Levemir

/ Novo Nordisk

The potency of insulin analogues, including insulin detemir, is expressed in units, whereas the potency of human insulin is expressed in international units. 1 unit insulin detemir corresponds to 1 international unit of human insulin. Insulin detemir can be used alone as the basal insulin or in combination with bolus insulin. It can also be used in combination with oral antidiabetic medicinal products and/or GLP-1 receptor agonists.
When Insulin detemir is used in combination with oral antidiabetic medicinal products or when added to GLP-1 receptor agonists it is recommended to use Insulin detemir once daily, initially at a dose of 0.1-0.2 units/kg or of 10 units in adult patients. The dose of Insulin detemir should be titrated based on the individual patient’s needs.
When a GLP-1 receptor agonist is added to Insulin detemir, it is recommended to reduce the dose of Insulin detemir by 20% to minimise the risk of hypoglycaemia. Subsequently, dosage should be adjusted individually.
For individual dose adjustments, the following two titration guidelines are recommended for adults: See prescribing information for full details.
When Insulin detemir is used as part of a basal-bolus insulin regimen, Insulin detemir should be administered once or twice daily depending on patients’ needs. The dose of Insulin detemir should be adjusted individually. Adjustment of dose may be necessary if patients undertake increased physical activity, change their usual diet or during concomitant illness. When adjusting dose in order to improve glucose control, patients should be advised to be aware of signs of hypoglycaemia.
Special populations
Older people (≥ 65 years old): Insulin detemir can be used in older patients. In older patients, glucose monitoring should be intensified and the Insulin detemir dose adjusted on an individual basis.
Renal and hepatic impairment: Renal or hepatic impairment may reduce the patient’s insulin requirements. In patients with renal or hepatic impairment, glucose monitoring should be intensified and the Insulin detemir dose adjusted on an individual basis.
Paediatric population: Insulin detemir can be used in adolescents and children from the age of 2 years. When changing basal insulin to Insulin detemir, dose reduction of basal and bolus insulin needs to be considered on an individual basis, in order to minimise the risk of hypoglycaemia. In children and adolescents, glucose monitoring should be intensified and the Insulin detemir dose adjusted on an individual basis. The safety and efficacy of Insulin detemir in children below the age of 2 years have not been established.
Transfer from other insulin medicinal products: When transferring from other intermediate or long-acting insulin medicinal products, adjustment of the dose and timing of administration may be necessary. Close glucose monitoring is recommended during the transfer and in the initial weeks thereafter. Concomitant antidiabetic treatment may need to be adjusted (dose and/or timing of oral antidiabetic medicinal products or concurrent short/rapid-acting insulin medicinal products).
Method of administration:
Levemir® is a long-acting insulin analogue used as a basal insulin. Levemir® is for subcutaneous administration only. Levemir® must not be administered intravenously, as it may result in severe hypoglycaemia. Intramuscular administration should also be avoided. Levemir® is not to be used in insulin infusion pumps.
Levemir® is administered subcutaneously by injection in the abdominal wall, the thigh, the upper arm, the deltoid region or the gluteal region. Injection sites should always be rotated within the same region in order to reduce the risk of lipodystrophy. The duration of action will vary according to the dose, injection site, blood flow, temperature and level of physical activity. The injection can be given at any time during the day, but at the same time each day. For patients who require twice daily dosing to optimise blood glucose control, the evening dose can be administered in the evening or at bedtime.
For detailed user instructions, please refer to the package leaflet.
Levemir® Penfill®: Administration with an insulin delivery system:
Levemir® Penfill® is designed to be used with Novo Nordisk insulin delivery systems and NovoFine® or NovoTwist® needles. Levemir® Penfill® is only suitable for subcutaneous injections from a reusable pen. If administration by syringe is necessary, a vial should be used.
Levemir® FlexPen®: Administration with FlexPen®:
Levemir® FlexPen® is a pre-filled pen (colour-coded) designed to be used with NovoFine® or NovoTwist® disposable needles up to a length of 8 mm. FlexPen® delivers 1–60 units in increments of 1 unit. Levemir® FlexPen® is only suitable for subcutaneous injections. If administration by syringe is necessary, a vial should be used.

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

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

Before travelling between different time zones, the patient should seek the doctor’s advice since this may mean that the patient has to take the insulin and meals at different times.
Hyperglycaemia: Inadequate dosing or discontinuation of treatment, especially in type 1 diabetes, may lead to hyperglycaemia and diabetic ketoacidosis. Usually the first symptoms of hyperglycaemia develop gradually over a period of hours or days. They include thirst, increased frequency of urination, nausea, vomiting, drowsiness, flushed dry skin, dry mouth, loss of appetite as well as acetone odour of breath. In type 1 diabetes, untreated hyperglycaemic events eventually lead to diabetic ketoacidosis, which is potentially lethal.
Hypoglycaemia: Omission of a meal or unplanned, strenuous physical exercise may lead to hypoglycaemia. In children, care should be taken to match insulin doses (especially in basal-bolus regimens) with food intake and physical activities in order to minimise the risk of hypoglycaemia. Hypoglycaemia may occur if the insulin dose is too high in relation to the insulin requirement. In case of hypoglycaemia or if hypoglycaemia is suspected, Insulin detemir must not be injected. After stabilisation of the patient’s blood glucose, adjustment of the dose should be considered.
Patients whose blood glucose control is greatly improved, e.g. by intensified insulin therapy, may experience a change in their usual warning symptoms of hypoglycaemia, and should be advised accordingly. Usual warning symptoms may disappear in patients with longstanding diabetes. Concomitant illness, especially infections and feverish conditions, usually increases the patient’s insulin requirements. Concomitant diseases in the kidney, liver or affecting the adrenal, pituitary or thyroid gland can require changes in insulin dose. When patients are transferred between different types of insulin medicinal products, the early warning symptoms of hypoglycaemia may change or become less pronounced than those experienced with their previous insulin. Transfer from other insulin medicinal products. Transferring a patient to another type or brand of insulin should be done under strict medical supervision. Changes in strength, brand (manufacturer), type, origin (animal insulin, human insulin or insulin analogue) and/or method of manufacture (recombinant DNA versus animal source insulin) may result in the need for a change in dose. Patients transferred to Insulin Detemir   from another type of insulin may require a change in dose from that used with their usual insulin medicinal products. If an adjustment is needed, it may occur with the first dose or during the first few weeks or months.
Injection site reactions: As with any insulin therapy, injection site reactions may occur and include pain, redness, hives, inflammation, bruising, swelling and itching. Continuous rotation of the injection site within a given area may help to reduce or prevent these reactions. Reactions usually resolve in a few days to a few weeks. On rare occasions, injection site reactions may require discontinuation of Insulin Detemir.
Hypoalbuminaemia: There are limited data in patients with severe hypoalbuminaemia. Careful monitoring is recommended in these patients.
Combination of Insulin Detemir 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 Insulin Detemir   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.
See prescribing information for full details.

Hypoglycemia.
See prescribing information for full details.

A number of medicinal products are known to interact with the glucose metabolism. The following substances may reduce the patient’s insulin requirements: Oral antidiabetic medicinal products, GLP-1 receptor agonists, monoamine oxidase inhibitors (MAOI), beta-blockers, angiotensin converting enzyme (ACE) inhibitors, salicylates, anabolic steroids and sulphonamides. The following substances may increase the patient’s insulin requirements: Oral contraceptives, thiazides, glucocorticoids, thyroid hormones, sympathomimetics, growth hormone and danazol. Beta-blockers may mask the symptoms of hypoglycaemia. Octreotide/lanreotide may either increase or decrease the insulin requirement. Alcohol may intensify or reduce the hypoglycaemic effect of insulin.

Pregnancy:Treatment with Insulin detemir can be considered during pregnancy, but any potential benefit must be weighed against a possibly increased risk of an adverse pregnancy outcome.
In general, intensified blood glucose control and monitoring of pregnant women with diabetes are recommended throughout pregnancy and when contemplating pregnancy. Insulin requirements usually fall in the first trimester and increase subsequently during the second  and third trimester. After delivery, insulin requirements normally return rapidly to pre-pregnancy values.
Lactation: It is unknown whether insulin detemir is excreted in human milk. No metabolic effects of ingested insulin detemir on the breast-fed newborn/infant are anticipated since insulin detemir, as a peptide, is digested into amino acids in the human gastrointestinal tract. Breast-feeding women may require adjustments in insulin dose and diet.
See prescribing information for full details.

A specific overdose for insulin cannot be defined, however, hypoglycaemia may develop over sequential stages if too high doses relative to the patient’s requirement are administered: Mild hypoglycaemic episodes can be treated by oral administration of glucose or sugary products. It is therefore recommended that the diabetic patient always carries sugar-containing products. Severe hypoglycaemic episodes, where the patient has become unconscious, can be treated with glucagon (0.5 to 1 mg) given intramuscularly or subcutaneously by a trained person, or with glucose given intravenously by a healthcare professional. Glucose must be given intravenously, if the patient does not respond to glucagon within 10 to 15 minutes. Upon regaining consciousness, administration of oral carbohydrates is recommended for the patient in order to prevent a relapse.

Storage: Before opening: Store in a refrigerator (2°C – 8°C). Keep away from the cooling element. Do not freeze. During use or when carried as a spare: Store below 30°C. Do not refrigerate. Do not freeze. Use within 6 weeks after first opening. Keep the cap on FlexPen® in order to protect it from light.
Compatibility: Substances added to this drug  may cause degradation of insulin detemir, e.g. if the medicinal product contains thiols or sulphites. This drug  should not be added to infusion fluids. This medicinal product must not be mixed with other medicinal products.