Naloxone auto-injector approval important step to saving lives

The first auto-injector for naloxone, an overdose reversal medication, was approved by the Food and Drug Administration (FDA) on April 3. The consumer-friendly device will be available by prescription only, and the main target is family members and caregivers of patients prescribed opioids. Naloxone reverses the effects of opioids and has already saved thousands of lives used by syringe injections or intranasal spray, especially by harm reduction advocates who target street overdoses of heroin.

The auto-injector, called Evzio and fast-tracked by the FDA because of the opioid overdose epidemic, works on all opioids, heroin and prescription medications. But because five times as many deaths occur on prescription opioids compared to heroin, Evzio fills a much-needed gap, federal officials said.

“People are dying,” said Margaret A. Hamburg, M.D., commissioner of the FDA, in a press call announcing the approval. And she stressed that anybody can use Evzio–not only the person it is prescribed for. “We recognize that sometimes this will be used in the context of a specific patient, but we have no intention of prohibiting the use of naloxone by first responders, family members, caregivers, and anyone for whom a product wasn’t prescribed,” said Hamburg.

The naloxone auto-injector is an “important new tool,” said Douglas Throckmorton, M.D., deputy director of regulatory programs at the FDA. And while the “larger goal” is to prevent opioid addiction and abuse, the auto-injector will help save lives, he said. But use does not negate the need for 911 calls when Evzio is used.

There are many jurisdictions in which first responders and harm reduction advocates carry intranasal naloxone spray--or rather, they carry the liquid in a vial, and then use an atomizer which they can use to spray it into the nasal passages. It’s an off-label, makeshift use, but it works. The main other delivery device is via syringe, which requires medical training.

The auto-injector provides another option, said Michael Botticelli, director of the Office of National Drug Control Policy, adding that for many people, law enforcement is the first responder to an overdose. Whether they use the new auto-injector or other devices, all first responders should carry naloxone, he said. “We encourage law enforcement to train and equip first responders” with naloxone, said Botticelli. “We know they understand that saving a life is more important than making an arrest.”Obviously, emergency medical technicians are able to use the syringe but in many cases, it will be easier for non-medical first responders to use an auto-injector, or intranasal spray.

Intranasal formulation work in progress

Wilson Compton, M.D., deputy director of the National Institute on Drug Abuse (NIDA), called the auto-injector a “milestone.” At the same time, he said that NIDA is working on research on intranasal formulations. “This is a situation where states and local practitioners have been ahead of the developers,” said Compton. “That’s why we’re working so hard at NIDA to develop an intranasal formulation that can be approved by the FDA,” he said.

Harm reduction advocates have come up with other ways to deliver naloxone to overdose victims, including the makeshift liquid and atomizer kits. “Faced with an epidemic of overdoses, the field has gotten ahead of the FDA,” said Melinda Campopiano, M.D., medical officer for Substance Abuse and Mental Health Service Administration’s Center for Substance Abuse Treatment. The hope is that with an easier-to-use FDA-approved device, uptake of naloxone prescribing whether due to illicit drug use or prescriptions will increase, she added. Last fall, SAMHSA released an opioid overdose prevention manual, which provides advice about when to administer naloxone.

Treatment itself is an overdose reduction strategy, noted Botticelli, who said that when Baltimore, a city with a high rate of heroin addiction, expanded buprenorphine treatment, there was a reduction in overdose deaths. “We are looking at how to continue the focus on the uptake of medication-assisted treatment,” said Botticelli. “We’re also looking at innovative models to expand access, particularly to buprenorphine, and some other work we’re doing to expand access to medication-assisted treatment.”

According to NIDA’s Compton said that there are many barriers to medication-assisted treatment, including requirements that patients fail at other less expensive treatments or have onerous co-pays. “We’re working on this,” he said.

Critics of widespread availability of naloxone – including the governor of heroin-ravaged Maine--think that it will encourage drug use. There is no evidence of this, said the FDA’s Throckmorton. “First and foremost, this is about saving a life,” he said. Secondly, going through withdrawal, which naloxone would precipitate in a regular opioid user, is “not a pleasant experience,” he said. “That would serve as a disincentive” to use naloxone as a mechanism to continue abuse. Instead, the rescue should lead the person to seek medical attention and “discuss what led you to overdose on your prescription drug,” he said.

Other federal initiatives

Also speaking on April 3, Kathleen Sebelius, outgoing secretary of the Department of Health and Human Services., stressed that many people rely upon an appropriate use pain medication. “In that light, HHS is pursuing a comprehensive strategy that protects those people while looking at the small minority that drives the abuse epidemic,” she said.

In addition to educating prescribers and supporting research into non-addictive and tamper-resistant pain medications, HHS is working to help people who are addicted and need treatment.

Evzio is not meant to compete with the work being done by harm reduction groups that focus on getting naloxone into the community by whatever means possible, notes Eric Edwards, M.D., Ph.D., medical director of Richmond, Virginia-based Kaleo, Evzio’s sponsor, . “What the harm reduction community has done as it relates to making naloxone available has been groundbreaking,” Edwards said. “It has raised awareness around overdose and it has saved lives, thousands of lives.” Evzio is not meant to be a substitute for what the harm reduction community is doing, but rather a supplement, said Edwards, adding that Kaleo is working closely with the New York -based Harm Reduction Coalition and other non-profits to make Evzio available to the harm reduction community.

Kaleo expects to launch Evzio this summer. Right now, the company is focusing on obtaining insurance reimbursement for its product and hasn’t set a price yet. “Pricing is very dependent upon each negotiation with managed care companies and pharmacy benefit companies,” said Edwards. Also planned is a patient assistance program to help people who can’t afford Evzio.

is A small company without a large sales force, Kaleo plans to target those areas where it can make the biggest difference the most quickly. “We’ll be looking at where the majority of harm is occurring with prescription opioids, and where we see an opportunity to raise awareness with pain physicians,” he said. “There are so many prescribers, and as a small company we feel it’s best to try to raise awareness where we can have the greatest impact.”

The biggest challenge is to make sure individuals know how they should use naloxone. There is no question of when naloxone should be used: Even for a suspected, but unconfirmed overdose, a family member or caregiver should administer the naloxone. But first, they have to have it in their medicine cabinet.

“When an individual receives a prescription for an opioid, and they pick it up at the pharmacy, what’s to tell them to go ahead and get a naloxone auto-injector?” Edwards asked, adding, “There’s a lot of education that needs to take place.” Included education should include risk factors for overdose such as  conditions like sleep apnea, obesity, and chronic obstructive pulmonary disease – as well as an underlying history of substance abuse.

Up until now, the focus of naloxone distribution has been on rescuing people from heroin overdoses. The problem is that five times as many people die each year from a prescription overdose as from a heroin overdose. “The greatest amount of harm is happening in the prescription arena,” said Edwards, “yet only a very small handful of programs focus on this population.”