Adrenalin

Adverse Reactions Associated With Intramuscular/Subcutaneous Use (For Anaphylaxis)

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].

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, and ventricular ectopy.

Angina may occur in patients with coronary artery disease [see WARNINGS AND PRECAUTIONS].

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].

Rapid rises in blood pressure associated with epinephrine use have produced cerebral hemorrhage, particularly in elderly patients with cardiovascular disease [see WARNINGS AND PRECAUTIONS].

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].

Diabetic patients may experience transient increases in blood sugar [see WARNINGS AND PRECAUTIONS].

Accidental injection into the digits, hands or feet may result in loss of blood flow to the affected area [see WARNINGS AND PRECAUTIONS]. 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].

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].

Skin: sweating.

Adverse Reactions Associated With Intraocular Use (For Mydriasis)

Epinephrine containing sodium bisulfite has been associated with corneal endothelial damage when used in the eye at undiluted concentrations (1 mg/mL).

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

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 betaadrenergic 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.

Mechanism Of Action

Epinephrine acts on both alpha and beta-adrenergic receptors.

Pharmacodynamics

Through its action on alpha-adrenergic receptors, epinephrine lessens the vasodilation and increased vascular permeability that occurs during anaphylaxis, which can lead to loss of intravascular fluid volume and hypotension.

Through its action on beta-adrenergic receptors, epinephrine causes bronchial smooth muscle relaxation and helps alleviate bronchospasm, wheezing and dyspnea that may occur during anaphylaxis.

Epinephrine also alleviates pruritus, urticaria, and angioedema and may relieve gastrointestinal and genitourinary symptoms associated with anaphylaxis because of its relaxer effects on the smooth muscle of the stomach, intestine, uterus and urinary bladder.

Epinephrine increases glycogenolysis, reduces glucose up take by tissues, and inhibits insulin release in the pancreas, resulting in hyperglycemia and increased blood lactic acid [see WARNINGS AND PRECAUTIONS].

Epinephrine causes mydriasis when administered intraocularly or parenterally.

Pharmacokinetics

When administered parenterally or intraocularly, epinephrine has a rapid onset and short duration of action.

The extent of human systemic exposure at the labeled intraocular dose has not been evaluated, however, significant systemic concentrations or plasma exposure of epinephrine are not expected when administered intraocularly.

Clinical Studies

Induction And Maintenance Of Mydriasis During Intraocular Surgery

In randomized, controlled studies, patients undergoing routine cataract extraction were evaluated after receiving intraocular irrigation with or without epinephrine diluted up to 1:1,666,666 (0.6 mcg/mL). Patients have also been evaluated after receiving bolus intracameral injections of epinephrine diluted between 1:25,000 (40 mcg/mL) and 1:400,000 (2.5 mcg/mL).

In patients with similar pupil diameters at baseline, with or without the use of preoperative mydriatic agents, mydriasis was maintained better in the eyes receiving epinephrine by an average of one to two millimeters in pupil diameter. Pupil constriction to 5mm or less occurred more often in the patients not receiving epinephrine.

Mean pulse rate and blood pressure showed no significant difference between patients receiving epinephrine and controls and there was no increased incidence of ventricular dysrhythmias in patients receiving epinephrine.

Seek emergency medical attention after any use of epinephrine to treat a severe allergic reaction. After the injection you will need to receive further treatment and observation.

Follow all directions on your prescription label. Do not use this medicine in larger or smaller amounts or for longer than recommended.

Epinephrine is injected into the muscle of your outer thigh. In an emergency, this injection can be given through your clothing.

Your medicine may also come with a "trainer pen." The trainer pen contains no medicine and no needle. It is only for non-emergency use to practice giving yourself an epinephrine injection. Do not use a trainer pen to treat an allergic reaction.

The auto-injector device is a disposable single-use system that comes with patient instructions for safe and effective use. Do not inject this medicine if you do not understand these instructions.

Do not remove the safety cap until you are ready to use the auto-injector. Never put your fingers over the injector tip when removing the safety cap or after the safety cap has been removed.

To use an epinephrine auto-injector:

• Form a fist around the auto-injector with the tip pointing down. Pull off the safety cap.

• Place the tip against the fleshy portion of your outer thigh. You may give the injection directly through your clothing.

• Push the auto-injector firmly against your thigh to release the needle that injects the dose of epinephrine. Hold the auto-injector in place for 10 seconds after activation.

• Remove the auto-injector from your thigh and massage the area gently. Carefully re-insert the used device needle-first into the carrying tube. Re-cap the tube and take it with you to the emergency room so that anyone who treats you will know how much epinephrine you have received.

• Use an auto-injector only one time. Do not try to reinsert an auto-injector a second time if the needle has come out of your skin before the full 10 seconds. If the needle is bent from the first use, it may cause serious injury to your skin.

Seek emergency medical attention after any use of epinephrine to treat a severe allergic reaction. The effects of epinephrine may wear off after 10 or 20 minutes. You will need to receive further treatment and observation.

Do not use epinephrine injection if it has changed colors or has particles in it, or if the expiration date on the label has passed. Call your pharmacist for a new prescription.

Store at room temperature away from moisture, heat, and light. Do not refrigerate or freeze this medication, and do not store it in a car.

Other drugs may interact with epinephrine injection, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell each of your health care providers about all medicines you use now and any medicine you start or stop using.

To make sure you can safely use epinephrine, tell your doctor if you have any of these other conditions:

• heart disease or high blood pressure;
• a heart rhythm disorder;
• coronary artery disease;
• Parkinson's disease;
• diabetes; or
• a thyroid disorder.

FDA pregnancy category C. It is not known whether epinephrine will harm an unborn baby. If possible before using this medicine, tell your doctor if you are pregnant.

Do not use epinephrine without your doctor's advice if you are breast-feeding a baby.

In an emergency situation, it may not be possible before you use epinephrine to tell your caregivers if you are pregnant or breast-feeding. Make sure any doctor caring for your pregnancy or your baby knows you have received this medication.

Since epinephrine is normally used only as needed in an emergency, you are not likely to be on a dosing schedule. Do not use repeat doses of epinephrine without a doctor's advice.

• Adrenaclick
• Benadryl

• Intal

© Adrenalin Patient Information is supplied by Cerner Multum, Inc. and Adrenalin Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

Applies to epinephrine: injection injectable, injection solution

Along with its needed effects, epinephrine (the active ingredient contained in Adrenalin) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking epinephrine:

• Abnormal or decreased touch sensation
• anxiety
• arm, back, or jaw pain
• bleeding, blistering, burning, coldness, discoloration of the skin, feeling of pressure, hives, infection, inflammation, itching, lumps, numbness, pain, rash, redness, scarring, soreness, stinging, swelling, tenderness, tingling, ulceration, or warmth at the injection site
• blurred vision
• chest pain or discomfort
• chest tightness or heaviness
• cold, pale, or bluish color of the skin of the fingers or toes
• dizziness
• fainting
• fast, slow, irregular, pounding, or racing heartbeat or pulse
• fear or nervousness
• headache
• nausea or vomiting
• numbness, tingling, or pain in the fingers
• paleness of the skin
• pounding in the ears
• restlessness
• shakiness in the legs, arms, hands, or feet
• stroke
• sweating
• trembling or shaking of the hands or feet
• troubled breathing
• unusual tiredness or weakness

Get emergency help immediately if any of the following symptoms of overdose occur while taking epinephrine:

• Agitation
• coldness of the skin
• coma
• confusion
• decreased awareness or responsiveness
• decreased urine output
• depression
• drowsiness
• hostility
• irritability
• lightheadedness, dizziness, fainting
• muscle twitching
• rapid weight gain
• rapid, deep breathing
• seizures
• severe sleepiness
• stomach cramps
• swelling of the face, ankles, or hands
• unusual drowsiness, dullness, tiredness, weakness, or feeling of sluggishness