Side Effects of EpiPen (auto-injectable epinephrine)

EpiPen (auto-injectable epinephrine) is a sympathomimetic catecholamine used for self-administration during life-threatening allergic reactions, including

• anaphylactic reactions caused by insect stings or bites,
• allergen immunotherapy,
• foods,
• drugs,
• chemicals used for diagnostic testing substances such as radiocontrast media, and
• other allergens.

EpiPen also is used for treating anaphylaxis due to exercise or unknown causes. EpiPen is used for emergency use only and are should not replace proper medical care. Epinephrine, the medicine contained in EpiPen, is an excitatory chemical naturally made by our bodies.

Epinephrine stimulates alpha and beta-adrenergic receptors found throughout the body. When injected during an allergic reaction, epinephrine works in multiple ways to treat the many signs of anaphylaxis. It causes blood vessels to constrict or tighten which helps to increase blood pressure and decrease swelling.

Epinephrine also stimulates the heart muscle, causing the heart to beat faster and pump more blood to the vital organs. Epinephrine helps patients breathe better by relaxing the muscles in the lungs and allowing the airways to open up. Additionally, it also helps to prevent further release of inflammatory chemicals that were triggered by the initial allergic reaction.

Common side effects of EpiPen include

• anxiety,
• dizziness,
• shortness of breath,
• flushing,
• headache,
• nausea,
• nervousness,
• pale skin (pallor),
• restlessness,
• sweating,
• tremor, and
• vomiting.

Serious side effects of EpiPen include

• abnormal heartbeats,
• chest pain,
• high blood pressure,
• respiratory difficulties,
• increased heart rate, and
• palpitations.

Drug interactions of EpiPen include cardiac glycosides, diuretics (water pills), or drugs for treating irregular heartbeats (anti-arrhythmics), because coadministration can cause the development of irregular heartbeats.

• The effects of EpiPen may be enhanced by medicines such as tricyclic antidepressants, monoamine oxidase inhibitors (MAOIs), levothyroxine, and certain antihistamines.
• The treatment benefits of EpiPen can be reduced by beta-adrenergic blocking medicines such as propranolol and alpha-adrenergic blocking medicines such as phentolamine.
• Some anti-migraine medications may also interfere with the benefits of EpiPen treatment.

Use of EpiPen has not been adequately evaluated in pregnant women. EpiPen should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

It is unknown if EpiPen is excreted in breast milk. Since many drugs are excreted in breast milk and have the potential of causing harm to the nursing infant, caution should be used when EpiPen is administered to a breastfeeding mother.

Common side effects of EpiPen include:

• Anxiety
• Dizziness
• Shortness of breath
• Flushing
• Headache
• Nausea
• Nervousness
• Pale skin (pallor)
• Restlessness
• Sweating
• Tremor
• Vomiting

Possible serious side effects of EpiPen include:

• Abnormal heart beats
• Chest pain
• High blood pressure
• Respiratory difficulties
• Increased heart rate
• Palpitations

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.

Common adverse reactions to systemically administered epinephrine include

• anxiety;
• apprehensiveness;
• restlessness;
• tremor;
• weakness;
• dizziness;
• sweating;
• palpitations;
• pallor;
•  nausea and vomiting;
• headache; and/or respiratory difficulties.

These symptoms occur in some persons receiving therapeutic doses of epinephrine, but are more likely to occur in patients with hypertension or hyperthyroidism.

• Arrhythmias, including fatal ventricular fibrillation, have been reported, particularly in patients with underlying cardiac disease or those receiving certain drugs.
• 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.
• Rare cases of stress cardiomyopathy have been reported in patients treated with epinephrine.
• Accidental injection into the digits, hands or feet may result in loss of blood flow to the affected area.
• Adverse events experienced as a result of accidental injections may include increased heart rate, local reactions including injection site pallor, coldness and hypoesthesia or injury at the injection site resulting in bruising, bleeding, discoloration, erythema or skeletal injury.
• Lacerations, bent needles, and embedded needles have been reported when EpiPen has been injected into the thigh of young children who are uncooperative and kick or move during the injection.
• Injection into the buttock has resulted in cases of gas gangrene.
• 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, including EpiPen, in the thigh.

• Patients who receive epinephrine while concomitantly taking cardiac glycosides, diuretics, or anti-arrhythmics should be observed carefully for the development of cardiac arrhythmias.
• The effects of epinephrine may be potentiated by tricyclic antidepressants, monoamine oxidase inhibitors, levothyroxine sodium, and certain antihistamines, notably chlorpheniramine, tripelennamine, and diphenhydramine.
• 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 alphaadrenergic blocking drugs, such as phentolamine.
• Ergot alkaloids may also reverse the pressor effects of epinephrine.