Insulin detemir

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.

Alcohol may intensify or reduce the hypoglycaemic effect of insulin.

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.

Beta-blockers may mask the symptoms of hypoglycaemia.

The following substances may increase the patient’s insulin requirements: 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 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.

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.

In an open-label randomised controlled clinical trial pregnant women with type 1 diabetes (n=310) were treated in a basal-bolus treatment regimen with insulin detemir (n=152) or NPH insulin (n=158) as basal insulin, both in combination with NovoRapid. Primary objective of this study was to assess the effect of insulin detemir on blood glucose regulation in pregnant women with diabetes.

The overall rates of maternal adverse events were similar for insulin detemir and NPH insulin treatment groups; however, a numerically higher frequency of serious adverse events in the mothers (61 (40%) vs. 49 (31%)) and in the newborn children (36 (24%) vs. 32 (20%)) was seen for insulin detemir compared to NPH insulin. The number of live born children of women becoming pregnant after randomisation were 50 (83%) for insulin detemir and 55 (89%) for NPH. The frequency of congenital malformations was 4 (5%) for insulin detemir and 11 (7%) for NPH with 3 (4%) major malformations for insulin detemir and 3 (2%) for NPH.

Post-marketing data from an additional 250 outcomes from pregnant women exposed to insulin detemir indicate no adverse effects of insulin detemir on pregnancy and no malformative or foetal/neonatal toxicity of insulin detemir.

Animal data do not indicate reproductive toxicity.

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.

Fertility

Animal studies do not indicate harmful effects with respect to fertility.

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 operating machinery).

Patients should 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.