26 type-1 diabetic adolescents aged 12 to 18 comparing insulin glargine with insulin lispro to NPH insulin with human rapid insulin (each treatment being given for 16 weeks in a random order) was also conducted. As in the pediatric study described above, the reduction in fasting blood glucose from baseline was greater with insulin glargine than with NPH insulin. Variations of HbA1c compared to baseline were similar between the two treatment groups, however nighttime blood glucose values were significantly higher in the insulin glargine / insulin lispro group than in the insulin NPH / insulin group fast human, with an average nadir of 5.4 mmol / L against 4.1 mmol / L. As a result, the incidence of nocturnal hypoglycaemia was 32% in the insulin glargine / insulin lispro group versus 52% in the NPH insulin / human fast insulin group.
- A 24-week, parallel-group study was conducted in 125 type-1 diabetic children aged 2 to 6, comparing insulin glargine, once a day in the morning, with NPH insulin once or twice daily administered as basal insulin. Both groups received boluses of insulin before meals. The primary objective of demonstrating the non-inferiority of insulin glargine versus NPH on total hypoglycaemia was not achieved and the number of hypoglycemic events tended to be higher with insulin glargine [ratio of hypoglycaemia insulin glargine / NPH = 1.18 (95% CI: 0.97-1.44)]. Changes in glycated hemoglobin and blood glucose were comparable between the two treatment groups. No new tolerance signal
Abasaglar Injection Side Effects
Side effects usually have to do with underdosing or overdose.
The main side effects are the following.
- Too high blood glucose. If you do not inject enough insulin, your blood glucose level becomes too high ( hyper ); The characteristics of high blood glucose (more than ten mmol per liter) are: frequent urination, drinking a lot, thirst, dry tongue, fatigue and drowsiness.
- Too low amount of blood glucose. If you spray too much, your blood glucose will become too low ( hypo ). A too low amount of blood glucose can also be the result of great physical exertion, eating too little, eating too late or spraying insulin in a different body part than normal, for example belly instead of buttock. The insulin is then taken up too quickly and the amount of blood sugar decreases faster than normal. The characteristics of low blood glucose (less than three mmol per liter) are: hunger, paleness, shaking and sweating, varying mood, fatigue, dizziness and headache.
- The doctor or diabetes nurse will discuss with you how often you need to measure your blood glucose every day. The normal value is 4 to 10 mmol per liter. If you always tolerate your insulin well and still suddenly suffer from too high or too low blood glucose, then it is advisable to consult your doctor or pharmacist. Especially the hypo must be treated well, because otherwise you can lose your consciousness.
- Hypersensitivity is possible by the insulin or by additives such as the preservative. In the past, animal insulin was used, which often caused allergic reactions. Nowadays one is able to make ‘human’ insulin in the laboratory. This insulin is very similar to the human insulin, so allergic reactions (usually) are omitted. If you appear to be hypersensitive to this medicine, always report this to your pharmacist. The pharmacy team can then ensure that you do not get this (or a related) remedy.
- Spray spots . These are hard spots or bumps on the skin. If you notice this, please contact your doctor. DO NOT inject insulin into these areas. In these places the absorption of insulin is different. This can make your blood glucose fluctuate a lot. Spray marks usually disappear gradually if you stop spraying there.
- Blurred vision at the start of treatment. Your vision may also change in the first months. This is because your eyes have to get used to the changes in blood glucose. So wait preferably a few weeks with the fitting of a (new) reading glasses.
Abasaglar Injection Interactions
- Various substances affect glucose metabolism, which may require adjustment of the insulin glargine dose.
- Drugs that may cause an increase in hypoglycemic effect and sensitivity to hypoglycemia include oral antidiabetic drugs, ACE inhibitors, disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors (MAOIs), pentoxifylline, propoxyphene, salicylates, somatostatin analogues and sulfonamide antibiotics.
- Drugs that may reduce the hypoglycemic effect are, inter alia, corticosteroids, danazol, diazoxide, diuretics, glucagon, isoniazid, estrogens and progestins, phenothiazines, somatropin, sympathomimetic drugs [eg epinephrine (adrenaline), salbutamol, terbutaline], thyroid hormones, atypical antipsychotics (eg, clozapine and olanzapine) and protease inhibitors.
- Beta-blockers, clonidine, lithium salts and alcohol can either potentiate or attenuate the hypoglycemic effect of insulin. Pentamidine may cause hypoglycemia, sometimes followed by hyperglycemia.
- On the other hand, under the influence of sympatholytic agents such as beta-blockers, clonidine, guanethidine and reserpine, the signs of adrenergic compensatory reaction can be attenuated or absent.
Abasaglar Injection Warnings and Precautions
- Abasaglar Injection is not the insulin of choice for the treatment of diabetic ketoacidosis. In this situation, it is recommended to administer fast insulin intravenously.
- If the glycemic equilibrium is not optimal or if the patient tends to have hyperglycemic or hypoglycemic episodes, it must first be checked that the patient complies with the prescribed treatment, the sites and the appropriate technique of injection and the patient. all other relevant factors before considering adjusting the insulin dose.
- Any change in the type of insulin or brand of insulin must be done under strict medical control.
- The change in concentration, brand (manufacturer), type of insulin (fast, NPH, slow, long-acting, etc.), of origin (animal, human, human insulin analogue) and / or manufacturing method may require dose adjustment.
- Insulin administration may cause the formation of insulin antibodies. In rare cases, the presence of these insulin antibodies may make it necessary to adjust the insulin dose to correct a tendency to hypo- or hypoglycaemia (see section 4.8 ).
The time of onset of hypoglycemia depends on the action profile of the insulins used and can therefore change after modification of the treatment regimen. Due to a higher basal insulin intake with insulin glargine, a reduction in nocturnal hypoglycaemia and an increase in early morning hypoglycaemia can be expected.
Particular caution and intensification of blood glucose monitoring should be exercised in patients for whom the hypoglycemic episodes may have particularly serious clinical consequences, for example in cases of significant stenosis of the coronary or carotid arteries (risk of cardiac or cerebral complications). hypoglycemia), as well as proliferative retinopathy, especially if it is not treated with photocoagulation (risk of transient amaurosis after hypoglycaemia).
Patients should be aware of the circumstances in which the warning symptoms of hypoglycemia are alleviated. The warning symptoms of hypoglycaemia may be modified, attenuated or absent in certain risk groups, namely:
- in patients whose glycemic equilibrium has been significantly improved,
- if progressive hypoglycaemia is established,
- in elderly patients,
- after passage from animal insulin to human insulin
- in case of vegetative neuropathy,
- in long-term diabetic patients,
- in patients with psychiatric disorders,
- in patients receiving at the same time certain other drugs (see section Interactions with other medicinal products and other forms of interaction ).
In such situations, severe hypoglycaemia (possibly with loss of consciousness) may develop before the patient becomes aware of hypoglycaemia.
The prolonged effect of insulin glargine subcutaneously may delay the recovery of hypoglycaemia.
If the glycated hemoglobin level is normal or lowered, the possibility of recurrent hypoglycaemic episodes that have gone unnoticed (especially at night) should be mentioned.
To reduce the risk of hypoglycaemia, it is essential that the patient follow the dosing and dietary instructions, administer insulin correctly, and be aware of the symptoms of hypoglycaemia. Factors that increase susceptibility to hypoglycemia require particularly strict monitoring and may require dose adjustment. These factors are:
- change of injection zone,
- improvement of insulin sensitivity (for example, after elimination of stressors),
- unusual physical exercise, increased or prolonged,
- intercurrent illness (eg vomiting, diarrhea),
- differences in speed,
- omission of meals,
- taking alcohol,
- certain non-compensated disorders of the endocrine system (for example, hypothyroidism, hypopituitarism or adrenal insufficiency),
- joint administration of certain other drugs.
Any intercurrent illness requires enhanced metabolic monitoring. It is often advisable to look for the presence of ketone bodies in the urine and often need to adjust insulin doses. Insulin requirements are often increased. Patients with type 1 diabetes should continue to consume at least a small amount of carbohydrate regularly, even if they can not eat, or hardly eat, vomiting, etc. They must never stop insulin completely.
Pens to use with Abasaglar Injection cartridges
Cartridges should only be used with reusable pens recommended for use with Lilly insulin cartridges and should not be used with other reusable pens as the accuracy of the assay has not been established with other pens.
Medication errors have been reported in which other insulins, particularly fast-acting insulins, have been accidentally administered in place of insulin glargine. The insulin label should always be checked before each injection to avoid medication errors between Abasaglar Injection and other insulins.
Association of Abasaglar Injection with pioglitazone
Cases of heart failure have been reported when pioglitazone is associated with insulin, particularly in patients with risk factors for developing heart failure. This should be taken into account if a combination of Abasaglar Injection with pioglitazone is considered. If the combination is used, it is recommended to monitor the signs and symptoms of heart failure, weight gain and edema. Pioglitazone should be stopped in the presence of any deterioration of cardiac symptoms.
This medicine contains less than 1 mmol sodium (23 mg) per dose, ie it is essentially “sodium-free”.
Drive and use machines
Patients’ ability to concentrate and react may be impaired by hypoglycaemia or hyperglycemia or, for example, by visual disturbances. This can be a risk in situations where these faculties are of primary importance (eg driving or using machines).
Patients should be advised to take precautions before driving to avoid hypoglycaemia, especially if hypoglycemic warning symptoms are absent or reduced or if episodes of hypoglycaemia are common. The question is whether it is recommended to drive a vehicle or use a machine in these circumstances.
Abasaglar pen and Pregnancy / Breastfeeding / Fertility
- There are no data from controlled clinical studies on the use of insulin glargine in pregnant women. A high number of data in pregnant women (more than 1000 pregnancies) did not reveal any specific adverse effect of insulin glargine on pregnancy, nor any specific malformative effect, nor toxic to the fetus or the newborn insulin glargine.
- Studies in animals have not shown reproductive toxicity.
- The use of Abasaglar Injection may be considered during pregnancy if necessary.
- In case of pre-existing diabetes or gestational diabetes, it is imperative to maintain a good metabolic balance throughout pregnancy to prevent the occurrence of adverse effects related to hyperglycemia. Insulin requirements may decrease during the first trimester of pregnancy and generally increase during the second and third trimesters. Immediately after delivery, insulin requirements decrease rapidly (increased risk of hypoglycaemia). Careful monitoring of the glycemic balance is essential.
- It is not known whether insulin glargine is excreted in breast milk. No metabolic effects of insulin glargine ingested in neonates / breastfed infants are expected since insulin glargine, like any peptide, is digested into amino acids at the gastrointestinal level.
- Adjustment of insulin dose and diet may be necessary during breastfeeding.
- Studies in animals have not shown any direct deleterious effects on fertility.
What should I do if I miss a dose?
If you forget a dose, check your blood glucose level and still inject some insulin.
What happens if I overdose from Abasaglar Injection ?
- Overdose with insulin may cause severe hypoglycaemia, which may be prolonged and life-threatening.
- Episodes of mild hypoglycemia can usually be treated with oral carbohydrate. It may be necessary to adjust the dose of the drug, food intake or physical activity.
- More severe episodes, with coma, seizures or neurologic disturbances, may be treated with intramuscular or subcutaneous glucagon, or intravenous concentrated glucose. Since hypoglycaemia may recur after apparent clinical improvement, it may be necessary to continue carbohydrate intake and monitoring.
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