What are the side effects of using an EpiPen (epinephrine)?

Side Effects of EpiPen (Epinephrine)

The most common side effects of EpiPen (epinephrine) include transient anxiety, fear, restlessness, tremor, weakness, dizziness, sweating, palpitations, pallor, nausea, vomiting, headache, and respiratory difficulties. 1

Common Side Effects

Epinephrine has a narrow therapeutic-to-toxic index (risk-to-benefit ratio). When administered at therapeutic doses, epinephrine commonly causes mild and transient adverse effects including:

• Cardiovascular effects:

  • Palpitations
  • Increased heart rate
  • Pallor

• Neurological effects:

  • Anxiety
  • Restlessness
  • Tremor
  • Dizziness
  • Headache

• Other effects:

  • Sweating
  • Nausea and vomiting
  • Weakness

These symptoms are expected physiological responses to epinephrine and typically resolve quickly as the medication is metabolized. They occur due to epinephrine's stimulation of alpha and beta-adrenergic receptors throughout the body 2, 1.

Serious Side Effects

While rare, serious adverse effects can occur, particularly in certain high-risk populations:

• Cardiovascular complications:

  • Ventricular arrhythmias
  • Angina
  • Myocardial infarction
  • Pulmonary edema
  • Sudden increases in blood pressure (potentially leading to cerebral hemorrhage, particularly in elderly patients with cardiovascular disease)
  • Tachyarrhythmias 2, 1

• Other serious effects:

  • Injection site reactions (if accidentally injected into digits, hands, or feet)
  • Tissue damage or injury at injection site
  • Rare cases of serious skin and soft tissue infections 1

Risk Factors for Adverse Effects

Certain populations are at higher risk for experiencing adverse effects:

• Patients with heart disease
• Patients with hypertension
• Patients with hyperthyroidism
• Elderly patients
• Patients with Parkinson's disease
• Patients with diabetes
• Patients with pheochromocytoma 2, 1

Route of Administration and Side Effects

The route of administration significantly impacts the risk of adverse effects:

• Intramuscular (IM) injection (recommended route):

  • Lower risk of cardiovascular complications (1.3% risk)
  • Lower risk of overdose 3

• Intravenous (IV) bolus (not recommended for standard use):

  • Significantly higher risk of cardiovascular complications (10% risk)
  • Higher risk of overdose (13.3% risk) 3

Important Considerations

1. Despite potential side effects, epinephrine is the first-line treatment for anaphylaxis with no absolute contraindications in a life-threatening situation 2, 4

2. Even patients with cardiovascular disease should receive epinephrine for anaphylaxis because the risk of untreated anaphylaxis exceeds the risk of epinephrine's cardiac effects 2, 5

3. Between 6-19% of pediatric patients and up to 20% of all patients may require a second dose of epinephrine if symptoms persist or recur 2, 6

4. Proper administration technique is crucial to minimize side effects:

   • Inject into the anterolateral thigh (vastus lateralis muscle)
   • Never inject into buttocks, digits, hands, or feet to avoid tissue damage 1

Dosing Considerations

• Adults and children ≥30 kg: 0.3-0.5 mg (0.3-0.5 mL of 1:1000 solution)
• Children <30 kg: 0.01 mg/kg up to 0.3 mg (0.01 mL/kg of 1:1000 solution) 4

For children weighing 15-30 kg, studies have shown that the EpiPen (0.3 mg) compared to EpiPen Jr (0.15 mg) results in higher systolic blood pressure and more adverse effects, though both achieve similar plasma concentrations 7.

While side effects can occur, they are generally outweighed by the life-saving benefits of epinephrine in anaphylaxis, and delayed administration is associated with poorer outcomes and increased mortality.