OGLUO Solution for injection Ref.[50398] Active ingredients: Glucagon

Glycogen stores and hypoglycaemia

To prevent relapse of the hypoglycaemia, oral carbohydrates should be given to restore the liver glycogen, when the patient has responded to the treatment.

Glucagon will not be effective in patients whose liver glycogen is depleted. For that reason, glucagon has little or no effect when the patient has been fasting for a prolonged period, or is suffering from adrenal insufficiency, chronic hypoglycaemia, or alcohol induced hypoglycaemia.

Glucagon, unlike adrenaline, has no effect upon muscle phosphorylase and therefore cannot assist in the transference of carbohydrate from the much larger stores of glycogen that are present in the skeletal muscle.

Insulinoma

In patients with insulinoma, administration of glucagon may produce an initial increase in blood glucose. However, glucagon 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 glucagon should be given glucose orally or intravenously.

Caution should also be observed in patients with glucagonoma.

Recovery time

Please take into account that approximately 15% of patients achieved glucose recovery after 20 minutes or more in the pivotal trial.

No interaction studies have been performed.

Insulin

Insulin reacts antagonistically towards glucagon.

Indomethacin

When used with indomethacin, glucagon may lose its ability to raise blood glucose or paradoxically, may even produce hypoglycaemia.

Warfarin

Glucagon 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, an increase of which will be temporary because of glucagon’s short half-life. The increase in blood pressure and pulse rate may require therapy in patients with coronary artery disease.

Pregnancy

Glucagon does not cross the human placenta barrier. 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. Ogluo can be used during pregnancy.

Breast-feeding

Glucagon is cleared from the bloodstream very fast (mainly by the liver) (t_1/2= 3–6 minutes); thus the amount excreted in the milk of breast-feeding mothers following treatment of severe hypoglycaemic reactions is expected to be extremely small. As glucagon is degraded in the digestive tract and cannot be absorbed in its intact form, it will not exert any metabolic effect in the child. Ogluo can be used during breast-feeding.

Fertility

Animal reproduction studies have not been conducted with Ogluo. Studies in rats have shown that glucagon does not cause impaired fertility.

Ogluo has negligible influence on the ability to drive and use machines.

After a severe hypoglycaemic event, the patient’s ability to concentrate and react may be impaired; therefore the patient should not drive or operate machinery after a severe hypoglycaemic event until the patient has stabilised.

Summary of the safety profile

The most frequently reported adverse reactions are nausea (30%) and vomiting (16%).

Tabulated list of adverse reactions

Frequencies of adverse reactions considered related to treatment with Ogluo during clinical trials are presented below. The adverse drug reactions are classified according to the System Organ Class. Frequency groups are defined by 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 available data). Within each frequency group, adverse reactions are presented in order of decreasing seriousness.

Table 1. Frequency of adverse reactions of glucagon injection:

Description of selected adverse reactions

The most frequently reported adverse reactions are nausea (43%), vomiting (13%), and headache (5%). Adverse reactions are mild to moderate in severity and resolved on their own. No serious adverse reactions have been related to glucagon.

Hypersensitivity reactions, including anaphylactic reactions, have been reported as ‘very rare’ (<1/10,000 patients) with injectable glucagon. These are known medicinal product class effects of glucagon.

Paediatric population

The most frequently reported adverse reactions are nausea (48%), vomiting (19%), hyperglycaemia (7%), and headache (7%). Hypoglycaemia (42%) was observed in clinical trials but was not considered related to glucagon. The most frequently reported adverse reactions observed by age group are presented below.

Table 2. Frequency of most common adverse reactions among paediatric populations:

Other special populations

Efficacy and safety data for Ogluo are very limited in patients aged 65 years and absent in patients aged 75 and above, in or pregnant patients, or patients with hepatic or renal impairment. Based upon data from clinical trials and post-marketing experience,the frequency, type, and severity of adverse reactions observed in elderly patients and in patients with renal or hepatic impairment are expected to be the same as in the general population.

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.