How well do EpiPens work?

Last month’s column discussed Heather Bresch, CEO of Mylan Pharmaceuticals, and her plan to maximize corporate profits with a 620 percent EpiPen price increase over nine years to $610 for two pens. This month’s column looks at the evidence on how well the EpiPen works.

Since last month, the company agreed to pay the government $465 million to correct its excess Medicaid reimbursement. Bresch also testified to the House Oversight and Government Reform Committee that Mylan “only makes” $100 per package of two pens. This figure includes overhead.  My estimate of the direct costs to make the EpiPen is less than $10.

The extra $600 charge is for the EpiPen’s patented design. Anaphylaxis is a life threatening allergic reaction that can cause swelling of the throat, low blood pressure, shock and death. Epinephrine quickly constricts the blood vessels and raises the blood pressure. An auto injector pen like the EpiPen has the ability to help people quickly inject the epinephrine into a muscle and reverse the anaphylaxis.

Physicians have been using epinephrine to treat anaphylaxis for over 50 years. Like many older medications, it is believed to be effective based on clinical experience. Because anaphylaxis is a life threatening condition, it would be unethical to do a randomized trial with placebo and very hard to do a randomized trial with a new unproven alternative medication.

Auto injectors like the EpiPen allow rapid delivery of epinephrine into the muscle with only modest training. Getting FDA approval for a different pen design requires millions of dollars of funding and months to get approved. To gain market share, EpiPen was promoted through an EpiPen 4 School program. Switching to a competing pen requires a new school training program.  The pens are not foolproof. For example, there is some risk of injecting into the bone instead of the muscle.

Although EpiPen has had about 85 percent market share, studies comparing different brands of pen found patients do not always prefer the EpiPen. After years of promoting EpiPens, the number of people with anaphylaxis seen in emergency departments that have used EpiPens is low. Only 10 percent of patients with EpiPens use the EpiPens when symptoms first appear and only 30 percent use the pens during an anaphylactic episode. Another limitation is the pens expire in one year.

The lowest cost method of administering epinephrine is to purchase ampules. Two vials and two syringes can be purchased for less than $20. However, in an emergency an ampule needs to be broken open and the epinephrine must be drawn up in a syringe. This method requires more training and expertise to use. It also takes longer.

Epinephrine appears to be the best medication and an easy delivery system like the EpiPen is desirable. Based on the direct cost of manufacturing, the cost should be much cheaper. Our government should also promote competition to help manage prices and save lives.

Selected References

1. Cnn Money – http://money.cnn.com/2016/10/07/news/companies/epipen-mylan-465-million-fine/
2. Mole, Beth: Mylan CEO misled lawmakers about EpiPen profits—they’re 66% higher Bresch insists Mylan only makes $100 a pen by hiding behind unrealistic tax rate. 9/26/16 ARS Technica http://arstechnica.com/science/2016/09/mylan-ceo-misled-lawmakers-about-epipen-profits-theyre-66-higher/
3. Alexandra Rosenmann. Mylan CEO Heather Bresch Disastrously Defends EpiPen Price Hike and her Own 16M Pay Raise.  Aug 25^th  Alternet.
4. Hogue SL, Goss D, Hollis K, Silvia S, White MV: Training and administration of epinephrine auto-injectors for anaphylaxis treatment in US schools: results from the EpiPen4Schools(®) pilot survey. J Asthma Allergy. 2016 Jun 17;9:109-15.
5. Dreborg S, Wen X, Kim L, Tsai G, Nevis I, Potts R, Chiu J, Dominic A, Kim H: Do epinephrine auto-injectors have an unsuitable needle length in children and adolescents at risk for anaphylaxis from food allergy? Allergy Asthma Clin Immunol. 2016 Mar 6;12:11.
6. Camargo CA Jr, Guana A, Wang S, Simons FE : Auvi-Q versus EpiPen: preferences of adults, caregivers, and children.  J Allergy Clin Immunol Pract. 2013 May-Jun;1(3):266-72.
7. Brown J, Tuthill D, Alfaham M, Spear E: A randomized maternal evaluation of epinephrine autoinjection devices.  Pediatr Allergy Immunol. 2013 Mar;24(2):173-7
8. Bakirtas A1, Arga M, Catal F, Derinoz O, Demirsoy MS, Turktas I: Make-up of the epinephrine autoinjector: the effect on its use by untrained users. Pediatr Allergy Immunol. 2011 Nov;22(7):729-33.
9. Alexandre Ackaoui: Treatment of anaphylaxis : EpiPen, Twinject, or another autoinjector?  Can Fam Physician. 2011 Mar; 57(3): 273.