FDA Pushing for Over-The-Counter Sales of Naloxone

By Pat Anson, PNN Editor

The U.S. Food and Drug Administration has launched an “unprecedented” effort to support over-the-counter sales of naloxone, an overdose recovery drug credited with saving thousands of lives. The FDA has developed new drug labeling — at taxpayer expense — to encourage drug makers to start selling naloxone without a prescription.

“This is the first time the FDA has proactively developed and tested a DFL (drug facts label) for a drug to support development of an OTC product. We proactively designed, tested and validated the key labeling requirements necessary to approve an OTC version of naloxone and make it available to patients,” FDA commissioner Scott Gottlieb, MD, said in a statement.

“I personally urge companies to take notice of this pathway that the FDA has opened for them and come to the Agency with applications as soon as possible.”

FDA proposed label for evzio

Curiously, one of the labels the FDA developed would support sales of Evzio, a controversial naloxone auto-injector that sells for about $3,700.

A recent U.S. Senate report accused Kaleo – the company that makes Evzio – of inflating its price by 600% to “capitalize on the opportunity” of a “well established public health crisis.” The report estimates Medicare and Medicaid paid over $142 million in excess costs to Kaleo for its Evzio injectors.

Kaleo has since announced plans for a generic version of Evzio to be available in mid-2019 at a reduced price of $178.

The FDA has also developed an OTC label for Narcan, a naloxone nasal spray that sells for about $135.

Last month, federal health officials called naloxone an “essential element” of government efforts to reduce deaths from opioid overdoses, and urged doctors to co-prescribe naloxone to pain patients talking relatively modest doses of 50 morphine milligram equivalents (MME) or more per day.

The drumbeat for naloxone comes at a time when sales are already booming. According to the healthcare data firm IQVIA, naloxone sales grew from $21 million in 2011 to over $274 million in 2016, and are projected to reach $500 million by 2020. Many of these purchases are made through Medicare or Medicaid, or government funded grants that supply naloxone at no cost to first responders, hospitals and addiction treatment clinics. 

According to one estimate by the CDC, naloxone reversed over 26,000 opioid overdoses from 1996 to 2014, and advocates say the drug has likely prevented thousands of deaths since then.

Earlier this month, naloxone was credited with saving a dozen lives at a suspected fentanyl mass overdose that left one man dead in Chico, California.

“Without that, I’m convinced that we would have had certainly four or five, if not more, additional fatalities,” Chico Police Chief Michael O’Brien told The Los Angeles Times. “There’s no doubt it saved lives.”

Is Naloxone Increasing Opioid Abuse?

There’s no doubt naloxone saves lives, but some researchers say the drug has had little effect on the opioid epidemic and may in fact be making it worse.

In a study recently published by SSRN, an open access online journal, two economics professors said naloxone may raise the risk of an overdose by providing a “safety net” to opioid abusers -- in effect giving them a second chance to abuse more drugs. In an anlaysis of Google search results, they found anecdotal evidence that drug crimes and overdoses increased in states where there was easy access to naloxone.

“Expanding naloxone access increases opioid abuse and opioid-related crime, and does not reduce opioid-related mortality. In fact, in some areas, particularly the Midwest, expanding naloxone access has increased opioid-related mortality. Opioid-related mortality also appears to have increased in the South and most of the Northeast as a result of expanding naloxone access,” wrote Jennifer Doleac, PhD, Texas A&M University, and co-author Anita Mukherjee, PhD, University of Wisconsin.

“Our results show that broad naloxone access may be limited in its ability to reduce the epidemic’s death toll because not only does it not address the root causes of addiction, but it may exacerbate them.”

Doleac and Mukherjee say naloxone may give drug abusers a false sense of security, encouraging them to seek “a higher high” with more dangerous drugs like illicit fentanyl. The researchers said public health officials should prepare for these unintended consequences by offering addiction treatment along with naloxone.

Government-supported efforts to increase naloxone sales are not confined to the federal government. As PNN has reported, a new state law in California requires doctors to “offer” naloxone prescriptions to pain patients deemed at high risk of an opioid overdose. Nothing in the law requires patients to obtain naloxone, yet some pain sufferers say they are being “blackmailed” by pharmacists who refuse to fill their opioid scripts unless naloxone is also purchased. Patients around the country report similar experiences.   

Feds Urge Doctors to Co-Prescribe Naloxone

By Pat Anson, PNN Editor

Pain patients taking relatively modest doses of opioid medication should be co-prescribed naloxone, according to a recommendation released this week by the U.S. Department of Health and Human Services.

Naloxone is an overdose recovery drug administered by injection or nasal spray that rapidly reverses the effects of an opioid overdose. It has been credited with saving thousands of lives, although recently there has been controversy over a company exploiting demand for the drug by raising the cost of its naloxone injector over 600 percent.

“Given the scope of the opioid crisis, it’s critically important that healthcare providers and patients discuss the risks of opioids and how naloxone should be used in the event of an overdose,” said Adm. Brett Giroir, MD, assistant secretary for health and senior advisor for opioid policy at HHS.

“Co-prescribing naloxone when a patient is considered to be at high risk of an overdose, is an essential element of our national effort to reduce overdose deaths and should be practiced widely.”

But the “guidance” released by HHS could involve millions of patients who are not necessarily at high risk and have been taking opioids safely for years.  It urges doctors to “strongly consider” prescribing naloxone to patients under these circumstances:

• Patients prescribed opioids at a dose of 50 morphine milligram equivalents (MME) or more per day

• Have respiratory conditions or obstructive sleep apnea (regardless of opioid dose)

• Have been prescribed benzodiazepines (regardless of opioid dose)

• Have a mental health or non-opioid substance use disorder such as excessive alcohol use

• Are receiving treatment for opioid use disorder

• Have a history of illegal drug use or prescription opioid misuse

The HHS guidance was issued days after an FDA advisory committee voted 12 to 11 in favor of adding language to opioid warning labels recommending that naloxone be co-prescribed.  Some panel members objected to the labeling because of the additional cost involved and because it does not address deaths caused by illicit opioids, which account for the vast majority of opioid overdoses.

The guidance notes that most health insurance plans, including Medicare and Medicaid, will cover at least one form of naloxone. For patients without insurance, the guidance suggests contacting a state or local program that may supply naloxone for free or at low cost.

Naloxone costs only pennies to make and syringes containing generic versions of the drug typically cost about $15 each. But formulated and branded versions that have a more sophisticated delivery system are much pricier. According to Health Care Bluebook, a package of two nasal sprays of naloxone sold under the brand name Narcan will cost about $135.  Evzio, a kit that contains two auto-injectors of naloxone, retails for about $3,700.   

A recent U.S. Senate report found that Kaleo, a privately-owned drug maker, jacked up the price of Evzio by over 600% to “capitalize on the opportunity” of a “well established public health crisis.” As a result, the report estimates the U.S. government paid over $142 million in excess costs to Kaleo for prescriptions covered by Medicare.  

The new HHS guidance mirrors that of the 2016 CDC opioid guideline, which encourages physicians to consider prescribing naloxone to pain patients on “higher opioid dosages” of 50 MME or more.

“I’m personally against it, because I don’t think most patients who require opioids for pain management are at risk of overdose,” said Andrea Anderson, Executive Director, Alliance for the Treatment of Intractable Pain (ATIP).  “I also don’t think naloxone helps unless you’re with other people, which makes more sense for those who are using illicit opioids rather than those who rely on opioids for routine pain relief. 

“I don’t think the government should require patients to buy medications for which they do not have a proven need. This sounds like another one of those good ideas in theory but poor in practice.”

Drug Price Hiked 600% to Capitalize on Opioid Crisis

By Pat Anson, PNN Editor

A U.S. Senate report and 60 Minutes are highlighting how a Virginia drug maker exploited the opioid crisis by substantially raising the price of an overdose recovery drug and passing much of the cost to taxpayers.

The report by the Senate Subcommittee on Investigations found that Kaleo, a privately-owned pharmaceutical company, raised the price of its naloxone auto-injector Evzio by over 600% to “capitalize on the opportunity” of a “well established public health crisis.” As a result, the report estimates the U.S. government paid over $142 million in excess costs to Kaleo.

Naloxone is usually administered by injection or in a nasal spray to quickly reverse the effects of an opioid overdose. Syringes containing naloxone typically cost about $15 each, but Kaleo’s two-dose Evzio injector now sells for over $4,000. The original price was $575.

“Naloxone is a critically important overdose reversal drug that our first responders have used to save tens of thousands of lives,” subcommittee chairman Sen. Rob Portman, R-Ohio, said in a statement. “The fact that one company dramatically raised the price of its naloxone drug and cost taxpayers tens of millions of dollars in increased drug costs, all during a national opioid crisis no less, is simply outrageous.”

“We raised the price to improve access to this product,” Kaleo CEO Spencer Williamson told 60 Minutes. “The big misperception is that by raising the price of Evzio we reduce the access to this product. The exact opposite is true.”

Prescriptions for Evzio increased substantially after the price increase, but largely because Kaleo urged its sales department to have doctors sign prior authorization forms for patients stating that “Evzio was medically necessary.” Under that language, Medicare had no choice but to pay for Evzio at nearly full price.

When it was approved by the Food and Drug Administration in 2014, federal health officials called Evzio a “more user-friendly version” of naloxone because the injector gives verbal instructions on how to use it and can be administered by anyone.  Evzio was given fast-track status by the FDA and approved in less than 15 weeks without an advisory committee hearing.

“The approval of this product is great,” Andrew Kolodny, MD, founder and Executive director of Physicians for Responsible Opioid Prescribing (PROP) told Medscape at the time.

Kaleo began raising the price for Evzio the following year. By 2018, the average cost of an injector for Medicare patients was nearly $4,100. The cost for patients who pay in cash or are covered under private insurance is similar, but they make up only a fraction of Evzio sales as most insurers refuse to pay for the injectors.  As a result, Medicare and Medicaid payments account for an oversized portion of Kaleo’s revenue.

The company claims Evzio has saved over 5,500 lives since it was introduced and that “we have never turned an annual profit on the sale of Evzio.”

Naloxone has rapidly gone mainstream in recent years as public health officials and politicians have reacted to the opioid crisis by spending billions of dollars on addiction treatment and overdose prevention. Naloxone rescue kits are now routinely carried by police, firefighters and paramedics or given to heroin and opioid addicts to keep at home.

Naloxone is not usually prescribed to patients taking opioids for pain relief, although a 2016 study suggested it should be. The CDC opioid guideline also encourages physicians to prescribe naloxone to pain patients – even those on relatively modest doses.

“Providers should incorporate into the management plan strategies to mitigate risk, including considering offering naloxone when factors that increase risk for opioid overdose, such as history of overdose, history of substance use disorder, or higher opioid dosages (≥50 MME), are present,” the guideline states.

Over the years, Kaleo has donated hundreds of thousands of free Evzio injectors to first responders, schools, hospitals and addiction treatment clinics. STAT News has reported that the naloxone in many of the injectors was just months away from expiring.

According to ProPublica, in 2016 Kaleo paid nearly $950,000 to pain management doctors and addiction treatment specialists for consulting, promotional speaking, travel, lodging, and food and beverage expenses.