Epineprine

FDA Drug Information • Also known as: Adrenalin

Brand Names: Adrenalin
Drug Class: alpha-Adrenergic Agonist [EPC], beta-Adrenergic Agonist [EPC], Catecholamine [EPC]
Route: INTRAMUSCULAR, INTRAVENOUS, SUBCUTANEOUS
Dosage Form: INJECTION
Product Type: HUMAN PRESCRIPTION DRUG

Description

11 DESCRIPTION Adrenalin (epinephrine injection, USP) is a clear, colorless, sterile solution containing 1 mg/mL epinephrine, packaged as 1 mL of solution in a single dose clear glass vial or 30 mL of solution in a multiple dose amber glass vial. In the 1 mL vial, each 1 mL of Adrenalin solution contains 1 mg epinephrine, 7.3 mg sodium chloride, 0.457 mg sodium metabisulfite, 1 mg sodium hydroxide, 2.25 mg tartaric acid, 0.20 mg disodium edetate dihydrate, 5.32 mg of 4% hydrochloric acid to adjust pH, and water for injection. In the 30 mL vial, each 1 mL of Adrenalin solution contains 1 mg epinephrine, 6.15 mg sodium chloride, 0.457 mg sodium metabisulfite, 0.920 mg sodium hydroxide, 2.25 mg tartaric acid, 0.20 mg disodium edetate dihydrate, 5.18 mg of 4% hydrochloric acid to adjust pH, 5.25 mg chlorobutanol as a preservative and water for injection. The pH range is 2.2-5.0. Epinephrine is a sympathomimetic catecholamine. The chemical name of epinephrine is: 1,2-Benzenediol, 4-[(1R)-1-hydroxy-2-(methylamino)ethyl]-, or (-)-3,4-Dihydroxy-α-[2-(methylamino)ethyl]benzyl alcohol. The chemical structure of epinephrine is: The molecular weight of epinephrine is 183.2. Epinephrine solution deteriorates rapidly on exposure to air or light, turning pink from oxidation to adrenochrome and brown from the formation of melanin. Fromula1.jpg

What Is Epineprine Used For?

1 INDICATIONS AND USAGE 1.1 Anaphylaxis Emergency treatment of allergic reactions (Type I), including anaphylaxis, which may result from insect stings or bites, foods, drugs, sera, diagnostic testing substances and other allergens, as well as idiopathic anaphylaxis or exercise-induced anaphylaxis. 1.2 Hypotension associated with Septic Shock Adrenalin is indicated to increase mean arterial blood pressure in adult patients with hypotension associated with septic shock. Adrenalin® is a non-selective alpha and beta adrenergic agonist indicated for: Emergency treatment of allergic reactions (Type 1), including anaphylaxis (1.1) To increase mean arterial blood pressure in adult patients with hypotension associated with septic shock (1.2)

Dosage and Administration

2 DOSAGE AND ADMINISTRATION 2.1 General Considerations Inspect visually for particulate matter and discoloration prior to administration; solution should be clear and colorless. Do not use if the solution is colored or cloudy, or if it contains particulate matter. 2.2 Anaphylaxis Inject Adrenalin intramuscularly or subcutaneously into the anterolateral aspect of the thigh, through clothing if necessary. When administering to a child, to minimize the risk of injection related injury, hold the leg firmly in place and limit movement prior to and during an injection. The injection may be repeated every 5 to 10 minutes as necessary. For intramuscular administration, use a needle long enough (at least 1/2 inch) to ensure the injection is administered into the muscle. Monitor the patient clinically for the severity of the allergic reaction and potential cardiac effects of the drug, and repeat as needed. Do not administer repeated injections at the same site, as the resulting vasoconstriction may cause tissue necrosis. Adults and Children 30 kg (66 lbs) or more: 0.3 to 0.5 mg (0.3 to 0.5 mL) of undiluted Adrenalin administered intramuscularly or subcutaneously in the anterolateral aspect of the thigh, up to a maximum of 0.5 mg (0.5 mL) per injection, repeated every 5 to 10 minutes as necessary. Monitor clinically for reaction severity and cardiac effects. Children less than 30 kg (66 lbs): 0.01 mg/kg (0.01 mL/kg) of undiluted Adrenalin administered intramuscularly or subcutaneously in the anterolateral aspect of the thigh, up to a maximum of 0.3 mg (0.3 mL) per injection, repeated every 5 to 10 minutes as necessary. Monitor clinically for reaction severity and cardiac effects. 2.3 Hypotension associated with Septic Shock Dilute 1 mL (1 mg) of epinephrine from its vial to 1,000 mL of a 5 percent dextrose or 5 percent dextrose and sodium chloride solution to produce a 1 mcg per mL dilution. Administration in saline solution alone is not recommended. If indicated, administer whole blood or plasma separately. Whenever possible, give infusions of epinephrine into a large vein. Avoid using a catheter tie-in technique, because the obstruction to blood flow around the tubing may cause stasis and increased local concentration of the drug. Avoid the veins of the leg in elderly patients or in those suffering from occlusive vascular diseases. To provide hemodynamic support in septic shock associated hypotension in adult patients, the suggested dosing infusion rate of intravenously administered epinephrine is 0.05 to 2 mcg/kg/min, and is titrated to achieve a desired mean arterial pressure (MAP). The dosage may be adjusted periodically, such as every 10 to 15 minutes, in increments of 0.05 to 0.2 mcg/kg/min, to achieve the desired blood pressure goal. After hemodynamic stabilization, wean incrementally over time, such as by decreasing doses of epinephrine every 10 minutes to determine if the patient can tolerate gradual withdrawal. Adrenalin diluted in 5 percent...

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS Common adverse reactions to systemically administered epinephrine include anxiety, apprehensiveness, restlessness, tremor, weakness, dizziness, sweating, palpitations, pallor, nausea and vomiting, headache, and respiratory difficulties. These symptoms occur in some persons receiving therapeutic doses of epinephrine, but are more likely to occur in patients with heart disease, hypertension, or hyperthyroidism [see Warnings and Precautions (5.7)]. The true incidence of adverse reactions associated with the systemic use of epinephrine is difficult to determine. Adverse reactions reported in observational trials, case reports, and studies are listed below by body system: Cardiovascular: angina, arrhythmias, hypertension, pallor, palpitations, tachyarrhythmia, tachycardia, vasoconstriction, ventricular ectopy and stress cardiomyopathy. Rapid rises in blood pressure associated with epinephrine use have produced cerebral hemorrhage, particularly in elderly patients with cardiovascular disease [see Warnings and Precautions (5.7)]. Neurological: disorientation, impaired memory, panic, psychomotor agitation, sleepiness, tingling. Psychiatric: anxiety, apprehensiveness, restlessness. Other: Patients with Parkinson’s disease may experience psychomotor agitation or a temporary worsening of symptoms [see Warnings and Precautions (5.7)]. Diabetic patients may experience transient increases in blood sugar. Injection into the buttock has resulted in cases of gas gangrene [see Warnings and Precautions (5.1)]. Rare cases of serious skin and soft tissue infections, including necrotizing fasciitis and myonecrosis caused by Clostridia (gas gangrene), have been reported following epinephrine injection in the thigh [see Warnings and Precautions (5.2)]. Common adverse reactions to systemically administered epinephrine include anxiety, tremor, weakness, dizziness, sweating, palpitations and pallor (6) To report SUSPECTED ADVERSE REACTIONS, contact Endo at 1-800-828-9393 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Drug Interactions

7 DRUG INTERACTIONS 7.1 Drugs Antagonizing Pressor Effects of Epinephrine α-blockers, such as phentolamine Vasodilators, such as nitrates Diuretics Antihypertensives Ergot alkaloids Phenothiazine antipsychotics 7.2 Drugs Potentiating Pressor Effects of Epinephrine Sympathomimetics β-blockers, such as propranolol Tricyclic anti-depressants Monoamine oxidase (MAO) inhibitors Catechol-O-methyl transferase (COMT) inhibitors, such as entacapone Clonidine Doxapram Oxytocin 7.3 Drugs Potentiating Arrhythmogenic Effects of Epinephrine Cardiac arrhythmias are more common among patients receiving any of the following drugs [see Warnings and Precautions (5.7) and Adverse Reactions (6)]. β-blockers, such as propranolol Cyclopropane or halogenated hydrocarbon anesthetics, such as halothane Antihistamines Thyroid hormones Diuretics Cardiac glycosides, such as digitalis glycosides Quinidine 7.4 Drugs Potentiating Hypokalemic Effects of Epinephrine Potassium depleting diuretics Corticosteroids Theophylline Drugs that counter the pressor effects of epinephrine include alpha blockers, vasodilators such as nitrates, diuretics, antihypertensives and ergot alkaloids. (7.1) Drugs that potentiate the effects of epinephrine include sympathomimetics, beta blockers, tricyclic antidepressants, MAO inhibitors, COMT inhibitors, clonidine, doxapram, oxytocin, levothyroxine sodium, quinidine and certain antihistamines. (7.2) Drugs that increase the arrhythmogenic potential of epinephrine include beta blockers, cyclopropane and halogenated hydrocarbon anesthetics, antihistamines, exogenous thyroid hormones, diuretics, and cardiac glycosides. Observe for development of cardiac arrhythmias. (7.3) Potassium-depleting drugs, including corticosteroids, diuretics, and theophylline, potentiate the hypokalemic effects of epinephrine. (7.4)

Contraindications

4 CONTRAINDICATIONS None. None (4)

Overdosage

10 OVERDOSAGE Overdosage of epinephrine may produce extremely elevated arterial pressure, which may result in cerebrovascular hemorrhage, particularly in elderly patients. Overdosage may also result in pulmonary edema because of peripheral vascular constriction together with cardiac stimulation. Epinephrine overdosage can also cause transient bradycardia followed by tachycardia and these may be accompanied by potentially fatal cardiac arrhythmias. Premature ventricular contractions may appear within one minute after injection and may be followed by multifocal ventricular tachycardia (prefibrillation rhythm). Subsidence of the ventricular effects may be followed by atrial tachycardia and occasionally by atrioventricular block. Myocardial ischemia and infarction, cardiomyopathy, extreme pallor and coldness of the skin, metabolic acidosis due to elevated blood lactic acid levels, and renal insufficiency have also been reported. Epinephrine is rapidly inactivated in the body and treatment following overdose with epinephrine is primarily supportive. Treatment of pulmonary edema consists of a rapidly acting alpha-adrenergic blocking drug (such as phentolamine mesylate) and respiratory support. Treatment of arrhythmias consists of administration of a beta-adrenergic blocking drug (such as propranolol). If necessary, pressor effects may be counteracted by rapidly acting vasodilators or α-adrenergic blocking drugs. If prolonged hypotension follows such measures, it may be necessary to administer another pressor drug.

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING Adrenalin 1 mg/mL Single Dose Vials: Each carton contains 25 single dose vials containing 1 mg/mL Adrenalin (epinephrine injection, USP) solution in a 3 mL clear glass vial. NDC 42023-159-01 1 mL Single Dose Vial NDC 42023-159-25 25 Single Dose Vials x 1 mL each Discard unused portion. Adrenalin 30 mg/30 mL (1 mg/mL) Multiple Dose Vials: Each carton contains 1 multiple dose vial containing 30 mg/30 mL (1 mg/mL) Adrenalin (epinephrine injection, USP) solution in a 36 mL amber glass vial. NDC 42023-168-01 30 mL Multiple Dose Vial Vial and contents must be discarded 30 days after initial use. Store between 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature]. Epinephrine is light sensitive. Protect from light and freezing. Inspect visually for particulate matter and discoloration prior to administration. Do not use the solution if it is colored or cloudy, or if it contains particulate matter. Product repackaged by: Henry Schein, Inc., Bastian, VA 24314 From Original Manufacturer/Distributor's NDC and Unit of Sale To Henry Schein Repackaged Product NDC and Unit of Sale Total Strength/Total Volume (Concentration) per unit NDC 42023-159-25 25 Single Dose Vials x 1 mL each NDC 0404-9810-01 1 1 mL Single Dose Vial in a bag (Vial bears NDC 42023-159-01) 1 mg/mL

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.