EpiPen Side Effects
Generic Name: epinephrine
Note: This page contains information about the side effects of epinephrine. Some of the dosage forms included on this document may not apply to the brand name EpiPen.
Not all side effects for EpiPen may be reported. You should always consult a doctor or healthcare professional for medical advice. Side effects can be reported to the FDA here.
For the Consumer
Applies to epinephrine: injection injectable, injection solution
In addition to its needed effects, some unwanted effects may be caused by epinephrine (the active ingredient contained in EpiPen). In the event that any of these side effects do occur, they may require medical attention.
You should check with your doctor immediately if any of these side effects occur when taking epinephrine:Incidence not known
- Abnormal or decreased touch sensation
- 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
- fast, irregular, pounding, or racing heartbeat or pulse
- fear or nervousness
- nausea or vomiting
- paleness of the skin
- pounding in the ears
- shakiness in the legs, arms, hands, or feet
- slow or fast heartbeat
- trembling or shaking of the hands or feet
- troubled breathing
- unusual tiredness or weakness
If any of the following symptoms of overdose occur while taking epinephrine, get emergency help immediately:Symptoms of overdose
- coldness of the skin
- decreased urine output
- lightheadedness, dizziness, or fainting
- muscle twitching
- pounding, slow heartbeat
- rapid weight gain
- rapid, deep breathing
- stomach cramps
- swelling of the face, ankles, or hands
For Healthcare Professionals
Applies to epinephrine: compounding powder, inhalation aerosol, inhalation solution, injectable kit, injectable solution, intravenous solution, subcutaneous suspension
Nervous system side effects have included fear, agitation, anxiety, tenseness, restlessness, headache, tremor, dizziness, lightheadedness, nervousness, sleeplessness, excitability, weakness, and increased parkinsonian tremors. Complications associated with epidural anesthesia with epinephrine (the active ingredient contained in EpiPen) have included nerve root ischemia and clinical paralysis/plegia.
Cardiovascular side effects have included elevations in heart rate or blood pressure in up to 55% and arrhythmias in 3% to 17% (including fatal ventricular arrhythmias) when used to treat cardiac arrest. In smaller doses, epinephrine (the active ingredient contained in EpiPen) has caused peripheral coronary arterial vasodilation, but in larger doses, epinephrine has caused diffuse vasoconstriction. This has caused increased peripheral vascular resistance, which was important in patients with coronary artery disease (worsened myocardial ischemia/angina) or hypertension (risk of emergent hypertension/stroke). Dilated cardiomyopathy and acute left ventricular dysfunction have been associated with the use of epinephrine.
Arrhythmias, including fatal ventricular fibrillation, have been reported in patients with underlying cardiac disease. Rapid rises in blood pressure have produced cerebral hemorrhage, particularly in elderly patients with cardiovascular disease. Angina may occur in patients with coronary artery disease.
Epinephrine can induce hypokalemia with resultant T wave changes on the electrocardiogram.
Rare cases of myocardial infarction have been associated with relatively small doses of epinephrine in patients at risk for coronary artery disease.
Rare cases of cardiomyopathy have been associated with brief and chronic exposure to epinephrine (including inhaled epinephrine). Animal studies have shown that catecholamines can cause an influx of calcium into myocardial cells, which may cause myocardial injury, particularly during periods of epinephrine-induced coronary vasoconstriction. Limited animal data suggest that calcium antagonists may protect against the cardiotoxic effects of catecholamines by preventing the generation of plasma borne cytotoxic compounds, which are probably free radicals.
Epinephrine may be more arrhythmogenic in some patients, such as patients with congenital long QT syndrome.
Local side effects have included local tissue ischemia after repeated injections. Chronic IM epinephrine (the active ingredient contained in EpiPen) injections have induced local vasoconstriction, predisposing patients to Clostridial infections. Other local reactions have included injection site pallor, coldness and hypoesthesia or injury at the injection site resulting in bruising, bleeding, discoloration, erythema or skeletal injury.
Psychiatric side effects have included agitation, disorientation, impaired memory, aggressive or assaultive behavior, hallucinations, and psychosis.
Respiratory side effects have rarely included pulmonary edema. In some cases, acute left ventricular dysfunction has been documented in the presence of epinephrine-induced pulmonary edema. In some patients, epinephrine (the active ingredient contained in EpiPen) has precipitated severe, prolonged asthmatic attacks.
Metabolic side effects have included severe metabolic acidosis because of elevated blood concentrations of lactic acid after prolonged use of intravenous epinephrine (the active ingredient contained in EpiPen) Catecholamines have induced glycogenolysis, elevated blood glucose and insulin concentrations, and hypokalemia. Rare cases of hyperglycemia and acidosis have been associated with high catecholamine states, such as anaphylaxis.
Mattana and Singhal reviewed 420 consecutive cases of cardiac arrest and found a 28.6% incidence of acute renal failure (ARF) among patients who survived for at least 24 hours after cardiac arrest. Patients in whom ARF developed received markedly higher doses of epinephrine (the active ingredient contained in EpiPen) during resuscitative efforts than patients without ARF. High doses of epinephrine were associated with a longer duration of cardiopulmonary resuscitation. The patients with ARF had a significantly decreased survival rate. It is possible that patients with severe cardiac disease were less resuscitatable, required more epinephrine, and were prone to develop ARF anyway. Other data have failed to associated ARF with the use of high dose epinephrine.
Renal side effects have included new or worsened renal insufficiency in adult survivors of cardiac arrest, adults who underwent epinephrine-assisted venography, and in rare pediatric cases.
Hypersensitivity side effects have been extremely unusual. Contact dermatitis has been associated with ocularly applied epinephrine (the active ingredient contained in EpiPen) These reactions have typically presented with lid edema and a thick yellow discharge.
Gastrointestinal side effects have included nausea and vomiting.
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