ZEGALOGUE Solution for injection Ref.[115117] Active ingredients: Dasiglucagon

Glycogen stores and hypoglycaemia

Dasiglucagon is effective in treating hypoglycaemia only if sufficient liver glycogen is present. To prevent relapse of the hypoglycaemia, oral carbohydrates should be given to restore liver glycogen, when the patient has responded to treatment. Patients in states of starvation, with adrenal insufficiency, chronic alcohol abuse or chronic hypoglycaemia may not have adequate levels of hepatic glycogen for dasiglucagon administration to be effective. Patients with these conditions should be treated with glucose.

Phaeocromocytoma

Glucagon stimulates the release of catecholamines. In the presence of phaeocromocytoma, glucagon products can cause the tumour to release large amounts of catecholamines, which will cause an acute hypertensive reaction. Zegalogue is contraindicated in patients with phaeochromocytoma (see section 4.3).

Insulinoma

In patients with insulinoma, administration of glucagon medicinal products may produce an initial increase in blood glucose. However, dasiglucagon administration may directly or indirectly (through an initial rise in blood glucose) stimulate exaggerated insulin release from an insulinoma and cause hypoglycaemia. A patient developing symptoms of hypoglycaemia after a dose of dasiglucagon should be given glucose orally or intravenously.

Excipients

This medicinal product contains less than 1 mmol sodium (23 mg) per dose (0.6 mL), that is to say essentially ‘sodium-free’.

Latex

In latex-sensitive individuals the medicinal product may cause severe allergic reactions.

Dasiglucagon does not inhibit CYP enzymes and drug transporters in vitro at clinically relevant concentrations.

Insulin

Reacts antagonistically towards dasiglucagon.

Indometacin

When used with indometacin, dasiglucagon may lose its ability to raise blood glucose or may even produce hypoglycaemia.

Warfarin

Dasiglucagon may increase the anticoagulant effect of warfarin.

Beta-blockers

Patients taking beta-blockers might be expected to have a greater increase in both pulse and blood pressure when taking dasiglucagon, an increase of which will be transient because of the short half-life of dasiglucagon. The increase in blood pressure and pulse rate may require therapy in patients with coronary artery disease.

Pregnancy

There are no data from the use of dasiglucagon, a glucagon analogue, in pregnant women. The use of glucagon has been reported in pregnant women with diabetes and no harmful effects are known with respect to the course of pregnancy and the health of the unborn and the neonate.

Studies in animals with dasiglucagon have shown reproductive toxicity (see section 5.3). Untreated hypoglycaemia in pregnancy can cause complications and may be fatal.

The use of Zegalogue during pregnancy should be considered only if the expected benefit justifies the potential risk to the foetus.

Breast-feeding

Dasiglucagon is cleared from the bloodstream very quickly and thus the amount excreted in the milk of nursing mothers following treatment of severe hypoglycaemic reactions is expected to be extremely small. As dasiglucagon is degraded in the digestive tract and cannot be absorbed in its intact form, it will not exert any metabolic effect in the child. Zegalogue can be used during breast-feeding.

Fertility

Based on animal data, dasiglucagon had no effect on male or female fertility (see section 5.3).

Zegalogue has no or neglible influence on the ability to drive and use machines.

The patient’s ability to concentrate and react may be impaired as a result of hypoglycaemia which may persist for a brief period after receiving treatment. This may present a risk in situations where these abilities are especially important, such as driving or using machines.

Summary of the safety profile

The most frequently reported adverse reactions are nausea (62.2%), vomiting (31.6%) and headache (9.6%).

Tabulated list of adverse reactions

Adverse reactions associated with dasiglucagon obtained from clinical studies are tabulated below. Adverse reactions associated with dasiglucagon are listed by system organ class and frequency. Frequency categories are defined as: 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); not known (cannot be estimated from the available data).

Table 1. Tabulated list of adverse reactions associated with dasiglucagon:

Description of selected adverse reactions

Hypersensitivity reactions, including anaphylactic reactions have been observed with injectable glucagon and reported as ‘very rare’ (less than 1 case per 10 000 patients) and are known medicinal class effects of glucagon.

Paediatric population

Safety results in a limited paediatric population of 20 patients aged 7-17 years old, in a placebo-controlled trial were consistent with the safety profile in adults, except for nausea (65%) and vomiting (50%), which were less frequent in adults.

Reporting of suspected adverse reactions

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.

Not applicable.