With mainstream attention focused on the opioid overdose epidemic in the US, prices for naloxone are rising substantially, leading doctors to call for legislative support to stop unjustified naloxone price increases.
By Thomas G. Ciccone
Interview with Ravi Gupta, BS, and commentary from Jeffrey Gudin, MD, and Jeff Fudin, PharmD
As opioid overdose deaths continue to rise in the US, lawmakers in Washington are pushing to expand access to naloxone, a life-saving agent that can reverse opioid toxicity. But as demand has increased, so has the price of these medications—sometimes at an alarming rate.
According to a new report, Evzio, the first auto-injector formulation for naloxone approval by the FDA in 2014, has risen in price by over 500%. In 2014, a 2-pack of single-use prefilled auto-injectors costed $690.00. Now, it is priced at $4,500.00.1 In addition, Narcan, a newly approved nasal spray version of naloxone, costs $150 for two nasal-spray doses.
In an editorial published in The New England Journal of Medicine,1researchers at Yale University explain that while the federal government has taken steps to encourage expanded access to naloxone, no measures have been taken to ensure pharmaceutical companies don’t gouge naloxone prices.
Naloxone is a safe and effective antidote to accidental opioid overdose. Price escalations could restrict access to this vulnerable population and their caregivers.
“It’s frustrating to see the government’s silence on the rising price of naloxone and the hesitation in holding these pharmaceutical companies accountable,” said Ravi Gupta, BS, lead author of the editorial, told Practical Pain Management.
When Practical Pain Management requested a comment from Kaléo, the manufacturer of Evzio, concerning the nature of the price increase, the company did not offer any explanation. However, according to Mark Herzog, vice president of corporate affairs for the company, Kaléo has changed its access program, allowing all patients and caregivers with commercial insurance and a prescription to access the drug at no cost, regardless if their insurance agrees to pay for the drug.
Naloxone: High Demand, High in Price
In 2015, the Centers for Disease Control and Prevention (CDC) reported that 44 people die from prescription opioid-related toxicity in the United States every day.2 This figure equates to almost 2 deaths every hour. Moreover, 83% of these opioid deaths were unintentional, or at least unanticipated.3
Naloxone is a medication designed to rapidly block the effects of opioids, having first been approved by the US Food and Drug Administration (FDA) back in 1971. The recent CDC guidelines advise doctors to consider co-prescribing naloxone to patients receiving high-dose and/or long-term opioid prescription opioid therapy.4 The White House’s fiscal budget included 12 million dollars in federal grants to states to purchase naloxone. The 2016 Comprehensive Addiction and Recovery Act also calls for more naloxone training and distribution.
“We wrote this piece in particular because as doctors (and as a medical student), we are concerned about the implications of naloxone’s rising price for patient access, especially for such a vulnerable population,” said Mr. Gupta.
Mr. Gupta, a 4th medical student at Yale University, has been working over the past year with coauthor Joseph S. Ross, MD, MSH, on various projects analyzing drug pricing in the US, something that has become a contentious topic, as prescription drugs across the board appear to be trending towards increasingly higher prices.
Each formulation of naloxone—two injection doses, Narcan nasal spray, and Evzio auto-injector—essentially has one supplier, noted Mr. Gupta and Dr. Ross. “Though there are 3 manufacturers with FDA approval for 0.4-mg-per-milliliter-dose injections, the vast majority are sold by Hospira, which has increased the price by 129%, from $62.29 in 2012 to $142.49 in 2016,” they wrote.
Manufacturer Amphastar also increased the price of their 1-mg-per-milliliter injections, which are used off-label as a nasal spray. While the drug had cost $20.34 in 2009, they increased the price by 95% in 2014 to $39.60.
“We wanted to draw more attention to the fact that while federal guidelines and state laws have pushed to expand naloxone availability, they have not directly addressed pharmaceutical companies’ attempt to exploit the situation for greater profits,” Mr. Gupta said.
Curbing Arbitrary Price Increases
As pharmaceutical companies continue to compete for higher profit margins, patient access to life-saving medications, like naloxone, have become marginalized. The notion that insurance companies can respond to these price increases by limiting patient access to naloxone is something Jeffrey Gudin, MD, regards as a “travesty.”
“Naloxone is obviously a life-saving measure in opioid related emergencies. More consideration needs to be given by insurance payers,” otherwise the government should enforce the drug’s distribution, said Dr. Gudin, who is a member of the Practical Pain Management editorial board.
Jeffrey Fudin, PharmD, DAIPM, FCCP, FASHP, also a member of the Practical Pain Management editorial board, today published a response to the editorial, highlighting many of the current problems surrounding naloxone distribution in the US, as well as some of the possible factors driving pharmaceutical companies to increase naloxone prices.
Recently, Senators Susan Collins (R-ME) and Clair McCaskill (D-MO) sent letters to the manufacturers of naloxone drugs demanding explanation for these price increases. However, little action has been taken on the legislative floor of the federal government, leading some states already to take initiative.
For instance, Vermont became the first state to require drug companies to provide detailed reports justifying price increases, specifically for drug prices rising by more than 15% over a 12-month period.
“More transparency into drug pricing is a good start to holding the pharmaceutical industry accountable when they increase drug prices so dramatically,” Mr. Gupta noted. However, while a report of these cost breakdowns will be made available to the public, the names of the drugs will be kept private, a concession to drug companies, which claim that divulging the identities of their products would affect competition.
“This will probably limit the effectiveness of the law. It will also be hard to know whether naloxone is one of the drugs that state officials have looked at. In addition, as far as I can tell, there are no enforcement mechanisms to actually compel pharmaceutical companies to decrease drug prices,” Mr. Gupta noted.
Indeed, while Vermont’s law carries a $10,000 fine for each violation, there is still no recourse to take if drug companies decide to circumvent the state’s legislation by raising prices just below state threshold levels, which conceivably could lead to much higher list prices.
Optimizing Patient Access
There are number of actions the federal government possibly could take to remedy the situation, the simplest of which would be to give naloxone an over-the-counter (OTC) status, something the FDA had been discussing last summer.5 The FDA also could offer incentives to other manufacturers to easily obtain approval for generic naloxone versions, the authors noted.
Regardless of Washington’s inactivity, patients and doctors already have new ways of assessing costs and benefits of pharmaceuticals.
The Institute of Clinical and Economic Review (ICER) is a non-profit organization that develops cost-benefit analysis reports on competing pharmaceutical medications, offering patients and doctors an economic- and evidence-based guideline on the most sustainable treatment solutions available. Just last week, the ICER released a final report on target immunomodulators for plaque psoriasis, summarizing the most affordable, effective pharmaceutical options recommended to clinicians and patients.6
According to Mitchell Stein, policy and communications director for ICER, the institute currently has no plans to review opioid rescue medications. However, the institute is producing a review of abuse-deterrent opioid formulations, which will be released in April.
Disclosure forms related to the authors of the NEJM editorial piece can be accessed through NEJM.org.
- Gupta R, Shah ND, Ross JS.The rising price of naloxone – risks to efforts to stem overdose deaths. N Engl J Med. December 7, 2016.
- Centers for Disease Control and Prevention. Prescription Opioid Overdose Data. http://www.cdc.gov/drugoverdose/data/overdose.html. Published 2016. Accessed August 8, 2016.
- Centers for Disease Control and Prevention. National Center for Health Statistics. Multiple Cause of Death 1999-2014. http://wonder.cdc.gov/mcd-icd10.html. Accessed on August 24, 2016.
- Dowell D, Haegerich TM, Chou R. CDC guideline for prescribing opioids for chronic pain—United States, 2016.JAMA. 2016;315(15):1624-1645.
- Kapczynski A, Kesselheim ‘Government patent use’: A legal approach to reducing drug spending.Health Aff (Millwood). 2016;35:791-797.
- New England Comparative Effectiveness Public Advisory Panel.Targeted immunomodulators for the treatment of moderate-to-severe plaque psoriasis: Effectiveness and Value. 2016. Published on December 2, 2016. Accessed on December 9, 2016.