Epinephrine for Anaphylaxis: What Pharmacists Should Know

Epinephrine has been a hot topic in the news lately because of the EpiPen’s increasing cost.

The first epinephrine auto-injector was invented in the mid-1970s and approved in 1987. Yet, since Mylan purchased EpiPen in 2007, the product has increased in price by more than 400%, which has sparked public outrage and inquiries from Congress.

Despite EpiPen having an 85% market share, there are still several other epinephrine formulations commercially available, with future generics to come. Here are several key therapeutics areas for epinephrine every pharmacist should know:

Indication

Epinephrine is indicated for the emergency treatment of allergic reactions (Type I), including anaphylaxis, which is defined as an acute, life-threatening allergic reaction. It can be triggered by insect stings or bites, foods, drugs, and other allergens, or it can be idiopathic or exercise-induced. Signs and symptoms include trouble breathing, hives or swelling, tightness of the throat, nausea, vomiting, abdominal pain, dizziness, and rapid heartbeat.

The estimated prevalence of anaphylaxis is 1% to 2%, with many studies suggesting increasing numbers. Food allergies in children alone account for more than 200,000 emergency department visits every year and an economic burden of nearly $25 billion per year.

Epinephrine, either as a prefilled auto-injector or drawn with a syringe, is the treatment of choice for anaphylaxis. It’s recommended to be given at the first sign of anaphylaxis, regardless of cause.

Mechanism of Action

Epinephrine is a nonselective alpha- and beta-adrenergic receptor agonist. Through its action on alpha-adrenergic receptors, it reduces vasodilation and increases vascular permeability that occurs during anaphylaxis. Its action on beta-adrenergic receptors results in bronchial smooth muscle relaxation, which helps alleviate bronchospasm, wheezing, and dyspnea that may occur during anaphylaxis.

Epinephrine also reduces 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 bladder.

Formulations

EpiPen auto-injectors (epinephrine injections, 1:1000) are available as a 2-pack of 0.3 mL EpiPen auto-injectors and one trainer device. EpiPen Jr auto-injectors (epinephrine injections, USP, 1:2000) are available as a 2-pack of 0.3 mL EpiPen Jr auto-injectors and one trainer device.

Adrenaclick epinephrine auto-injectors are available as a carton containing 2 0.3 mg or 0.15 mg auto-injectors. A separate trainer device may be requested through the company’s website or phone center. The authorized generic epinephrine auto-injector of Adrenaclick was released in May 2010, but it isn’t AB rated by the FDA and therefore can’t be interchanged for any other epinephrine product.

Product Comparison

Name

Formulation

Co-pay Card

AWP (28 days)

EpiPen

Auto-injector

Yes: up to $300 savings for each EpiPen 2-Pak carton

$730

Epinephrine

Auto-injector

Yes: max savings of $100

per pack (limit 3 packs)

$494

Adrenaclick

Auto-injector

No longer marketed

Auvi-Q

Auto-injector

Recalled in 2015

Twinject

Auto-injector

Discontinued by manufacturer in 2012

Adrenalin solution

Vial

N/A

$15

Epinephrine HCl solution

Vial

N/A

$1.52

Cost based on AWP, per Lexi-Drugs. Cost to the patient will vary based on individual insurance coverage.

Storage

Epinephrine auto-injectors should be stored in the carrier tube provided to protect them from light. Don’t refrigerate the devices.

Dosing

Appropriate dose should be determined based on patient body weight. Patients ≥30 kg should be prescribed the 0.3 mg strength, while those 15 kg to 30 kg should use the 0.15 mg strength.

Administration

Each auto-injector contains a single dose of epinephrine for single-use injection. More than 2 sequential doses of epinephrine should only be administered under direct medical supervision.

The auto-injector should be injected either intramuscularly or subcutaneously into the anterolateral aspect (mid to upper) area of the thigh, through clothing if necessary. The injection should not be given into the buttock, as this may not provide effective treatment of anaphylaxis and may increase the risk of Clostridial infection.

Caregivers of young children who may be uncooperative and kick or move during an injection should be instructed to hold the leg firmly in place to limit movement before and during the injection.

Epinephrine auto-injectors are intended for immediate administration as emergency supportive therapy and aren’t a substitute for immediate medical care, which patients should seek after use.

Safety

Adverse effects include increased heart rate, palpitations, sweating, nausea and vomiting, difficulty breathing, pallor, dizziness, weakness or shakiness, headache, apprehension, nervousness, or anxiety. These signs and symptoms usually subside rapidly, especially with rest.

Patients with coronary artery disease could experience angina, while those with diabetes may develop increased blood glucose levels following epinephrine administration. Patients with Parkinson’s disease may notice a temporary worsening of symptoms.

Patient Counseling

Before use, patients should be instructed to make sure the solution in the auto-injector is clear and colorless. If the solution is discolored, cloudy, or contains particles, the auto-injector should be replaced.

Expiration dates are printed on the sides of the auto'injectors. As the effectiveness of epinephrine may decrease after the expiration date, patients should be instructed to promptly refill their prescription before it.

Future Formulations

Mylan is expected to release a generic formulation of EpiPen that will cost half of the brand-name version sometime in September 2016.

Teva Pharmaceuticals has been working on releasing a generic EpiPen for a number of years. It applied for a generic in 2009, but was sued for patent infringement and agreed to wait until mid-2015 to reapply. In April 2016, Teva announced that the FDA had rejected the filing citing “certain major deficiencies.” The company’s current timeline to introduce a generic EpiPen is 2018.

Conclusion

Epinephrine is highly effective for anaphylaxis. Although costly, the auto-injectors provide ease of use for patients and caregivers. Future generic formulations are expected to be released, which will help lower costs.