GlucaGen Hypokit

Glucagon.

One vial contains 1 mg glucagon as hydrochloride corresponding to 1 mg (1 IU) glucagon/ml after reconstitution.
Before reconstitution, the compacted powder should be white or nearly white. The solvent should be clear and colourless without particles.
Active substance: Human glucagon produced in Saccharomyces cerevisiae by recombinant DNA technology.
Excipients/Inactive Ingredients: Lactose monohydrate, Hydrochloric acid for pH adjustment, Sodium hydroxide for pH adjustment, Water for injections.
The reconstituted solution contains lactose monohydrate 107 mg/ml.

Pharmacotherapeutic group: Pancreatic hormones, Glycogenolytic hormones. ATC code: H04AA01.
Pharmacology: Pharmacodynamics: Mechanism of action: Glucagon is a hyperglycaemic agent that mobilises hepatic glycogen, which is released into the blood as glucose.
Glucagon inhibits the tone and motility of the smooth muscle in the gastrointestinal tract.
Pharmacodynamic effects: When used in treatment of severe hypoglycaemia, an effect on blood glucose is usually seen within 10 minutes.
The onset of inhibitory effect on gastrointestinal motility occurs within 1 minute after an intravenous injection. Duration of action is in the range 5-20 minutes depending on the dose. The onset of effect occurs within 5-15 minutes after an intramuscular injection, with a duration of 10-40 minutes.
Pharmacokinetics: Metabolism: Glucagon is degraded enzymatically in the blood plasma and in the organs to which it is distributed. The liver and kidney are major sites of glucagon clearance, each organ contributing about 30% to the overall metabolic clearance rate.
Elimination: Glucagon has a short half-life in the blood of about 3-6 minutes. Metabolic clearance rate of glucagon in humans is approximately 10 ml/kg/min.
Toxicology: Preclinical safety data: No relevant pre-clinical data exist that provide information useful to the prescriber.

Therapeutic indication: GlucaGen is indicated for treatment of severe hypoglycaemic reactions, which may occur in the management of insulin-treated children and adults with diabetes mellitus.
Diagnostic indication: GlucaGen is indicated for motility inhibition in examinations of the gastrointestinal tract in adults.

Posology: Therapeutic indication (Severe hypoglycaemia): Dosage for adult patients: Administer 1 mg by subcutaneous or intramuscular injection.
Special populations: Paediatric population (<18 years old): GlucaGen can be used for the treatment of severe hypoglycaemia in children and adolescents.
Dosage for paediatric patients: Children below 25 kg or younger than 8 years: Administer 0.5 mg.
Children above 25 kg or older than 8 years: Administer 1.0 mg.
Elderly (≥65 years old): GlucaGen can be used in elderly patients.
Renal and hepatic impairment: GlucaGen can be used in patients with renal and hepatic impairment.
Diagnostic indication (Inhibition of gastrointestinal motility): Dosage for adult patients: The diagnostic dose for relaxation of the stomach, duodenal bulb, duodenum and small bowel is 0.2-0.5 mg given as intravenous injection or 1 mg given intramuscularly; the dose to relax the colon is 0.5-0.75 mg intravenously or 1-2 mg intramuscularly.
Special populations: Paediatric population (<18 years old): The safety and efficacy of GlucaGen for inhibition of gastrointestinal motility in children and adolescents have not been established. No data are available.
Elderly (≥65 years old): GlucaGen can be used in elderly patients.
Renal and hepatic impairment: GlucaGen can be used in patients with renal and hepatic impairment.
Method of administration: Dissolve the compacted powder in the accompanying solvent, as described in Instruction for use, handling and disposal under Cautions for Usage.
Therapeutic indication (Severe hypoglycaemia): Administer by subcutaneous or intramuscular injection. The patient will normally respond within 10 minutes. When the patient has responded to the treatment, give oral carbohydrates to restore the liver glycogen and prevent relapse of hypoglycaemia. If the patient does not respond within 10 minutes, intravenous glucose should be given.
Diagnostic indication (Inhibition of gastrointestinal motility): GlucaGen must be administered by medical personnel. Onset of action after an intravenous injection of 0.2-0.5 mg occurs within one minute and the duration of effect is between 5 and 20 minutes. The onset of action after an intramuscular injection of 1-2 mg occurs after 5-15 minutes and lasts approximately 10-40 minutes.
After the end of the diagnostic procedure, oral carbohydrates should be given if this is compatible with the diagnostic procedure applied.

In the case of overdose, the patient may experience nausea and vomiting. Due to the short half-life of glucagon, these symptoms will be transient.
In case of dosages substantially above the approved range, the serum potassium may decrease and should be monitored and corrected, if needed.

Hypersensitivity to the active substance or to any of the excipients listed in Description.
Phaeochromocytoma.

Due to the instability of GlucaGen in solution, the product should be given immediately after reconstitution and must not be given as an intravenous infusion.
Therapeutic indication: 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.
The tip cap of the syringe included in the GlucaGen HypoKit contains natural rubber latex which may cause allergic reactions in latex-sensitive individuals.
Diagnostic indication: Persons who have been given glucagon in connection with diagnostic procedures may experience discomfort, in particular if they have been fasting. Nausea, hypoglycaemia, and blood pressure changes have been reported in these situations. After the end of a diagnostic procedure, oral carbohydrates should be given to patients who have been fasting, if this is compatible with the diagnostic procedure applied. If fasting is needed post-examination or in case of severe hypoglycaemia, glucose given intravenously may be required.
Glucagon reacts antagonistically towards insulin and caution should be observed if GlucaGen is used in patients with insulinoma. Caution should also be observed in patients with glucagonoma.
Caution should be observed when GlucaGen is used as an adjunct in endoscopic or radiographic procedures in diabetic patients or in elderly patients with known cardiac disease.
Glucagon stimulates the release of catecholamines. In the presence of phaeochromocytoma, glucagon can cause the tumour to release large amounts of catecholamines, which will cause an acute hypertensive reaction. Glucagon is contraindicated in patients with phaeochromocytoma (see Contraindications).
Effects on 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.
After diagnostic procedures, hypoglycaemia has been reported infrequently. Therefore, driving a vehicle and operating machinery should be avoided until the patient has had a meal with oral carbohydrates.

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. GlucaGen can be used during pregnancy.
Breast-feeding: Glucagon is cleared from the bloodstream very fast (mainly by the liver) (t_1/2 = 3-6 min.); thus, the amount excreted in the milk of nursing 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. GlucaGen can be used during breast-feeding.
Fertility: Animal reproduction studies have not been conducted with GlucaGen. Studies in rats have shown that glucagon does not cause impaired fertility.

Summary of the safety profile: Severe adverse reactions are very rare, although nausea, vomiting and abdominal pain may occur occasionally. Hypersensitivity reactions, including anaphylactic reactions, have been reported as 'very rare' (less than 1 case per 10,000 patients). When used in the diagnostic indication, hypoglycaemia/hypoglycaemic coma has been reported, especially in patients who have fasted. Cardiovascular adverse events, such as tachycardia and blood pressure changes have only been reported when GlucaGen is used as an adjunct in endoscopic or radiographic procedures.
Tabulated summary of adverse reactions: Frequencies of undesirable effects considered related to treatment with GlucaGen during clinical trials and/or post-marketing surveillance are presented as follows. Undesirable effects which have not been observed in clinical trials, but have been reported spontaneously, are presented as 'very rare'. During marketed use, reporting of adverse drug reactions is very rare (<1/10,000). However, post-marketing experience is subject to under-reporting and this reporting rate should be interpreted in that light.
Therapeutic indication: Immune system disorders: Very rare (<1/10,000): Hypersensitivity reactions including anaphylactic reaction/shock.
Gastrointestinal disorders: Common (≥1/100 to <1/10): Nausea.
Uncommon (≥1/1,000 to <1/100): Vomiting.
Rare (≥1/10,000 to <1/1,000): Abdominal pain.
Paediatric population: Based on data from clinical trials and post-marketing experience, the frequency, type and severity of adverse reactions observed in children are expected to be the same as in adults.
Other special populations: Based on 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.
Additional side effects after use in diagnostic procedures: Metabolism and nutrition disorders: Uncommon (≥1/1,000 to <1/100): Hypoglycaemia: After a diagnostic procedure, this could be more pronounced in patients that have fasted (see Precautions).
Very rare (<1/10,000): Hypoglycaemic coma.
Cardiovascular disorders: Very rare (<1/10,000): Tachycardia, hypotension, hypertension: Cardiovascular adverse events have only been reported when GlucaGen is used as an adjunct in endoscopic or radiographic procedures.
Paediatric population: There are no data available on the diagnostic use of GlucaGen in children.
Other special populations: Based on 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.

Insulin: Reacts antagonistically towards glucagon.
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.
Interactions between GlucaGen and other drugs are not known when GlucaGen is used in the approved indications.

Instruction for use, handling and disposal: Reconstitution: The reconstituted GlucaGen should be used immediately after preparation.
1. Remove the plastic cap from the vial. Pull the needle cover off the syringe. Do not remove the plastic back-stop from the syringe. Insert the needle through the rubber stopper (within the marked circle) of the vial containing GlucaGen and inject all the liquid from the syringe into the vial.
2. Without taking the needle out of the vial, gently shake the vial until GlucaGen has completely dissolved, and the solution is clear.
3. Make sure the plunger is completely down. While keeping the needle in the liquid, slowly withdraw all the solution back into the syringe. Do not pull the plunger out of the syringe. See How much to use as follows.
4. Make an air shot and inject.
How much to use: The usual dosage for severe hypoglycaemia: Adults and children above 25 kg or older than 8 years: 1 ml, marked as 1.0 on the syringe.
Children below 25 kg or younger than 8 years: ½ ml, marked as 0.5 on the syringe.
Note that a syringe with a thinner needle and a finer graduation may be more suitable for use in diagnostic procedures.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
Incompatibilities: There are no known incompatibilities with GlucaGen.

Do not freeze.
If, in rare cases, the reconstituted product shows any signs of fibril formation (viscous appearance) or insoluble matter, it should be discarded.
Store below 25°C and in the original package in order to protect from light.

Other Agents Affecting Metabolism

H04AA01 - glucagon ; Belongs to the class of glycogenolytic hormones. Used in the treatment of hypoglycemia.

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