Epiject^® (Solution) Instructions for Use

Marketing Authorization Holder

Meda AB (Sweden)

Manufactured By

Meridian Medical Technologies, Inc. (USA)

Labeled By

MERIDIAN MEDICAL TECHNOLOGIES, Inc. (USA)

Or

Manufacturing Packaging Farmaca, MPF B.V. (Netherlands)

ATC Code

C01CA24 (Epinephrine)

Active Substance

Epinephrine (Rec.INN registered by WHO)

Dosage Form

Epiject®

Solution for intramuscular administration 0.3 mg/dose: 2 ml autoinjectors

Dosage Form, Packaging, and Composition

Solution for intramuscular administration as a clear, colorless or slightly yellowish liquid.

Excipients: sodium chloride – 1.8 mg, sodium disulfite – 0.5 mg, hydrochloric acid – to adjust pH to 3.6-4.1, water for injections – to 0.3 ml.

2 ml – autoinjectors (1) – plastic cases (1) – cardboard packs.

Clinical-Pharmacological Group

Alpha-, beta-adrenergic agonist

Pharmacotherapeutic Group

Alpha- and beta-adrenomimetic

Pharmacological Action

Adrenomimetic, has a direct stimulating effect on alpha- and beta-adrenergic receptors.

Under the action of epinephrine (adrenaline), stimulation of alpha-adrenergic receptors leads to an increase in intracellular calcium content in smooth muscles. Activation of alpha₁-adrenergic receptors increases phospholipase C activity (via G-protein stimulation) and the formation of inositol triphosphate and diacylglycerol. This promotes calcium release from the sarcoplasmic reticulum stores. Activation of alpha₂-adrenergic receptors leads to the opening of calcium channels and increased calcium entry into cells.

Stimulation of beta-adrenergic receptors causes G-protein-mediated activation of adenylate cyclase and increased cAMP formation. This process triggers responses from various target organs. Stimulation of beta₁-adrenergic receptors in heart tissue increases intracellular calcium. Stimulation of beta₂-adrenergic receptors decreases free intracellular calcium in smooth muscles, due to both increased transport out of the cell and its accumulation in the sarcoplasmic reticulum stores.

It has a pronounced effect on the cardiovascular system. Increases heart rate and strength, stroke volume and cardiac output. Improves AV conduction, increases automaticity. Increases myocardial oxygen demand. Causes vasoconstriction of abdominal organs, skin, mucous membranes, and to a lesser extent, skeletal muscles. Increases blood pressure (mainly systolic), in high doses increases systemic vascular resistance. The pressor effect can cause a short-term reflex decrease in heart rate.

Epinephrine (adrenaline) relaxes bronchial smooth muscles, reduces tone and motility of the gastrointestinal tract, dilates pupils, and helps reduce intraocular pressure. Causes hyperglycemia and increases plasma free fatty acid levels.

Pharmacokinetics

Metabolized by MAO and COMT in the liver, kidneys, and gastrointestinal tract. T_1/2 is several minutes. Excreted by the kidneys.

Penetrates the placental barrier, does not cross the blood-brain barrier.

Excreted in breast milk.

Indications

Immediate-type allergic reactions (including urticaria, angioneurotic shock, anaphylactic shock) developing from the use of medications, serums, blood transfusions, food consumption, insect bites, or exposure to other allergens.

Bronchial asthma (relief of an attack), bronchospasm during anesthesia.

Asystole (including against the background of acutely developed third-degree AV block).

Bleeding from superficial vessels of the skin and mucous membranes (including from the gums).

Arterial hypotension not responding to adequate volumes of replacement fluids (including shock, trauma, bacteremia, open-heart surgery, renal failure, chronic heart failure, drug overdose).

To prolong the action of local anesthetics.

Episodes of complete AV block (with the development of syncope (Morgagni-Adams-Stokes syndrome)).

Hypoglycemia (due to insulin overdose).

To stop bleeding.

ICD codes

Dosage Regimen

Administer Epiject^® via intramuscular injection into the anterolateral aspect of the thigh.

For anaphylaxis in adults and children weighing 30 kg or more, use the 0.3 mg dose.

For anaphylaxis in children weighing 15 kg to 30 kg, use the 0.15 mg dose.

Inject through clothing if necessary, avoiding seams and pockets where a button might be located.

Hold the auto-injector firmly against the thigh for a minimum of 10 seconds to ensure complete delivery.

Massage the injection area for 10 seconds after administration.

Seek immediate emergency medical attention after every use, even if symptoms appear to improve.

Repeat the dose after 5 to 15 minutes if symptoms persist or recur.

For severe, persistent anaphylaxis not responding to intramuscular injection, administer epinephrine via slow intravenous infusion under strict medical supervision.

Prepare the IV infusion by diluting 1 mg (1 mL) of epinephrine (1:1000) in 1000 mL of 0.9% sodium chloride, resulting in a 1:1,000,000 solution.

Initiate the IV infusion at a rate of 1 to 4 micrograms per minute (1-4 mL/min) and titrate to desired hemodynamic response.

For cardiac arrest, administer 1 mg (10 mL of a 1:10,000 solution) intravenously every 3 to 5 minutes during resuscitation.

For severe hypersensitivity reactions not involving full anaphylaxis, administer 0.1 to 0.25 mg subcutaneously or intramuscularly, repeated every 5 to 15 minutes as needed.

For prolongation of local anesthesia, add a concentration of 1:200,000 to 1:100,000 to the local anesthetic solution.

Do not inject into buttocks or digits.

Inspect the solution visually for particulate matter and discoloration prior to administration; do not use if the solution is discolored or contains particles.

Adverse Reactions

From the cardiovascular system: angina pectoris, bradycardia or tachycardia, palpitations, increase or decrease in blood pressure; when used in high doses – ventricular arrhythmias; rarely – arrhythmia, chest pain, pulmonary edema.

From the immune system angioedema, bronchospasm, skin rash, erythema multiforme.

From the digestive system nausea, vomiting.

From the nervous system headache, anxiety, tremor, tic, dizziness, nervousness, feeling of fatigue, psychoneurotic disorders (psychomotor agitation, disorientation, memory impairment, aggressive or panic behavior, schizophrenia-like disorders, paranoia), sleep disturbance, muscle twitching.

From the urinary system rarely – difficult and painful urination (with prostate hyperplasia).

Local reactions pain or burning at the intramuscular injection site.

Other hypokalemia, increased sweating.

Contraindications

Hypersensitivity to epinephrine; hypertrophic obstructive cardiomyopathy, tachyarrhythmia, ventricular fibrillation, chronic heart failure grade 3-4, pheochromocytoma, acute and chronic arterial insufficiency, hyperkalemia, shock of non-allergic origin (including cardiogenic, traumatic, hemorrhagic), cold injury, organic brain damage, closed-angle glaucoma; children and adolescents under 18 years of age (except for life-threatening conditions); pregnancy, breastfeeding period; simultaneous use of inhalational general anesthetics (halothane).

Epinephrine in combination with local anesthetics should not be used for local anesthesia of fingers and toes due to the risk of ischemic tissue damage.

In emergency conditions, all contraindications are relative.

With caution

Metabolic acidosis, coronary artery disease, arterial hypertension, hypercapnia, hypoxia, atrial fibrillation, ventricular arrhythmia, pulmonary hypertension, hypovolemia, myocardial infarction, occlusive vascular diseases (including history – arterial embolism, atherosclerosis, Buerger’s disease, diabetic endarteritis, Raynaud’s disease), diabetes mellitus, hyperthyroidism, long-standing bronchial asthma and emphysema, cerebral atherosclerosis, Parkinson’s disease, tetraplegia, convulsive syndrome, prostate hyperplasia and/or difficulty urinating; elderly age; paresis and paralysis, increased tendon reflexes in spinal cord injury.

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy and breastfeeding.

Pediatric Use

Contraindicated for use in children and adolescents under 18 years of age (except for life-threatening conditions).

Geriatric Use

Use with caution in elderly patients. A sharp increase in blood pressure when using epinephrine can lead to hemorrhage, especially in elderly patients with cardiovascular diseases.

Special Precautions

During treatment, it is recommended to determine serum potassium ion concentration, measure blood pressure, diuresis, cardiac output, ECG, central venous pressure, pulmonary artery pressure and pulmonary capillary wedge pressure.

Excessive doses of epinephrine in myocardial infarction can increase ischemia by increasing myocardial oxygen demand.

Epinephrine increases blood plasma glucose levels, therefore, in diabetes mellitus, higher doses of insulin and sulfonylurea derivatives are required.

Epinephrine is not advisable to use for a long time (constriction of peripheral vessels, leading to the possible development of necrosis or gangrene).

The use of epinephrine to correct arterial hypotension during childbirth is not recommended, as it may delay the second stage of labor; when administered in large doses to weaken uterine contraction, it can cause prolonged uterine atony with bleeding. When discontinuing treatment, doses should be reduced gradually, because sudden withdrawal of therapy can lead to severe arterial hypotension.

A sharp increase in blood pressure when using epinephrine can lead to hemorrhage, especially in elderly patients with cardiovascular diseases.

In patients with Parkinson’s disease, psychomotor agitation or temporary worsening of disease symptoms may be observed when using epinephrine, therefore caution should be exercised when using epinephrine in this category of persons.

Do not inject repeatedly into the same areas to avoid the development of tissue necrosis.

Injection of epinephrine into the gluteal muscles is not recommended.

Drug Interactions

Antagonists of epinephrine are alpha- and beta-adrenergic receptor blockers.

Non-selective beta-blockers potentiate the pressor effect of epinephrine.

When used simultaneously with cardiac glycosides, quinidine, tricyclic antidepressants, dopamine, inhalational anesthetics (chloroform, enflurane, halothane, isoflurane, methoxyflurane), cocaine, the risk of developing arrhythmias increases (simultaneous use is not recommended, except in cases of extreme necessity); with other sympathomimetic agents – increased severity of side effects from the cardiovascular system; with antihypertensive agents (including diuretics) – reduction of their effectiveness; with ergot alkaloids – increased vasoconstrictor effect (up to severe ischemia and development of gangrene).

Epinephrine reduces the effects of hypoglycemic agents (including insulin), antipsychotics, cholinomimetics, muscle relaxants, opioid analgesics, hypnotics.

The effectiveness of epinephrine is reduced in patients with severe anaphylactic reactions taking beta-blockers. In this case, salbutamol is administered intravenously.

Simultaneous use of epinephrine with MAO inhibitors (procarbazine, selegiline, as well as furazolidone) can cause sudden and significant increase in blood pressure, hyperpyretic crisis, headache, arrhythmias, vomiting; with nitrates – weakening of their therapeutic effect. With phenoxybenzamine – increased antihypertensive effect and tachycardia; with phenytoin – sudden decrease in blood pressure and bradycardia (depends on the dose and rate of administration); with thyroid hormone preparations – mutual enhancement of action.

Prolongation of the QT interval is possible with simultaneous use of epinephrine with the following drugs: with antiarrhythmic drugs (such as lidocaine, amiodarone, sotalol), with antibiotics (such as erythromycin, levofloxacin), with antihistamines (such as loratadine, diphenhydramine), with tricyclic and tetracyclic antidepressants (such as amitriptyline, imipramine, sertraline, chlorpromazine), with antipsychotics (such as haloperidol, risperidone), with dopamine receptor antagonists (such as domperidone), with antimalarial drugs (such as chloroquine, mefloquine), with antifungal drugs (such as ketoconazole, fluconazole), with antihypertensive drugs (such as indapamide, ephedrine), may cause QT interval prolongation.

Simultaneous use of epinephrine with diatrizates, iogulamic or ioxaglic acids – increased neurological effects, with ergot alkaloids may cause increased vasoconstrictor effect (up to severe ischemia and development of gangrene).

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.