Epinephrine (Solution) Instructions for Use

Marketing Authorization Holder

Mir Chemical and Pharmaceutical Concern, LLC (Russia)

Manufactured By

NPC Eskom, PJSC (Russia)

ATC Code

C01CA24 (Epinephrine)

Active Substance

Epinephrine (Rec.INN registered by WHO)

Dosage Form

Epinephrine

Solution for injection 1 mg/1 ml: amp. 1 ml 3, 5, 10 or 20 pcs.

Dosage Form, Packaging, and Composition

Solution for injection transparent, colorless or slightly colored.

Excipients: sodium chloride – 8 mg, sodium disulfite (sodium metabisulfite) – 1 mg, disodium edetate dihydrate – 0.3 mg, hydrochloric acid solution 1M – to adjust pH to 2.2-5.0, water for injection – up to 1 ml.

1 ml – ampoules (3) – contour cell packaging (1) – cardboard packs.
1 ml – ampoules (5) – contour cell packaging (1) – cardboard packs.
1 ml – ampoules (5) – contour cell packaging (2) – cardboard packs.
1 ml – ampoules (5) – contour cell packaging (4) – cardboard packs.
1 ml – ampoules (10) – contour cell packaging (1) – cardboard packs.
1 ml – ampoules (10) – contour cell packaging (2) – cardboard packs.
1 ml – ampoules (10) – cardboard packs.

Clinical-Pharmacological Group

Alpha-, beta-adrenergic agonist

Pharmacotherapeutic Group

Drugs for the treatment of heart diseases; cardiotonic agents, except cardiac glycosides; adrenergic and dopaminergic agents

Pharmacological Action

Adrenomimetic, has a direct stimulating effect on α- and β-adrenergic receptors.

Under the action of epinephrine (adrenaline), stimulation of α-adrenergic receptors leads to an increase in intracellular calcium content in smooth muscles. Activation of α₁-adrenergic receptors increases phospholipase C activity (via stimulation of G-protein) and the formation of inositol triphosphate and diacylglycerol. This promotes the release of calcium from the sarcoplasmic reticulum stores. Activation of α₂-adrenergic receptors leads to the opening of calcium channels and increased calcium entry into cells.

Stimulation of β-adrenergic receptors causes G-protein-mediated activation of adenylate cyclase and increased cAMP formation. This process is the trigger for the development of responses from various target organs. As a result of stimulation of β₁-adrenergic receptors in heart tissues, intracellular calcium increases. When β₂-adrenergic receptors are stimulated, free intracellular calcium in smooth muscles decreases, due on one hand to increased transport out of the cell, and on the other hand to 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 slowing of 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 the content of free fatty acids in plasma.

Pharmacokinetics

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

Penetrates the placental barrier, does not penetrate 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 transfusion, consumption of food products, insect bites or administration of 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).

Need 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).

For the purpose of stopping bleeding.

ICD codes

Dosage Regimen

Administer via subcutaneous, intramuscular, or slow intravenous infusion routes. Apply topically for hemostasis. Determine the dosage individually based on the clinical indication and patient status.

For anaphylactic shock, administer 0.3-0.5 mg (0.3-0.5 ml) intramuscularly or subcutaneously. Repeat the injection every 10-20 minutes if required. For severe cases, dilute 1 mg (1 ml) in 10 ml of 0.9% sodium chloride solution and administer 0.1 mg (1 ml of the dilution) by slow intravenous injection over several minutes.

For acute bronchospasm (asthma attack), use a dose of 0.3-0.5 mg (0.3-0.5 ml) subcutaneously. Doses may be repeated up to three times at 20-minute intervals if necessary.

For cardiac arrest (asystole), administer 1 mg (1 ml) intravenously. If intravenous access is not available, administer via the intraosseous route. Repeat doses every 3-5 minutes during resuscitation.

For severe hypotension or shock unresponsive to fluid replacement, initiate a continuous intravenous infusion. Dilute 1 mg in 250 ml of 5% dextrose or 0.9% sodium chloride (resulting concentration: 4 mcg/ml). Initiate infusion at a rate of 1 mcg/minute and titrate to effect, typically between 1-10 mcg/minute.

For prolongation of local anesthesia, add epinephrine to the local anesthetic solution at a final concentration of 1:200,000 or 1:100,000. Do not exceed a total dose of 0.3 mg per anesthesia procedure.

For topical hemostasis, apply a sterile gauze or tampon soaked in the solution directly to the bleeding site. Do not inject.

Monitor heart rate, blood pressure, and ECG continuously during intravenous administration. Adjust the infusion rate based on hemodynamic response. Avoid extravasation, as it may cause tissue necrosis.

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 conditions directly life-threatening); pregnancy, breastfeeding period; simultaneous use of inhalational agents for general anesthesia (halothane).

Epinephrine in combination with local anesthetics is not 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 in 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 conditions directly life-threatening).

Geriatric Use

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

Special Precautions

During treatment, it is recommended to determine the concentration of potassium ions in the blood serum, measure blood pressure, diuresis, minute blood flow volume, 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.

It is not advisable to use epinephrine 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 the development of 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 administer repeatedly into the same areas, to avoid the development of tissue necrosis.

Administration of epinephrine into the gluteal muscles is not recommended.

Drug Interactions

Antagonists of epinephrine are α- and β-adrenergic receptor blockers.

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

When used simultaneously with cardiac glycosides, quinidine, tricyclic antidepressants, dopamine, agents for inhalation anesthesia (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 β-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 pronounced increase in blood pressure, hyperpyretic crisis, headache, arrhythmias, vomiting; with nitrates – weakening of their therapeutic action. With phenoxybenzamine – increased antihypertensive action 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 – enhancement of 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.