Analysis: Is Naloxone More Than Just a Physicians’ Tool?

It is a remarkably effective treatment for opioid overdoses but available only by prescription. Some health care experts suggest expanded access would be a societal benefit.

Terry Horton, MD, was born at what’s now Christiana Hospital in Wilmington, Delaware. This is where he came when his grandfather died and when his children were born. So when he sees patients in the emergency department with every symptom of an overdose, he doesn’t think “addict.” He thinks: nephew, cousin, family friend.

Heather Boerner

It’s demoralizing to see people coming in over and over again, unable to get the full care they need, he says.

“Our staff also have family and friends who have substance-use disorders,” said Horton, chief of addiction medicine at Christiana Care Health System, which sees 93 percent of all overdoses in Delaware. “The medical staff is not in isolation. We’re part of this community.”

There is a way to keep those patients alive until affordable and accessible treatment is available, though. In 1971, the Food and Drug Administration approved injectable naloxone to reverse opioid overdoses. But naloxone provision hasn’t kept pace with the growing opioid epidemic, with 59,000 Americans dying from overdose in 2016, according to a New York Times analysis.

But states, the FDA and visionary doctors are working to make naloxone more available to those who are most likely to be present when a person overdoses — and those people aren’t physicians.

Three Formulations

Opioids can cause depressed respiration. Take too many opioids, take multiple opioids or take opioids in combination with a benzodiazepine, and you’re more likely to experience breathing that slows to a stop.

Naloxone blocks the opioid receptors in the brain to slow and stop loss of consciousness and depressed breathing, if used immediately. It isn’t addictive itself, and its side effects are minor, including injection-site pain and burning, flushing and sweating. If given erroneously, it’s said to have little physical impact.

When naloxone, a prescription drug, was first approved as Narcan, it was available only as an injection. However, times have changed. It’s still available via vials and syringes, but, in 2014, the FDA approved an EpiPen-style naloxone autoinjector designed to be carried by individuals, such as family and friends of opioid addicts. The following year, the FDA approved a nasal spray version that takes maybe 30 minutes to master, says Jeffrey Goodloe, MD, and medical director of the Medical Control Board, which leads the emergency medical system serving metropolitan Oklahoma City and Tulsa, Oklahoma.

“It’s a training laypeople can easily take,” he says. Physicians can train family members and patients themselves in its use. But it’s still a prescription drug.

Changing Status

This frustrates Corey Davis, senior attorney for the Network for Public Health Law. “Narcan is as easy to use as aspirin,” he says of its nasal spray formulation.

“If you had a pandemic flu that was killing 30,000 people a year and there were something that could reverse [it] — but it were prescription and people were literally dying because they couldn’t get it,” he says, “do you think the Food and Drug Administration would do something?”

The FDA has made some moves. It held public hearings in 2012 and 2015 on whether naloxone should be approved as an over-the-counter medication. Last year, it issued an opioid action plan, which stated, “The FDA is reviewing options, including over-the-counter availability, to make naloxone more accessible to treat opioid overdose.”

Also last year, Karen Mahoney, MD, the FDA’s deputy director of nonprescription drug products, wrote on the agency’s blog that the FDA is so interested in getting nasal-spray and self-injector naloxone approved for OTC use that it’s drafted its own mockup of a drug facts label, which is required for OTC medications but not prescription medications.

“We will continue to work with interested manufacturers and developers to further explore the best uses of naloxone for the emergency treatment of known or suspected opioid overdoses until emergency medical help arrives,” Mahoney wrote.

The FDA would still require additional studies and for manufacturers to put together the submission before it will consider it. Davis suspects that OTC naloxone may yet be years off, even with a motivated FDA.

“It’s a lengthy and expensive process, and the FDA doesn’t move quickly, period,” he says.

States to the Rescue

Still, naloxone access is increasing — thanks largely to state laws that expand who can prescribe it. Every state has made laws that expand access at least one of three potential ways: by allowing physicians to issue a “standing order” for naloxone, which allows pharmacists and other allied health professionals to prescribe it; by allowing physicians to write third-party prescriptions — for instance, to a mother whose child misuses prescription painkillers; or by passing good Samaritan laws that may protect physicians, other providers and even laypeople from prosecution for dispensing naloxone.

And it seems to be working. According to a July 2015 report from the FDA, naloxone sales to outpatient providers rose by 72 percent in five years. According to a case study based in Massachusetts, low levels of community-based naloxone implementation were associated with 7 percent reduction in overdose deaths. When the implementation was high, overdoses dropped by 18 percent.

Progress and Politics

Rachel Levine, MD, became Pennsylvania’s physician general in June 2015. In October, she wrote a prescription for naloxone — for the whole state. That’s a so-called standing order, permitted by her state’s laws.

Since issuing the order, Levine has done everything she can to spread the word — filling orders for the overdose antidote herself at a pharmacy in York, Pennsylvania, as well as touring the state in 2017, stumping for the standing order and the state’s new “warm handoff” law that seeks to create a protocol to channel people in the ED for overdose directly into treatment.

Yet some gaps remain. Goodloe in Oklahoma says paramedics there have carried naloxone since before he started in 1988. He’s getting calls from politicians, urging him to support grant applications to train urban police forces on naloxone use. But that doesn’t help people in rural areas, he says. The two- to three-minute wait for an ambulance in urban Oklahoma City grows to 23 minutes in the rural areas.

The same is true in western Pennsylvania, says Jason Herring, community health director for the Pittsburgh AIDS Task Force, which partners with a local syringe-access program to distribute naloxone to those who need it. The task force has a health care clinic used often, he says, by people alienated from regular health care by geography, sexuality or drug use.

The task force’s rural case managers drive all around this region of Appalachia, where syringe access programs are not permitted to work, carrying naloxone and educating patients on it.

In the end, though, he said it’s not enough for case man-agers or even pharmacists to offer naloxone information and training, because the stigma around substance use is so in-tense that it, itself, deters patients from asking for help.

“People don’t want to go to a pharmacy and request naloxone because they are terrified for a family member, and feel that gaze of, ‘You are wrong, you are bad,’ ” Herring says. “We see it every day. Just with HIV and STDs, we are constantly on the front lines of that. When you also add in IV drug use and those issues, it’s compounded, especially in rural areas, where you have one doctor for many miles.

“They’ve seen one doctor since they were children. They don’t want to go in there and tell that doctor that they are struggling with an addiction.”

Political Stigma

On top of medical stigma comes a shift in public policy based at least in part on social stigma.

The National Drug Control Strategy, assembled under former President Barack Obama, was removed from the White House’s website shortly after Donald Trump took office. Recently, Trump adviser Kellyanne Conway said there’s a four-letter word for drug addiction: “will.”

In Middletown, Ohio, a city official who’s worried about the cost of naloxone and the opioid epidemic in general says the solution isn’t medical care but, rather, is fear.

“I want to send a message to the world that you don’t want to come to Middletown to overdose, because someone might not come with Narcan to save your life,” councilman Dan Picard told the local newspaper, saying that refusing to take a third emergency call for an overdose might help alter behavior of drug users in his city.

Physicians Still Lead

Horton, the physician from Delaware, recently went to Washington to talk about the precarious state of the opioid epidemic and overdoses. The hearing, convened by the Senate Committee on Homeland Security and Government Affairs, sought information about limiting access to fentanyl and other synthetic opioids.

Horton described the program he’s implemented at Christiana Care. Yes, it makes naloxone available throughout the community, he told lawmakers. But it also includes a protocol to identify patients who need addiction care, whether they come in with an overdose or comorbidities such as endocarditis and spinal conditions. Then it teaches physicians how to identify withdrawal, start medically assisted therapy and then get patients into local drug treatment programs.

None of this would be possible, he told them, without the Affordable Care Act, which expanded both Medicaid and access to mental and behavioral health care.

“Naloxone is just a sliver of what the response needs to be,” he says of his testimony. “Today, [our patients] have access to treatment because of Medicaid. The expansion of these slots [in drug treatment programs] occurred in the last couple of years, based on the ability to bill Medicaid to fund services.”

When he hears the rhetoric out of Washington, he worries. “We are well-primed to address the opioid epidemic,” he said. “And it’s completely contingent upon Medicaid continuing to fund these programs.”

Heather Boerner is a freelance health care writer based in Pennsylvania. She covers health law and policy for the Physician Leadership Journal.