EpiPen or Epinephrine Auto-Injector is a combination product containing drug and device components. This is a first-line treatment for anaphylaxis, an allergic medical emergency that results in hives and swelling, wheezing, breathing difficulty or swallowing difficulty due to throat swelling, drop in blood pressure (hypotension), fainting, chest tightness, nausea, vomiting, stomach cramps, paleness or redness of the skin.
Each EpiPen Auto-Injector delivers a single dose of epinephrine injection in a sterile solution. Epinephrine acts quickly to improve breathing, stimulate the heart, raise a dropping blood pressure, reverse hives, and reduce swelling of the face, lips, and throat.
Prescription Name and Overview
EpiPen 0.3 mg and EpiPen Jr 0.15 mg are prescription-only drugs used in emergencies as a treatment for allergic reactions. The EpiPen 0.3 delivers a single dose of 0.3 epinephrine in a sterile solution while the EpiPen Jr delivers a single dose of 0.15 mg epinephrine in a sterile solution.
This medication is prescribed for use in emergency medical treatment for life-threatening allergic reactions caused by insect bites or stings, foods, medications, and other causes. It comes in an auto-injector pen that can be given through the thigh and even through clothing.
Alternatives to the EpiPen include the generic copy provided by Mylan, the slightly different design provided by Adrenaclick, and another product from Auvi-Q.
Generic Name and Overview
In August 2018, Teva Pharmaceuticals was approved to manufacture the first generic version of EpiPen and EpiPen Jr amidst controversy about the very high price of the life-saving drug. The generic version is available in 0.3 and 0.15 mg strengths, with the same packaging and same direction for usage with the branded EpiPen.
Authorized generic EpiPen contains the same drug (epinephrine) and is put in the same device as the branded ones. The difference is that it doesn’t have the label “EpiPen” on the packaging. An authorized generic for EpiPen is manufactured by the same manufacturer who makes the branded ones. Under the existing New Drug Application (NDA) approved by the FDA, the manufacturer may use the same plant and device, and may sell an authorized generic version of their product.
OTC Name and Overview
In the United States, you cannot buy EpiPen over the counter without having a written prescription from a doctor. Although some schools do have stocks of the product for emergency purposes, use of the product will be administered under the direction of a health care personnel.
In other countries like Canada, you can purchase EpiPen without a written prescription from your doctor.
Manufacturer
Epipen is manufactured by Meridian Medical Technologies, a subsidiary of Pfizer, and marketed by Mylan.
Labeled Indications
EpiPen (Epinephrine) Auto-Injector and EpiPen Auto-Injector Jr. are indicated in the emergency treatment of type 1 allergic reactions, including anaphylaxis to:
- Insect bites or stings
- Foods
- Drugs
- Diagnostic testing substances
- And other allergens including idiopathic anaphylaxis or exercise-induced allergy
Both the EpiPen and EpiPen Jr Auto-Injector are intended for emergency supportive therapy only and is not a substitute for immediate medical care.
Active Ingredients
The active ingredient for EpiPen Auto-Injector is epinephrine.
What Is It Used For?
EpiPen is the drug of choice for the emergency treatment of severe allergic reactions to insect stings or bites, foods, drugs, and other allergens. It can also be used in the treatment of anaphylaxis of unknown causes (idiopathic anaphylaxis) or exercise-induced anaphylaxis.
How Does it Work?
Once the shot is given on the thigh, EpiPen works rapidly but on a short duration of only. It should not be injected on the buttocks, hands, feet, or other areas other than the thigh. The drug may not work properly if administered somewhere else.
EpiPen is a kind of epinephrine auto-injector, which means it delivers epinephrine automatically by injecting a dose of the hormone epinephrine, a man-made version of adrenaline. Adrenaline is the body’s natural hormone released in response to stress.
When a person has an allergic reaction to something, the immune system releases a lot of chemicals to combat an allergen. These flood of chemicals may cause life-threatening reactions to the body including a drop in blood pressure, swelling of the face, mouth and tongue, constricted airways, and others. Death could result once a person’s airway gets blocked and he/she could not breathe or if the heart stops beating.
Epinephrine works by causing blood pressure to constrict and raising the blood pressure, improve breathing by relaxing the airways, stimulating the heart to improve blood flow, reversing hives, and reducing the swelling of the face, lips, and throat.
What are the Approved Uses?
EpiPen is used for the emergency treatment of the signs and symptoms of anaphylaxis, including pruritus, urticaria, angioedema, flushing, syncope, tachycardia and dyspnea due to laryngeal spasm and/or decrease in blood pressure.
Use epinephrine injection exactly as directed; do not inject it more often or less than prescribed by your doctor.
Production Anecdotes / History
Autoinjectors were first used for the purpose of rapid administration of antidotes for nerve gas. The first epinephrine auto-injector, EpiPen, was invented in the 1970s at Survival Technology in Bethesda, Maryland by Sheldon Kaplan. In 1987, FDA approved its marketing.
1996 saw the merging of Survival Technology and Brunswick Biomedical. The new company was called Meridian Medical Technologies, Inc. in 1997, Dey, a subsidiary company of Merck KGaA, got the exclusive right to sell and distribute the product. In 1998, a massive recall happened, with one million EpiPens, happening twice that year.
In 2007, Mylan got the right to market and sell EpiPen from Merck KGaA and in 2009, Mylan and King started marketing a better version of Epipen with better safety features, instructions, and sturdier spring.
Since 2009, EpiPen’s price has raised drastically. In 2009, the price of two EpiPens was about $100; by July 2013, it became $265; in May 2015, the price has risen to around $461; and in 2016, the price rose again to around $609. Wide criticisms rang out because of this. In October 2016, Mylan announced a $465 M settlement with the US as rebates.
On September 5, 2017, FDA issued a warning to Meridian Medical Technologies, Inc., for failing to investigate and recall bad batches of the devices that were reported. They have also failed to conduct follow up on several problems with the device such as failure of the spring to push out the needle caused hundreds of deaths. When the FDA inspected the production sites, the Meridian employees didn’t allow the inspectors to disassemble the products because the management has not approved such things.
Precautions
Before using the epinephrine injection:
- Tell your doctor or pharmacist if you have any allergy to epinephrine, any other medication, sulfites, or any of the other ingredients in epinephrine injection. You may be advised to use the injection even if you’re allergic to some of the ingredients because it is a life-saving medication. You may note that EpiPen does not contain any latex and is safe to use if you have latex allergy.
- Inform your doctor if you are taking other prescription medicines, non-prescription medicines, vitamins, supplements, or herbal products.
- Inform your doctor if you’ve had chest pains, irregular heartbeat, high blood pressure, heart disease, asthma, diabetes, hyperthyroidism, adrenal gland tumor, depression, other mental illness, or Parkinson’s disease.
- Tell your doctor if you are pregnant, planning to get pregnant, or are breastfeeding. Ask your doctor whether you may use an epinephrine injection while pregnant.
Epinephrine injections are not a substitute for immediate medical care. In conjunction with the administration of epinephrine, the patient should seek immediate medical or hospital care. More than two sequential administrations of the product should only be done under direct medical supervision.
Long-Term Use Considerations
The considerations for long-term use includes the high cost of the Epinephrine auto-injectors and the lack of epinephrine availability among patients.
The FDA has been receiving reports of the drug both on the side effects and device failure. The most reported serious complications reported between 1993-2017 are:
- Accidental exposure- 806 cases reported
- Device failure- 645 cases reported
- Drug ineffective- 462 cases reported
- Expired product administered- 320 cases reported
Drug Interactions
Drug interactions happen when a substance that you are taking changes or disrupts how a medication or drug should work. Interactions may be harmful to you, increase your risk for serious side effects, or inhibit a drug from functioning properly. Always consult your doctor if you are going to start a medication with a new drug.
Can Interact with the Following
Patients who receive epinephrine while 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, tripe-lennaine 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 alpha-adrenergic blocking drugs, such as phentoloamine. Ergot alkaloids may also reverse the pressor effects of epinephrine.
Can’t Interact with the Following
There are no absolute contraindications to the use of epinephrine in life-threatening situations.
When To Stop Taking
Since this drug is used to treat allergic reactions in life-threatening situations, there is no reason to stop taking the drug. Take note that you can’t have more than 2 shots administered in between 5-15 minutes unless under the direct supervision of a medical professional.
You may only stop taking the drug upon the explicit direction of your doctor, or if you develop severe reactions to the medicine. Ask your doctor for a replacement drug for EpiPen in case you need an immediate treatment for an allergy.
Long-Term Side Effects
Patients who use EpiPen while taking cardiac glycosides, diuretics, or anti-arrhythmics should be observed carefully for the development of cardiac arrhythmias.
Those with hypertension or hyperthyroidism may develop more severe and longer lasting side effects. There are rare cases of infection of the injection site after EpiPen use, including necrotizing fasciitis and myonecrosis caused by gas gangrene.
There were reports that the use of EpiPen has triggered obsession, anxiety and depression in children and teenagers. The effect could last for up to a month after the EpiPen injection.
FDA Warnings (History Of)
On April 2017, US FDA issued a wide recall of EpiPen products, joining a global recall of the potentially life-saving drug.
The recall was made due to hundreds of reports of the defective device failing to inject the dose of epinephrine. FDA states that a defective part failed to trigger the needle from coming out. 13 batches of EpiPen and EpiPen Jr. that were distributed between December 17, 2014 and July 1, 2016 were recalled.
Mylan has already recalled 80,000 EpiPens in Australia, Europe, Japan and New Zealand after two instances of the device failing to launch the needle during an emergency were reported. The EpiPen is designed to launch a needle once the device is pressed onto a person’s thigh. The defective parts may prevent the product from working at all, or may require increased force to activate the needle.
As of June 2018, the FDA has received 2,810 negative reports about the side effects and device-related complications of EpiPen. More than half of these reports are serious cases that included 126 deaths.
Other Common Side Effects
EpiPen Auto-Injector may cause side effects. When you get emergency medical treatment after you inject epinephrine, tell your doctor if you are experiencing any of these common side effects:
- Redness, tenderness, or swelling at the injection site
- Difficulty breathing
- Fast, irregular, or pounding heartbeat
- Nausea
- Vomiting
- Profuse sweating
- Dizziness
- Anxiety, nervousness, restlessness
- Weakness
- Pale skin
- Headache
- Uncontrollable shaking of any part of your body
Infrequent side effects:
- High Blood pressure
- Arrhythmia
- Angina
- Chest Pain
- Disease of Inadequate blood flow to the heart
- Disease of the muscle of the heart with enlargement
- Escape of intravenous medications into surrounding tissues
- Gangrene
- Heart attack
- Heart ventricle rhythm problem
- Hemorrhage within the skull
- High blood sugar
- Increased blood acidity due to high levels of lactic acid
- Infection at injection site
- Reduced kidney function
- Fluid in the lungs
- Low amount of potassium in the blood
- Low blood sugar
- Necrotizing fasciitis
- Paradoxical bronchospasm
- Stroke
- Supraventricular tachycardia
- Ventricular fibrillation
- Ventricular premature beats
Lawsuits
In September 2016, several lawsuits were filed against Mylan, the maker of EpiPen under a law that’s typically used to take on organized crimes.
Several class-action cases against the drugmaker were brought in Kansas and northern California after Mylan raised the price of the EpiPen injectors by 500% since 2008. Hundreds of people have signed on the class-action case. A month later, Mylan announced that it will settle with the US Department of Justice and other government agencies with $465 million. This was to resolve the issue that Mylan classified EpiPen as a generic drug under Medicaid so that Mylan would get a lower rebate for it and “reap huge profits at the expense of taxpayers” according to Sen. Richard Blumenthal.
In 2017, FDA sent a warning letter to Mylan due to the fact that hundreds of complaints filed against the EpiPen products which” failed to operate properly during life-threatening emergencies including some situations which patients subsequently died”, the agency wrote.
The FDA went on to add that “Nonetheless, on June 3, 2016, you concluded that the defect was infrequent, even though you had not examined all of your reserve samples to determine the extent of the defect within the same lot of finished products, nor did you expand your investigation to other lots…you closed your investigation and determined that “no market action would be taken.”
Some common device-related complications that were reported to the FDA were:
- Accidental injection to the body other than the thigh
- Device failure
- Rare but serious skin infection on the injection site
- Lacerations and bent or embedded needles in young children who move during the injection
- Allergic reaction to sulfite, a chemical that prevents the solution from turning brown
Days after the inspection of the FDA, Mylan recalled thousands of EpiPen batches. Although EpiPen has been hit with the class-action lawsuit for its pricing practices, no formal lawsuit about the defective products have been formally made yet.
https://www.webmd.com/drugs/2/drug-20017/epipen-injection/details
https://www.drugs.com/article/epipen-cost-alternatives.html
https://www.fda.gov/drugs/drugsafety/ucm624986.htm
https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/019430s053lbl.pdf
https://www.allergyeats.com/after-the-epi-our-real-nightmare-begins/
