EpiPen - Drug Monograph

Introduction

EpiPen (epinephrine auto-injector) is a life-saving medical device designed for the emergency treatment of severe allergic reactions (anaphylaxis). It delivers a pre-measured dose of epinephrine, a naturally occurring hormone and neurotransmitter that rapidly reverses the potentially fatal symptoms of anaphylaxis. EpiPen is available in two strengths: EpiPen (0.3 mg) for patients weighing 30 kg or more, and EpiPen Jr (0.15 mg) for patients weighing 15-30 kg.

Mechanism of Action

Epinephrine is a potent alpha- and beta-adrenergic agonist that works through multiple mechanisms to counteract anaphylaxis:

• Alpha-1 adrenergic effects: Causes vasoconstriction, reducing mucosal edema (especially in laryngeal tissues), and counteracting hypotension and shock
• Beta-1 adrenergic effects: Increases heart rate, myocardial contractility, and cardiac output
• Beta-2 adrenergic effects: Promotes bronchodilation, reducing bronchospasm and improving ventilation
• Additional effects: Inhibits further release of inflammatory mediators from mast cells and basophils

Indications

• Emergency treatment of allergic reactions (Type I) including anaphylaxis to foods, medications, insect stings, and other allergens
• Exercise-induced anaphylaxis
• Idiopathic anaphylaxis
• As a bridge to definitive medical care for anaphylactic reactions

Dosage and Administration

• ≥30 kg (66 lbs): 0.3 mg intramuscularly (EpiPen)
• 15-30 kg (33-66 lbs): 0.15 mg intramuscularly (EpiPen Jr)

1. Remove from carrying case 2. Grasp firmly with orange tip pointing downward 3. Remove blue safety release 4. Swing and firmly push orange tip against mid-outer thigh until auto-injector activates 5. Hold in place for 3 seconds (audible click indicates injection start) 6. Massage injection area for 10 seconds 7. Seek immediate emergency medical attention after administration

• Elderly: Use with caution in patients with cardiovascular disease
• Pregnancy: Category C - benefits may outweigh risks in life-threatening situations
• Renal/hepatic impairment: No dosage adjustment required

Repeat doses may be administered every 5-15 minutes if symptoms persist or recur.

Pharmacokinetics

• Absorption: Rapid absorption from intramuscular injection, with peak plasma concentrations achieved within 5-20 minutes
• Distribution: Widely distributed; does not cross blood-brain barrier significantly
• Metabolism: Rapidly metabolized by monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT) in liver and other tissues
• Elimination: Small amounts excreted unchanged in urine; elimination half-life approximately 2-3 minutes

Contraindications

• Known hypersensitivity to epinephrine or any component of the formulation
• There are no absolute contraindications in life-threatening anaphylaxis

Warnings and Precautions

• Use with extreme caution in patients with:

- Cardiovascular disease (angina, arrhythmias, hypertension) - Hyperthyroidism - Diabetes mellitus - Parkinson's disease - Phaeochromocytoma

• May produce severe hypertension and tachyarrhythmias
• Accidental injection into digits, hands, or feet may result in loss of blood flow to affected area
• Ensure proper storage and regularly check expiration date
• Auto-injectors should be visually inspected for discoloration (should be clear) before use

Drug Interactions

• MAO inhibitors: May potentiate effects of epinephrine
• Tricyclic antidepressants: May potentiate cardiovascular effects
• Beta-blockers: May antagonize cardiac effects and potentiate alpha-adrenergic effects
• Digoxin: May increase risk of cardiac arrhythmias
• Ergot alkaloids: May potentiate vasoconstrictive effects
• Thyroid hormones: May potentiate cardiovascular effects

Adverse Effects

• Anxiety, apprehension
• Tremor, dizziness
• Headache
• Pallor
• Tachycardia, palpitations
• Sweating
• Nausea, vomiting

• Myocardial ischemia or infarction
• Severe hypertension
• Cerebral hemorrhage
• Ventricular arrhythmias
• Pulmonary edema
• Tissue necrosis at injection site (if extravasation occurs)

Monitoring Parameters

• Vital signs (blood pressure, heart rate, respiratory rate)
• Oxygen saturation
• ECG monitoring (if available)
• Resolution of anaphylactic symptoms (respiratory distress, urticaria, angioedema)
• Signs of inadequate perfusion
• Injection site for proper administration and potential complications

Patient Education

• Always carry two EpiPens at all times
• Train family members, coworkers, and caregivers on proper administration
• Recognize early signs of anaphylaxis: difficulty breathing, throat tightness, hives, swelling, dizziness
• Administer immediately at first signs of severe reaction
• After administration, call 911 or seek immediate medical attention
• Never hesitate to use EpiPen when anaphylaxis is suspected
• Replace unit before expiration date
• Store at room temperature (20-25°C/68-77°F); avoid extreme temperatures
• Practice with trainer device (without needle or medication)
• Wear medical identification jewelry indicating allergies

References

1. Simons FER, Ardusso LRF, Bilò MB, et al. World Allergy Organization guidelines for the assessment and management of anaphylaxis. World Allergy Organ J. 2011;4(2):13-37. 2. Lieberman P, Nicklas RA, Randolph C, et al. Anaphylaxis—a practice parameter update 2015. Ann Allergy Asthma Immunol. 2015;115(5):341-384. 3. EpiPen [package insert]. Morgantown, WV: Mylan Specialty LP; 2020. 4. Kemp SF, Lockey RF, Simons FE; World Allergy Organization ad hoc Committee on Epinephrine in Anaphylaxis. Epinephrine: the drug of choice for anaphylaxis. A statement of the World Allergy Organization. Allergy. 2008;63(8):1061-1070. 5. Sicherer SH, Simons FER; Section on Allergy and Immunology. Epinephrine for first-aid management of anaphylaxis. Pediatrics. 2017;139(3):e20164006. 6. Campbell RL, Li JT, Nicklas RA, Sadosty AT; Members of the Joint Task Force; Practice Parameter Workgroup. Emergency department diagnosis and treatment of anaphylaxis: a practice parameter. Ann Allergy Asthma Immunol. 2014;113(6):599-608.