Adrenalin ^® is available as a single-use 1 mL vial and a multiple-use 30 mL vial for intramuscular and subcutaneous use.

Emergency treatment of allergic reactions (Type I), including anaphylaxis, which may result from allergic reactions to insect stings, biting insects, foods, drugs, sera, diagnostic testing substances and other allergens, as well as idiopathic anaphylaxis or exercise-induced anaphylaxis. The signs and symptoms associated with anaphylaxis include flushing, apprehension, syncope, tachycardia, thready or unobtainable pulse associated with hypotension, convulsions, vomiting, diarrhea and abdominal cramps, involuntary voiding, airway swelling, laryngospasm, bronchospasm, pruritus, urticaria or angioedema, swelling of the eyelids, lips, and tongue.

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 5/8 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, with repeat doses titrated to effect. Do not administer repeated injections at the same site, as the resulting vasoconstriction may cause tissue necrosis.

Inspect visually for particulate matter and discoloration prior to administration. Do not use if the solution is colored or cloudy, or if it contains particulate matter.

Adults and Children 30 kg (66 lbs) or more: 0.3 to 0.5 mg (0.3 mL 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.

Adrenalin ^® 1 mg/mL epinephrine injection, 1 mL solution in a single-use clear glass vial and 30 mL solution in a multiple-dose amber glass vial.

None.

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 (5.3) ].

Due to the lack of randomized, controlled clinical trials of epinephrine for the treatment of anaphylaxis, 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.

Angina may occur in patients with coronary artery disease [ see Warnings and Precautions (5.3) ].

Arrhythmias, including fatal ventricular fibrillation, have occurred, particularly in patients with underlying organic heart disease or patients receiving drugs that sensitize the heart to arrhythmias [ see  Warnings and Precautions (5.3) ].

Rapid rises in blood pressure associated with epinephrine use have produced cerebral hemorrhage, particularly in elderly patients with cardiovascular disease [ see Warnings and Precautions (5.3) ].

Respiratory: respiratory difficulties.

Neurological: dizziness , disorientation , excitability , headache , impaired memory , lightheadedness , nervousness , panic, psychomotor agitation, sleepiness , tingling , tremor, and weakness.

Psychiatric: anxiety, apprehensiveness, restlessness.

Gastrointestinal: nausea, vomiting.

Other:

Patients with Parkinson's disease may experience psychomotor agitation or a temporary worsening of symptoms [ see Warnings and Precautions (5.3) ].

Diabetic patients may experience transient increases in blood sugar [ see Warnings and Precautions (5.3) ].

Accidental injection into the digits, hands or feet may result in loss of blood flow to the affected area [ see Warnings and Precautions (5.1) ]. Adverse events experienced as a result of an injection into these areas include increased heart rate, local reactions including injection site pallor, coldness, hypoesthesia, and tissue loss, or injury at the injection site resulting in bruising, bleeding, discoloration, erythema, and skeletal injury.

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) ] .

Skin: sweating.

To report SUSPECTED ADVERSE REACTIONS, contact Par Pharmaceutical at 1-800-828-9393 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Epinephrine should be administered cautiously to patients taking other sympathomimetic agents because of the possibility of additive effects.

Patients who are concomitantly receiving cardiac glycosides, digitalis, diuretics, quinidine, and other antiarrhythmics should be observed carefully for the development of cardiac arrhythmias [ see  Warnings and Precautions (5.3) and Adverse Reactions (6) ].

Administer epinephrine cautiously to patients receiving halogenated hydrocarbon general anesthetics, such as halothane, as coadministration may result in arrhythmias.

The effects of epinephrine may be potentiated by tricyclic antidepressants such as imipramine, monoamine oxidase inhibitors (MAOI), levothyroxine sodium, and certain antihistamines, notably diphenhydramine, tripelannamine, and dexchlorpheniramine.

The cardiostimulating and bronchodilating effects of epinephrine are antagonized by beta-adrenergic blocking drugs, such as propranolol.

The vasoconstricting and hypertensive effects of epinephrine are antagonized by alpha-adrenergic blocking drugs, such as phentolamine.

Ergot alkaloids may reverse the pressor effects of epinephrine.

Epinephrine should not be used to counteract circulatory collapse or hypotension caused by phenothiazines, as a reversal of the pressor effects of epinephrine may result in further lowering of blood pressure.

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. Treatment consists of a rapidly acting α-adrenergic blocking drug and respiratory support.

Epinephrine is rapidly inactivated in the body and treatment following overdose with epinephrine is primarily supportive. 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.

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. Treatment of arrhythmias consists of administration of a beta-adrenergic blocking drug such as propranolol.

Overdosage sometimes results in extreme pallor and coldness of the skin, metabolic acidosis due to elevated blood lactic acid levels, and kidney failure. Suitable corrective measures must be taken in such situations.

Myocardial ischemia, myocardial infarction and cardiomyopathy have been noted in the literature following overdose of epinephrine.

Adrenalin ^® (epinephrine injection, USP) is a clear, colorless, sterile solution containing 1 mg/mL epinephrine, packaged as 1 mL of solution in a single-use 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, 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, 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:

Chemical Structure

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.

Adrenalin ^® 1 mL Single-Use Vials:

Each carton contains 25 single-use vials containing 1 mL Adrenalin ^® (epinephrine injection, USP) solution 1 mg/mL in a 3 mL clear glass vial.

NDC 42023-159-25      1 mL vial

Adrenalin ^® 30 mL Multi-Dose Vials:

Each carton contains 1 multiple-dose vial containing 30 mL Adrenalin ^® (epinephrine injection, USP) solution 1 mg/mL in a 36 mL amber glass vial.

NDC 42023-168-01      30 mL vial

Advise patients or their caregivers about common adverse reactions associated with the use of epinephrine including an increase in heart rate, the sensation of a more forceful heartbeat, palpitations, sweating, nausea and vomiting, difficulty breathing, pallor, dizziness, weakness or shakiness, headache, apprehension, nervousness, or anxiety. These symptoms and signs usually subside rapidly, especially with rest, quiet and recumbent positioning.

Warn patients with a good response to initial treatment about the possibility of recurrence of symptoms and instruct patients to obtain proper medical attention if symptoms return.

Warn patients with diabetes that they may develop increased blood glucose levels following epinephrine administration.

Rare cases of serious skin and soft tissue infections, including necrotizing fasciitis and myonecrosis caused by Clostridia (gas gangrene), have been reported at the injection site following epinephrine injection for anaphylaxis. Advise patients to seek medical care if they develop signs or symptoms of infection, such as persistent redness, warmth, swelling, or tenderness, at the epinephrine injection site [see Warnings and Precautions (5.2) ].