Epipen junior

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT EPIPEN JUNIOR (EPIPEN JUNIOR)

Composition:

Active substance: adrenaline (epinephrine);

1 ml of solution contains 0.5 mg of adrenaline; 1 dose (0.3 ml) contains 0.15 mg of adrenaline;

Excipients: sodium chloride, sodium metabisulfite (E 223), concentrated hydrochloric acid, water for injections.

Pharmaceutical form. Solution for injection.

Main physicochemical characteristics: clear solution without visible particles.

Pharmacotherapeutic group. Cardiac drugs. Non-glycoside cardiotonics. Adrenergic and dopaminergic agents. Epinephrine. ATC code: C01C A24.

Pharmacological properties.

Pharmacodynamics. Epinephrine is a catecholamine that stimulates the sympathetic nervous system (alpha- and beta-receptors), thereby increasing heart rate, cardiac output, and enhancing coronary blood flow.

The action of epinephrine on beta-receptors in bronchial smooth muscle causes relaxation, which alleviates wheezing and reduces shortness of breath.

Epinephrine is rapidly inactivated, with the majority of the dose excreted in the urine as metabolites.

Pharmacokinetics. Epinephrine is a naturally occurring substance produced by the adrenal medulla in response to stress or physical exertion. It is rapidly inactivated primarily by two enzymes: catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO). Significant amounts of these enzymes are present in the liver, which plays an important, but not primary, role in its metabolism. Most of the administered dose of epinephrine is excreted in the urine as metabolites.

The plasma half-life of epinephrine is 2.5 minutes. However, following subcutaneous or intramuscular administration, local vasoconstriction delays absorption, resulting in a prolonged therapeutic effect that exceeds the expected half-life. Therefore, massage of the injection site is recommended.

In a pharmacokinetic study involving 35 healthy volunteers grouped according to varying degrees of subcutaneous fat thickness in the thigh and stratified by sex, a single dose of 0.3 mg/0.3 mL was administered to the outer thigh using the pre-filled Epipen auto-injector and compared in a crossover design with the same dose administered via a manual syringe with needles specifically adapted for intramuscular delivery. Results showed that in female subjects with a thick subcutaneous fat layer (skin-to-muscle distance under maximum compression > 20 mm), epinephrine absorption was slower, reflected by a trend toward lower plasma epinephrine concentrations during the first ten minutes after administration (see section "Special precautions for use"). However, overall epinephrine exposure from 0 to 30 minutes (AUC0–30 min) in all groups using the pre-filled Epipen auto-injector exceeded exposure after syringe administration. Importantly, the observed trend toward higher plasma epinephrine concentrations following administration via the pre-filled Epipen auto-injector compared to manual intramuscular injection in healthy subjects with well-perfused subcutaneous tissue may not necessarily be extrapolated to patients diagnosed with anaphylactic shock, in whom blood may be shunted away from the skin toward leg muscles. Therefore, the potential for cutaneous vasoconstriction during injection should be considered.

Inter-patient and intra-individual variability was relatively high in this study; therefore, definitive conclusions cannot be drawn.

Clinical characteristics.

Indications. Severe allergic reactions (anaphylaxis), for example: allergic reactions to insect stings, food, medications, contact with other allergens, as well as idiopathic anaphylaxis or anaphylaxis triggered by physical exertion.

Contraindications. There are no known absolute contraindications for the use of EpiPen Junior in emergency treatment of allergic reactions.

Interaction with other medicinal products and other forms of interaction. Use with caution in patients taking medications that may cause cardiac arrhythmia, including cardiac glycosides and quinidine. The effect of adrenaline may be enhanced when used concomitantly with tricyclic antidepressants, monoamine oxidase inhibitors (MAO inhibitors), catechol-O-methyltransferase (COMT) inhibitors, thyroid hormones, theophylline, oxytocin, parasympatholytics, certain antihistamines (diphenhydramine, chlorpheniramine), levodopa, and alcohol.

Adrenaline inhibits insulin secretion, thereby increasing blood glucose levels. Diabetic patients receiving adrenaline may require an increased dose of insulin or oral hypoglycemic agents.

Caution! Beta-stimulating effects may be reduced during concomitant therapy with beta-blockers.

The risk of developing arrhythmias is increased when adrenaline is used concomitantly with cardiac glycosides, quinidine, tricyclic antidepressants, dopamine, inhalational anesthetics (enflurane, halothane, isoflurane, methoxyflurane), and cocaine.

Concomitant use of adrenaline with other sympathomimetic agents may enhance adverse cardiovascular effects.

Concomitant use of adrenaline with antihypertensive agents (including diuretics) may reduce their effectiveness.

Concomitant use of adrenaline with monoamine oxidase inhibitors (including furazolidone, procarbazine, selegiline) may result in sudden and pronounced increase in blood pressure, hyperpyretic crisis, headache, cardiac arrhythmias, and vomiting.

Concomitant use of adrenaline with thyroid hormone preparations may result in mutual enhancement of effects.

Concomitant use of adrenaline with astemizole, cisapride, or terfenadine may result in QT interval prolongation on ECG.

Concomitant use of adrenaline with ergot alkaloids may enhance vasoconstrictor effects, leading to marked ischemia and development of gangrene.

Concomitant use of adrenaline with hypoglycemic agents (including insulin) may reduce the hypoglycemic effect.

Special precautions for use.

All patients prescribed EPIPEN JUNIOR should be carefully instructed to understand the indications for use and to learn the correct method of administration. It is strongly recommended to also train the patient's immediate contacts (e.g., parents, caregivers, teachers) in the proper use of the EPIPEN JUNIOR auto-injector to ensure adequate support in emergency situations.

Patients should be informed that emergency medical assistance must be called immediately in the event of anaphylactic shock. After administration of the first dose, immediate medical attention is required for thorough medical evaluation and further treatment if necessary.

The medicinal product is administered intramuscularly into the anterolateral aspect of the thigh. Patients should be informed that the injection must not be given into the buttock.

When administering the injection to another person, the patient's leg should be firmly held still to minimize the risk of needle bending, leg injury, or other trauma.

The pre-filled pen is intended for single use only, and under no circumstances should a used pen be reused.

Adrenaline should be used with particular caution in patients with cardiovascular disorders, as well as in patients with diabetes mellitus, hyperthyroidism, arterial hypertension, and elderly patients. Its use should only be considered when the potential benefit outweighs the risk, and only under medical supervision. Adverse reactions may occur in patients with elevated intraocular pressure, severe renal insufficiency, benign prostatic hyperplasia causing urinary retention, hypercalcemia, and hypokalemia. In patients with Parkinson's disease, epinephrine may temporarily exacerbate symptoms such as rigidity and tremor.

The patient and their caregiver should be informed about the possibility of biphasic anaphylaxis, characterized by initial symptom improvement followed by recurrence of symptoms several hours later.

Patients with concomitant asthma may be at increased risk of severe anaphylactic reactions.

Cases of accidental injection into the muscles of the arms or legs have been reported, leading to peripheral ischemia. In the event of accidental injection, the patient should seek medical advice for appropriate treatment.

In patients with a thick subcutaneous fat layer, adrenaline may fail to reach the muscle tissue and may not produce an optimal effect. Therefore, there is a risk that a single dose of EPIPEN JUNIOR may be insufficient, and a repeat injection may be necessary.

EPIPEN JUNIOR contains sodium metabisulfite, which may rarely cause severe hypersensitivity reactions, including anaphylactic shock and bronchospasm, particularly in individuals with asthma. Patients with such conditions should carefully read the instructions for medical use before administering EPIPEN JUNIOR.

One dose of the medicinal product contains less than 1 mmol of sodium (23 mg), i.e., it is practically "sodium-free".

Patients should be advised about potential allergens, and, if possible, testing should be performed to identify their specific allergens.

Use during pregnancy or breastfeeding.

Pregnancy. Clinical experience with use in pregnant women is limited. Adrenaline should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Breastfeeding. There is no biologically available oral form of adrenaline; any amount of adrenaline in breast milk is not expected to have harmful effects on the breastfed infant.

Reproductive function. Since adrenaline is a substance naturally produced in the body, the medicinal product is not expected to have harmful effects on fertility.

Ability to influence reaction speed when driving or operating machinery. During treatment with this medicinal product, driving vehicles or operating machinery is not recommended, as patients may experience symptoms of anaphylactic shock.

Method of administration and dosage.

Dosage

Children with body weight from 15 kg to 30 kg

The usual recommended dose is 0.15 mg, administered intramuscularly.

Children with body weight less than 15 kg

The medication is not intended for children with body weight less than 15 kg.

The medication should be used at the first signs of anaphylactic shock.

If there is no clinical improvement or if the condition worsens after the first injection, a second injection may be administered. The repeat injection should be given approximately 5–15 minutes after the first. Therefore, patients are advised to always carry two pre-filled Epipen Junior auto-injectors with them.

After administration of the medication, the patient must consult a physician for appropriate follow-up measures, further examination and/or further treatment.

The physician must ensure that the patient understands the indications for use and the correct way to use the Epipen Junior medication.

The physician should thoroughly instruct the patient on the package insert for medical use, proper administration technique, and possible symptoms of anaphylactic shock.

Method of administration

Epipen Junior is intended for immediate use in patients at risk of anaphylactic shock, as well as in patients with a history of anaphylactic reactions.

The medication is administered intramuscularly into the outer thigh. The medication must not be injected into the buttocks. The medication can be administered through clothing or subcutaneously.

Use and disposal

Check the solution through the viewing window of the pre-filled pen: the solution should be clear and colorless. Do not use the pre-filled pen if the solution is discolored or contains a precipitate. Do not use after the expiration date.

Each pre-filled pen contains 2 mL of adrenaline injection 0.5 mg/mL, delivering a single dose (0.3 mL) of 0.15 mg adrenaline. After use, 1.7 mL of the substance remains in the pre-filled pen.

Under no circumstances should you touch the orange tip of the Epipen Junior pre-filled pen with fingers or hands. Cases of accidental injection into the finger or hand have been reported, leading to peripheral ischemia. The medication in the Epipen Junior pre-filled pen should be administered into the outer thigh. The injection is activated immediately when the orange tip contacts the skin or another surface.

blue protective cap viewing window orange tip

Follow the instructions below only when you are ready to use the pre-filled pen.

Hold the pre-filled pen only in the middle; do not hold it by the end. For proper injection, follow these instructions:

• Do not cover the orange tip with fingers or hands. Do not press the orange tip with fingers or hands.
• Remember that the needle extends from the orange tip.
• Do not remove the blue protective cap until you are ready to use the pre-filled pen.

A small amount of air bubbles in the prefilled pen is acceptable and does not affect the effectiveness of the medication.

After using the medication, a significant amount of liquid (approximately 90%) will remain, which must not be reused.

However, if the viewing window is obscured and the orange tip is extended, you have received the required dose of medication. After use, place the prefilled pen back into its carrier tube and keep it with you when visiting a doctor, hospital, or pharmacy.

Since EpiPen Jr is used for emergency medical treatment, call emergency medical services immediately after administration, specifying the diagnosis of "anaphylaxis."

Inform the physician about the intramuscular injection of adrenaline or show the packaging and/or the package leaflet/instructions for medical use of the medication.

Until emergency medical services arrive, the patient should lie down with legs elevated, unless this causes breathing difficulties—in which case the patient should sit up. The patient must remain under supervision until emergency help arrives, in case symptoms recur.

Unconscious patients should be placed in a stable lateral position.

In case of overdose or accidental injection of adrenaline, seek immediate medical assistance.

Children.

EpiPen Jr is intended for use in children weighing between 15 kg and 30 kg.

For children weighing less than 15 kg, a dose lower than 0.15 mg is not recommended due to the difficulty in accurately calculating the dose.

For children weighing more than 30 kg, EpiPen containing 0.3 mg of adrenaline should be used.

Overdose.

Overdose or accidental intravascular injection of adrenaline may lead to intracranial hemorrhage due to a sudden increase in blood pressure. Fatal outcomes may result from pulmonary edema caused by peripheral vasoconstriction combined with cardiac stimulation.

Pulmonary edema can be counteracted with alpha-blocking agents such as phentolamine. Beta-blockers should be administered in cases of arrhythmia.

Adverse reactions.

Adverse effects are associated with the action of adrenaline on alpha- and beta-adrenergic receptors and include symptoms such as tachycardia and arterial hypertension, as well as adverse reactions from the central nervous system.

Criteria for assessing the frequency of adverse drug reactions:

Infections and infestations: Frequency unknown – infection at the injection site. In post-marketing studies, rare cases of serious skin and soft tissue infections have been reported, including necrotizing fasciitis and myonecrosis caused by Clostridia (gas gangrene).

Psychiatric disorders: Frequency unknown – anxiety.

Nervous system disorders: Frequency unknown – headache, dizziness, tremor.

Cardiovascular system disorders: Rare – stress cardiomyopathy; frequency unknown – tachycardia, cardiac arrhythmia, palpitations, angina pectoris, ventricular fibrillation, arterial hypertension, pallor, peripheral ischemia, which may occur following accidental injection into the muscles of the arms or legs.

Respiratory, thoracic and mediastinal disorders: Frequency unknown – dyspnea.

Gastrointestinal disorders: Frequency unknown – nausea, vomiting.

Skin and subcutaneous tissue disorders: Frequency unknown – increased sweating.

General disorders and administration site conditions: Frequency unknown – fatigue; accidental injections may lead to injuries such as hematoma, bruising, discoloration, erythema, or bone injury.

Shelf life. 19 months.

Storage conditions. Keep out of reach and sight of children. Store below 25°C in the original packaging to protect from light. Do not freeze.

Incompatibilities.

Adrenaline and its salts are rapidly destroyed in solution by oxidizing agents. The solution may darken upon exposure to air or light.

Packaging. 2 ml of injectable solution in a pre-filled pen; 1 pre-filled pen in a carton.

Prescription category. Prescription only.

Manufacturer. MEDA Pharma GmbH & Co. KG.

Manufacturer's name and address.
Benzstrasse 1, 61352 Bad Homburg, Germany.