Insulin degludec interacts in the following cases:
Insulin degludec can be used in renal and hepatic impaired patients. Glucose monitoring is to be intensified and the insulin dose adjusted on an individual basis.
Alcohol may intensify or reduce the hypoglycaemic effect of insulin.
The following substances may reduce the insulin requirement: oral antidiabetic medicinal products, GLP-1 receptor agonists, monoamine oxidase inhibitors (MAOI), beta-blockers, angiotensin converting enzyme (ACE) inhibitors, salicylates, anabolic steroids and sulfonamides.
Beta-blockers may mask the symptoms of hypoglycaemia.
The following substances may increase the insulin requirement: oral contraceptives, thiazides, glucocorticoids, thyroid hormones, sympathomimetics, growth hormone and danazol.
Octreotide/lanreotide may either increase or decrease the insulin requirement.
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 insulin degludec 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.
The use of insulin degludec in pregnant women with diabetes has been investigated in an interventional trial. 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 insulin degludec 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 insulin degludec 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.
Insulin degludec 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 insulin degludec, 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.
Injection site reactions (including injection site haematoma, pain, haemorrhage, erythema, nodules, swelling, discolouration, pruritus, warmth and injection site mass) occurred in patients treated with insulin degludec. These reactions are usually mild and transitory and they normally disappear during continued treatment.
Insulin degludec has been administered to children and adolescents up to 18 years of age for the investigation of pharmacokinetic properties. 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.
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.
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