Source: European Medicines Agency (EU) Revision Year: 2022 Publisher: Novo Nordisk A/S, Novo Allé, DK-2880 Bagsværd, Denmark
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Omission of a meal or unplanned strenuous physical exercise may lead to hypoglycaemia.
Hypoglycaemia may occur if the insulin dose is too high in relation to the insulin requirement (see sections 4.5, 4.8 and 4.9).
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.
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 must be advised accordingly. Usual warning symptoms may disappear in patients with long-standing diabetes.
Concomitant illness, especially infections and fever, usually increases the patient’s insulin requirement. Concomitant diseases in the kidney, liver or diseases affecting the adrenal, pituitary or thyroid gland may require changes in the insulin dose.
As with other basal insulin products, the prolonged effect of Tresiba may delay recovery from hypoglycaemia.
Administration of rapid-acting insulin is recommended in situations with severe hyperglycaemia.
Inadequate dosing and/or discontinuation of treatment in patients requiring insulin may lead to hyperglycaemia and potentially to diabetic ketoacidosis. Furthermore, concomitant illness, especially infections, may lead to hyperglycaemia and thereby cause an increased insulin requirement.
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, and loss of appetite as well as acetone odour of breath. In type 1 diabetes mellitus, untreated hyperglycaemic events eventually lead to diabetic ketoacidosis, which is potentially lethal.
Transferring a patient to another type, brand or manufacturer of insulin must be done under medical supervision and may result in the need for a change in dosage.
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 risk 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 area has been reported to result in hypoglycaemia. Blood glucose monitoring is recommended after the change in the injection site from an affected to an unaffected area, and dose adjustment of antidiabetic medications may be considered.
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 failure. This should be kept in mind if treatment with the combination of pioglitazone and Tresiba 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.
Intensification of insulin therapy with abrupt improvement in glycaemic control may be associated with temporary worsening of diabetic retinopathy, while long-term improved glycaemic control decreases the risk of progression of diabetic retinopathy.
Patients must be instructed to always check the insulin label before each injection to avoid accidental mix-ups between the two different strengths of Tresiba as well as other insulin products.
Patients must visually verify the dialled units on the dose counter of the pen. Therefore, the requirement for patients to self-inject is that they can read the dose counter on the pen. Patients who are blind or have poor vision must be instructed to always get help/assistance from another person who has good vision and is trained in using the insulin device.
To avoid dosing errors and potential overdose, patients and healthcare professionals should never use a syringe to draw the medicinal product from the cartridge in the pre-filled pen. In the event of blocked needles, patients must follow the instructions described in the instructions for use accompanying the package leaflet (see section 6.6).
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.
This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e. it is essentially ‘sodium-free’.
In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.
A number of medicinal products are known to interact with glucose metabolism.
Oral antidiabetic medicinal products, GLP-1 receptor agonists, monoamine oxidase inhibitors (MAOI), beta-blockers, angiotensin converting enzyme (ACE) inhibitors, salicylates, anabolic steroids and sulfonamides.
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.
The use of Tresiba in pregnant women with diabetes has been investigated in an interventional trial (see section 5.1). A moderate amount of clinical trial and post-marketing data in pregnant women (more than 400 pregnancy outcomes) indicate no malformative or feto/neonatal toxicity. Animal reproduction studies have not revealed any difference between insulin degludec and human insulin regarding embryotoxicity and teratogenicity.
The treatment with Tresiba may be considered during pregnancy, if clinically needed.
In general, intensified blood glucose control and monitoring of pregnant women with diabetes are recommended throughout pregnancy and when contemplating pregnancy. Insulin requirements usually decrease in the first trimester and increase subsequently during the second and third trimesters. After delivery, insulin requirements usually return rapidly to pre-pregnancy values. Careful monitoring of glucose control is recommended and the insulin dose adjusted on an individual basis.
There is no clinical experience with Tresiba during breast-feeding. In rats, insulin degludec was secreted in milk; the concentration in milk was lower than in plasma.
It is unknown whether insulin degludec is excreted in human milk. No metabolic effects are anticipated in the breast-fed newborn/infant.
Animal reproduction studies with insulin degludec have not revealed any adverse effects on fertility.
This medicinal product has no or negligible influence on the ability to drive and use machines. However, the patient’s ability to concentrate and react may be impaired as a result of hypoglycaemia. This may constitute a risk in situations where these abilities are of special importance (e.g. driving a car or using machines).
Patients must be advised to take precautions to avoid hypoglycaemia while driving. This is particularly important in those who have reduced or absent awareness of the warning signs of hypoglycaemia or have frequent episodes of hypoglycaemia. The advisability of driving should be considered in these circumstances.
The most frequently reported adverse reaction during treatment is hypoglycaemia (see section ‘Description of selected adverse reactions’ below).
Adverse reactions listed below are based on clinical trial data and classified according to MedDRA System Organ Class. Frequency categories are defined according to the following convention: 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) and not known (cannot be estimated from the available data).
| System organ class | Frequency | Adverse reaction |
|---|---|---|
| Immune system disorders | Rare | Hypersensitivity Urticaria |
| Metabolism and nutrition disorders | Very common | Hypoglycaemia |
| Skin and subcutaneous tissue disorders | Uncommon | Lipodystrophy |
| Not known | Cutaneous amyloidosis† | |
| General disorders and administration site conditions | Common | Injection site reactions |
| Uncommon | Peripheral oedema |
† ADR from postmarketing sources.
With insulin preparations, allergic reactions may occur. Immediate-type allergic reactions to either insulin itself or the excipients may potentially be life-threatening.
With Tresiba, hypersensitivity (manifested with swelling of tongue and lips, diarrhoea, nausea, tiredness and itching) and urticaria were reported rarely.
Hypoglycaemia may occur if the insulin dose is too high in relation to the insulin requirement. Severe hypoglycaemia may lead to unconsciousness and/or convulsions and may result in temporary or permanent impairment of brain function or even death. The symptoms of hypoglycaemia usually occur suddenly. They may include cold sweats, cool pale skin, fatigue, nervousness or tremor, anxiousness, unusual tiredness or weakness, confusion, difficulty in concentration, drowsiness, excessive hunger, vision changes, headache, nausea and palpitation.
Lipodystrophy (including lipohypertrophy, lipoatrophy) and cutaneous amyloidosis may occur at the injection site and delay local insulin absorption. Continuous rotation of the injection site within the given injection area may help to reduce or prevent these reactions (see section 4.4).
Injection site reactions (including injection site haematoma, pain, haemorrhage, erythema, nodules, swelling, discolouration, pruritus, warmth and injection site mass) occurred in patients treated with Tresiba. These reactions are usually mild and transitory and they normally disappear during continued treatment.
Tresiba has been administered to children and adolescents up to 18 years of age for the investigation of pharmacokinetic properties (see section 5.2). Safety and efficacy have been demonstrated in a long term trial in children aged 1 to less than 18 years. The frequency, type and severity of adverse reactions in the paediatric population do not indicate differences to the experience in the general diabetes population (see section 5.1).
Based on results from clinical trials, the frequency, type and severity of adverse reactions observed in elderly and in patients with renal or hepatic impairment do not indicate any differences to the broader experience in the general population.
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.
This medicinal product must not be mixed with any other medicinal products.
Substances added to Tresiba may cause degradation of insulin degludec.
Tresiba must not be added to infusion fluids.
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