Adrenaline (Solution) Instructions for Use

ATC Code

C01CA24 (Epinephrine)

Active Substance

Epinephrine (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Alpha-, beta-adrenergic agonist

Pharmacotherapeutic Group

Drugs for the treatment of heart diseases. Cardiotonic drugs other than cardiac glycosides. Adrenergic and dopaminergic drugs

Pharmacological Action

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

Under the action of epinephrine (adrenaline), due to stimulation of alpha-adrenergic receptors, the intracellular calcium content in smooth muscles increases. Activation of alpha₁-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 depot. 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 is the trigger for the development of responses from various target organs. As a result of stimulation of beta₁-adrenergic receptors in heart tissues, intracellular calcium increases. When beta₂-adrenergic receptors are stimulated, the 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 depot.

It has a pronounced effect on the cardiovascular system. It increases the heart rate and strength of heart contractions, stroke volume and cardiac output. Improves AV conduction, increases automaticity. Increases myocardial oxygen demand. Causes vasoconstriction of the 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 the heart rate.

Epinephrine relaxes the smooth muscles of the bronchi, reduces the tone and motility of the gastrointestinal tract, dilates the pupils, and helps reduce intraocular pressure. It causes hyperglycemia and increases the content of free fatty acids in plasma.

Pharmacokinetics

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

It crosses the placental barrier, does not cross the blood-brain barrier.

It is excreted in breast milk.

Indications

Immediate-type allergic reactions (including urticaria, angioneurotic edema, anaphylactic shock) developing from the use of medications, serums, blood transfusions, consumption of food products, insect bites, or the introduction 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 that does not respond to adequate volumes of replacement fluids (including shock, trauma, bacteremia, open-heart surgery, renal failure, chronic heart failure, drug overdose).

The 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 subcutaneously, intramuscularly, or as a slow intravenous infusion. Adjust the dose and route individually based on the clinical indication and patient status.

For anaphylactic shock, administer 0.3-0.5 mg (0.3-0.5 mL of a 1 mg/mL solution) intramuscularly into the anterolateral thigh. Repeat every 5-15 minutes if hemodynamic response is inadequate. For severe refractory shock, administer a slow intravenous infusion of 1-4 mcg/minute, titrating to effect.

For severe bronchospasm or asthma attack unresponsive to inhaled bronchodilators, administer 0.3-0.5 mg subcutaneously or intramuscularly. Doses may be repeated every 20 minutes to 4 hours as needed.

In cardiac arrest due to asystole or pulseless electrical activity, administer 1 mg (10 mL of a 0.1 mg/mL solution) intravenously. Repeat every 3-5 minutes during resuscitation. Follow current Advanced Cardiac Life Support (ACLS) protocols.

For symptomatic bradycardia or syncope in Morgagni-Adams-Stokes syndrome, initiate an intravenous infusion at 2-10 mcg/minute, titrating to achieve an adequate heart rate.

For hypoglycemia unresponsive to oral carbohydrates, administer 0.3 mg intramuscularly or subcutaneously.

To prolong the action of local anesthetics, add a concentration of 1:200,000 to 1:100,000 (5-10 mcg/mL) to the anesthetic solution. Avoid use in areas with end-arterial circulation (e.g., fingers, toes, ears, penis).

For topical hemostasis of superficial bleeding, apply a tampon or gauze saturated with a 1:1,000 solution directly to the bleeding site.

Continuously monitor heart rate, blood pressure, and electrocardiogram (ECG) during intravenous administration. Avoid rapid intravenous bolus injection, which can cause a precipitous hypertensive crisis or cerebral hemorrhage.

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 angioneurotic edema, 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 prostatic 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 of 3-4 degree, 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 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, prostatic 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, cardiac output, ECG, central venous pressure, pulmonary artery pressure and pulmonary capillary wedge pressure.

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

Epinephrine increases blood 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 inject repeatedly into the same areas to avoid the development of tissue necrosis.

It is not recommended to administer epinephrine into the gluteal muscles.

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, 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 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.