Basaglar

/ Eli Lilly

Basaglar is a biosimilar medicinal product. Detailed information is available on the website of the Ministry of Health http://www.health.gov.il/hozer/dr_127.pdf
Basaglar contains insulin glargine, an insulin analogue and has a prolonged duration of action.
Basaglar should be administered once daily at any time but at the same time each day. The Basaglar dose regimen (dose and timing) should be individually adjusted. In patients with type 2 diabetes mellitus, Basaglar can also be given together with orally active antidiabetic medicinal products.
The potency of this medicinal product is stated in units. These units are exclusive to insulin glargine and are not the same as IU or the units used to express the potency of other insulin analogues.
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: Basaglar is not intended for use in children and adolescents under 18 years old.
Safety and efficacy of insulin glargine have been established in adolescents and children aged 2 years and older. Safety and efficacy of insulin glargine have not been established in children below the age of 2 years. No data are available.
Transition from other insulins to Basaglar: When changing from a treatment regimen with an intermediate or long-acting insulin to a regimen with Basaglar, a change of the dose of the basal insulin may be required and the concomitant
antidiabetic treatment may need to be adjusted (dose and timing of additional regular insulins or fastacting insulin analogues or the dose of oral antidiabetic medicinal products).
To reduce the risk of nocturnal and early morning hypoglycaemia, patients who are changing their basal insulin regimen from a twice daily NPH insulin to a once daily regimen with Basaglar should reduce their daily dose of basal insulin by 20-30 % during the first weeks of treatment.
During the first weeks the reduction should, at least partially, be compensated by an increase in mealtime insulin, after this period the regimen should be adjusted individually.
As with other insulin analogues, patients with high insulin doses because of antibodies to human insulin may experience an improved insulin response with Basaglar.
Close metabolic monitoring is recommended during the transition 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 be required, for example, if the patient’s weight or life-style changes, change of timing of insulin dose or other circumstances arise that increase susceptibility to hypoglycaemia or hyperglycaemia.
Method of administration: Basaglar is administered subcutaneously.
Basaglar should not be administered intravenously. The prolonged duration of action of insulin glargine 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 insulin glargine. Injection sites must be rotated within a given injection area from one injection to the next.
Basaglar must not be mixed with any other insulin or diluted. Mixing or diluting can change its time/action profile and mixing can cause precipitation.
Before using Basaglar KwikPen, the instructions for use included in the package leaflet must be read carefully.

Treatments of adult patients 18 years and over with type 1 or type 2 diabetes mellitus who require basal (long acting) insulin for the control of hyperglycaemia.

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

Basaglar is not the insulin of choice for the treatment of diabetic ketoacidosis. Instead, regular insulin administered intravenously is recommended in such cases.
In case of insufficient glucose control or a tendency to hyperglycaemic or hypoglycaemic episodes, the patient’s adherence to the prescribed treatment regimen, injection sites and proper injection technique and all other relevant factors must be reviewed before dose adjustment is considered.
Transferring a patient to another type or brand of insulin should be done under strict medical supervision. Changes in strength, brand (manufacturer), type (regular, NPH, lente, long-acting, etc.), origin (animal, human, human insulin analogue) and/or method of manufacture may result in the need for a change in dose.
Insulin administration may cause insulin antibodies to form. 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.
Hypoglycaemia: The time of occurrence of hypoglycaemia depends on the action profile of the insulins used and may, therefore, change when the treatment regimen is changed. Due to more sustained basal insulin supply with insulin glargine, less nocturnal but more early morning hypoglycaemia can be expected.
Particular caution should be exercised, and intensified blood glucose monitoring is advisable in patients in whom hypoglycaemic episodes might be of particular clinical relevance, such as in patients with significant stenoses of the coronary arteries or of the blood vessels supplying the brain (risk of cardiac or cerebral complications of hypoglycaemia) as well as in patients with proliferative retinopathy, particularly if not treated with photocoagulation (risk of transient amaurosis following hypoglycaemia).
Patients should be aware of circumstances where warning symptoms of hypoglycaemia are diminished. The warning symptoms of hypoglycaemia may be changed, be less pronounced or be absent in certain risk groups. These include patients:
– in whom glycaemic control is markedly improved,
– in whom hypoglycaemia develops gradually,
– who are elderly,
– after transfer from animal insulin to human insulin,
– in whom an autonomic neuropathy is present,
– with a long history of diabetes,
– suffering from a psychiatric illness,
– receiving concurrent treatment with certain other medicinal products.
Such situations may result in severe hypoglycaemia (and possibly loss of consciousness) prior to the patient’s awareness 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, correct insulin administration and awareness of hypoglycaemia symptoms are essential to reduce the risk of hypoglycaemia. Factors increasing the susceptibility to hypoglycaemia require particularly close monitoring and may necessitate dose
adjustment. These include:
– change in the injection area,
– improved insulin sensitivity (e.g., by removal of stress factors),
– unaccustomed, increased or prolonged physical activity,
– intercurrent illness (e.g. 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 certain other medicinal products.
Intercurrent illness: Intercurrent illness 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 often increased.
Patients with type 1 diabetes must continue to consume at least a small amount of carbohydrates on a regular basis, even if they are able to eat only little or no food, or are vomiting etc. and they must never omit insulin entirely.
Medication errors: Medication errors have been reported in which other insulins, particularly short-acting insulins, have been accidentally administered instead of insulin glargine. Insulin label must always be checked before each injection to avoid medication errors between Basaglar and other insulins.
Combination of Basaglar with pioglitazone: Cases of cardiac failure have been reported when pioglitazone was used in combination with insulin, especially in patients with risk factors for development of cardiac heart failure. This should be kept in mind if treatment with the combination of pioglitazone and Basaglar is considered. If the combination is used, patients should be observed for signs and symptoms of heart failure, weight gain and oedema.
Pioglitazone should be discontinued if any deterioration in cardiac symptoms occurs.
Excipients: This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e., essentially “sodium-free”.

Hypoglycaemia, in general the most frequent adverse reaction of insulin therapy, may occur if the insulin dose is too high in relation to the insulin requirement.
See prescribing information for full details.

A number of substances affect glucose metabolism and may require dose adjustment of insulin glargine.
Substances that may enhance the blood-glucose-lowering effect and increase susceptibility to hypoglycaemia include oral antidiabetic medicinal products, angiotensin converting enzyme (ACE) inhibitors, disopyramide, fibrates, fluoxetine, monoamine oxidase (MAO) inhibitors, pentoxifylline, propoxyphene, salicylates, somatostatin anologues and sulphonamide antibiotics.
Substances that may reduce the blood-glucose-lowering effect include corticosteroids, danazol, diazoxide, diuretics, glucagon, isoniazid, oestrogens, progestogens, phenothiazine derivatives, somatropin, sympathomimetic medicinal products (e.g. 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 potentiate or weaken the blood-glucose lowering effect of insulin. Pentamidine may cause hypoglycaemia, which may sometimes be followed by hyperglycaemia.
In addition, under the influence of sympatholytic medicinal products such as 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 1,000 pregnancy outcomes) indicate no specific adverse effects of insulin glargine on pregnancy and no specific malformative nor
feto/neonatal toxicity of insulin glargine. Animal data do not indicate reproductive toxicity.
The use of Basaglar may be considered during pregnancy, if necessary.
It is essential for patients with pre-existing or gestational diabetes to maintain good metabolic control throughout pregnancy to prevent adverse outcomes associated with hyperglycaemia. Insulin requirements may decrease during the first trimester and generally increase during the second and third trimesters. Immediately after delivery, insulin requirements decline rapidly (increased risk of hypoglycaemia). Careful monitoring of glucose control is essential.
Lactation: It is unknown whether insulin glargine is excreted in human milk. No metabolic effects of ingested insulin glargine on the breastfed newborn/infant are anticipated since insulin glargine as a peptide is digested into amino acids in the human gastrointestinal tract.
Breast-feeding women may require adjustments in insulin dose and diet.

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, meal patterns, or physical activity may be needed.
More severe episodes with coma, seizure, or neurologic impairment may be treated with intramuscular/subcutaneous glucagon or concentrated intravenous glucose. Sustained carbohydrate intake and observation may be necessary because hypoglycaemia may recur after apparent clinical recovery.

Storage: Before use: Store in a refrigerator (2°C -8°C). Do not freeze.
Do not store Basaglar next to the freezer compartment or a freezer pack.
Keep the pre-filled pen in the outer carton in order to protect from light.
In use: For storage conditions after first opening of this medicinal product, see section 6.3 at the attached doctor’s leaflet.
Shelf life: 2 years. Shelf life after first use: The medicinal product may be stored for a maximum of 28 days up to 30°C and away from direct heat or direct light. Pens in use must not be stored in the refrigerator. The pen cap must be put back on the pen after each injection in order to protect from light.