Naloxone: How much is it worth to save a life?

When the life-saving properties of naloxone entered the world more than four decades ago, nobody realized how valuable it would become. The drug itself costs pennies, and is used regularly in hospitals to reverse sedation and anesthesia, as well as in emergency settings to rescue people from opioid overdoses. Then the opioid epidemic took over the nation and, starting a few years ago, naloxone became increasingly important for harm reduction activists and first responders to have on hand. It also became obvious that it would be a good medication for families of opioid users to have in case of an accidental overdose, even of a prescription pain medication, and for families of patients newly enrolled in opioid treatment programs.

But this brought the medication into a new arena. The only naloxone currently approved by the Food and Drug Administration (FDA) is available in vials (which require a needle and syringe) or pre-filled syringes—both requiring medical expertise to inject—or, more recently, in a very expensive auto-injector that does not require medical expertise.

And with the new arena came new marketing opportunities, apparently, because the price of naloxone doubled about a year ago. This has created some bitterness from buyers who see a pharmaceutical company gouging at a time of need. Currently there is only one supplier, although two other naloxone products are undergoing FDA review.

Before the availability of the auto-injector, approved in April 2014, many people (including addiction treatment professionals) had figured out how to use the vial without a needle. By connecting it to an intranasal atomizer, they could administer the naloxone into the nose, and rescue the victim that way. However, the FDA has not approved this as a delivery method, so neither the FDA nor Amphastar Pharmaceuticals, which makes the naloxone vials and prefilled syringes, can talk about it.

More than two years ago, pharmaceutical company Endo, which made naloxone trade-name product Narcan, stopped selling it. There have been shortages, but ever since naloxone's price doubled last year, there seems to be plenty to go around. A year ago it cost about $50 to get a naloxone kit, consisting of an atomizer and the medication. Now it costs about $100. The Evzio auto-injector costs more than $500.

Addiction Professional spoke for this article with a treatment program that started the first large naloxone buying and training programs using the atomizer; the founder of Kaleo, which makes the Evzio auto-injector; and a purchasing cooperative that buys naloxone for mayors, governors and counties, about the hard realities of this drug.

Not-for-profit initiative

Naloxone as a commonly used overdose rescue drug came into its own more than three years ago when Gil Kerlikowske, then director of the Office of National Drug Control Policy (ONDCP), traveled to North Carolina to promote use of the medication along with Fred Wells Brason II, executive director of Project Lazarus, a not-for-profit organization focusing on rescuing overdose victims. At the time, naloxone manufacturers were being pressured by the federal government to increase production of the drug. Project Lazarus provides kits that include two doses, atomizers, and instructions.

Project Lazarus doesn’t directly provide the naloxone; it provides the prescription for two doses, which the pharmacy has to fill. The kit costs $12. The cost of the naloxone is $39 per dose, says Brason. It’s always important to have two doses, because one may not be enough to rescue the victim. In some states, Medicaid will cover the atomizer. Sometimes insurance covers the naloxone. Project Lazarus also has had grants available in the past.

“We sell a few thousand kits a year, to law enforcement, to anybody who wants them,” says Brason. “Until there are sufficient products out in the marketplace, we’ll do what we need to do in order to save a life.”

There was an “outcry” when Amphastar doubled the price of naloxone a year ago, said Brason. Likewise, there is consternation about the high cost of the Evzio auto-injector. But Brason blames the healthcare system, adding that very few people actually pay the listed price.

“When a new product comes out and they determine what their pricing needs to be, they need to bring it up to a certain ceiling, because then they negotiate rates with Medicaid, and private payers,” he says.

The two products currently under FDA review are both intranasal—one is a single device that doesn’t require an atomizer. Nobody knows for sure what the pricing will be, says Brason, but most expect that competition will keep prices down.

When the FDA approved the auto-injector as a take-home device, it did so without any requirement that there be a diagnosis accompanying the prescription, says Brason. “That was a great thing.”

He believes in co-prescribing, so that any patient who gets a prescription from a physician for an opioid would also get a prescription for naloxone. “Having naloxone readily available is necessary to prevent death, in case a patient makes a mistake” with an opioid prescription, he says. It’s also preventing death in someone who was formerly addicted and hasn’t used opioids recently, but goes back to the drug and takes too much by mistake, not realizing how the tolerance level has changed.

“I want it to be mainstream,” Brason says of naloxone.

Auto-injector

Eric Edwards, MD, PhD, medical director of auto-injector manufacturer Kaleo, couldn’t agree more. That’s why the Evzio device automatically injects the drug, with no needle ever exposed or seen. The device even gives instructions. He compares the technology to that of defibrillators, which can save people who are having heart attacks.

“What was it that enabled the defibrillator to be on the wall of every airport, in every public space? The answer is, the technology that shows every layperson can do it directly,” says Edwards.

As for pricing, Edwards says insurance companies pay for most of it. He compares it to the epinephrine autoinjector (the Epi-Pen), used by people with food allergies to avert and rescue from anaphylactic shock. “Epinephrine in a syringe is 22 cents, but the autoinjector is $500,” he says. However, Medicaid and virtually every insurance plan cover the epinephrine autoinjector.

Before Edwards started Kaleo, he was a paramedic; then he went to medical school and his twin brother went to engineering school. “We both saw a huge need for technologies that could enable broader access and early intervention for acute care drugs,” he says. Later, when he was serving as an intern in the emergency department, a 62-year-old woman came in with 22 fentanyl patches on her back—nobody had told her to remove one before putting on the next. She wasn’t breathing, but was revived with naloxone.

“Prescription opioid overdoses can affect children, the elderly, and everyone in between,” says Edwards. “The problem is when an emergency occurs, and you stop breathing, seconds count. The earlier you can administer naloxone, the better your chance of avoiding intubation, the ICU, and death.”

With insurance approval, the price actually paid by the patient for the auto-injector goes down, says Edwards. “The median out-of-pocket cost is $17,” he says. “The VA put Evzio on the formulary immediately. And we have 80% coverage by commercial insurance.” In almost all states, Medicaid covers Evzio, he says. However, half the states have varying degrees of hurdles.

One Evzio package includes two auto-injectors and a trainer. The wholesale cost is $575, but “nobody pays that,” says Edwards. For people who don’t have health insurance, Kaleo has a prescription assistance program, he says.

Edwards is glad that there are intranasal products going through the FDA review process. “That’s the right way to do it,” he says. “I don’t know why people aren’t thinking about the fact that now, using the intranasal product, they’re using something that isn’t FDA-approved.”

Four delivery models

Unlike most medical treatments, naloxone has four very different delivery models:

• Law enforcement. It’s most likely for police officers to respond to heroin overdoses, says Edwards. They are not as likely to respond to cases in which someone has, for example, mixed alcohol with prescription opioids.

• Harm reduction, needle exchange clinics, treatment programs, public health workers. These are the people on the “front lines” who distribute naloxone to people at high risk for overdose.

• Pharmacies. Many states are now allowing pharmacists to furnish or dispense naloxone, either through a collaborative practice agreement or a standing order, for anyone who comes in with an opioid prescription.

• Physician prescriptions. This is the model that is appropriate for the auto-injector, in which the physician would have a conversation with a patient and would prescribe, says Edwards. This could be for a pain patient or a patient in recovery from an opioid use disorder.

Purchasing alliance

Last month, The U.S. Communities Purchasing Alliance and Premier, Inc., announced a cooperative purchasing initiative to help expand access to naloxone. The initiative will guarantee discounts for members of the National Association of Counties, the National League of Cities and the U.S. Conference of Mayors. The program also includes access to buprenorphine and other medications.

Chris Robb, general manager of U.S. Communities, says the purchasing cooperative was created by the counties and other associations such as the National Governors' Association “to aggregate purchasing power and to simplify the procurement process.”

“Whether a small town or a large city, a university, you need to make it simple for first responders to get this product and do so without going through the long competitive bid process,” says Robb.

He would not disclose specific pricing information, but says, “Every agency is different depending on the distribution cost, which is based on location.” There is no cost to register for the program.

What about treatment?

The bottom line, however, is that funding needs to be provided for treatment, says Project Lazarus's Brason, noting that naloxone isn’t treatment for an opioid use disorder.

“Treatment funding has been cut,” he says. “When you look at the fact that they were going to give the CDC $50 million for enhancing prescription monitoring, you have to ask where the doctors are going to send people” who no longer can get opioids.

Brason adds, “If they just say, ‘I’m not going to write you any more prescriptions,' and there’s no treatment, they’re just sending them out into the street.”