OTC Opioid Overdose Antidote: Why is it not FDA Approved?

Regulatory NewsRegulatory News
| 24 February 2016 | By Zachary Brennan 

The case of the opioid overdose antidote naloxone (also known as Narcan) offers an interesting look at how states can offer a prescription drug without a prescription at local pharmacies, even though the US Food and Drug Administration (FDA) has not approved it as an over-the-counter drug.

Prescription opioid overdose deaths in the US are now the leading cause of injury death – surpassing motor vehicle crashes. And between 2000 and 2014, the rate of deaths from drug overdoses increased 137%, including a 200% increase in the rate of overdose deaths involving opioids, according to the CDC. But if naloxone is administered quickly, it can counter the overdose effects, usually within two minutes, according to FDA.

The use of the 45-year-old naloxone is uncontested, and President Barack Obama’s budget for 2017 includes a total request of $22 million for programs that support its use.

But the price of the off-patent drug in the US, despite being first approved by FDA in 1971, has steadily increased, from $1 per dose about a decade ago, to between $30 per dose and $45 per dose at CVS pharmacies in 14 states, though the formulations of the drug have changed and made it easier to administer.


What’s peculiar about naloxone is that it’s offered basically over-the-counter in 14 states currently. And CVS pharmacies in another 20 states in 2016 will also offer it, Mike DeAngelis, a spokesman for CVS, told Focus. The rollout comes as Sens. Joe Manchin (D-WV), Ed Markey (D-MA) took to the Senate floor to rail against FDA for its work around opioids and opioid approvals.

Similar to CVS, Walgreens pharmacies now offer naloxone over-the-counter in more than 5,800 of its nearly 8,200 stores, and earlier this month announced plans to make naloxone available without a prescription in 35 states and Washington D.C. in accordance with each state’s pharmacy regulations.

But naloxone is still not approved by FDA as an OTC drug, and that might not necessarily be bad in terms of accessibility for those that need it.

“In many states, regulations allow pharmacies to dispense naloxone without a patient having to present an individual prescription for it through standing order or collaborative practice agreements with prescribers,” DeAngelis explains.

“We dispense naloxone from our pharmacy counters. It is not sold as an over-the-counter product,” he said further. “Standing orders or collaborative practice agreements can be thought of as a blanket prescription that permits a pharmacy to dispense a medication to a patient. It’s the same mechanism under which pharmacists administer flu shots to patients without the patient needing a prescription for it.  These agreements are typically between the pharmacy (or pharmacy chain) and a single practitioner/physician/prescriber in each state.”

The push from CVS to make naloxone more available in the US comes as FDA in July 2015 noted that in order to make naloxone officially an OTC product, a new label for the drug would have to be developed and tested, particularly as OTC labels are small and may not be able to contain all of the information needed for a naloxone product, and there might be issues with insurance reimbursement. But the official designation of naloxone as an OTC product may also make it easier for patients to use because of the new labels.

The law that helped make naloxone available at pharmacies in Pennsylvania via third-party prescribing, which offers broad liability for prescribers, “resulted in dramatic increases in availability (e.g., naloxone was provided to 457 people in the first 5 months of 2015 compared to 157 in all of 2014) and in reversals (104 so far this year),” FDA said.

An FDA spokesman told Focus that as part of the agency’s opioid action plan, “FDA is currently reviewing options, including non-prescription availability, to make naloxone more accessible to treat opioid overdose.”

And the path to official OTC status is a tricky situation, partly because FDA cannot force the switch without a pharmaceutical sponsor submitting an application requesting that the drug be switched from prescription to nonprescription.

Price Hikes

But what’s different about naloxone, as opposed to other generic drugs that have been on the market for decades and remain cheap because of market competition, is that even as different versions of naloxone become more available, the price of the drug continues to rise. In that sense, the 4,000% price hike on naloxone over the last decade actually makes it more similar to Martin Shkreli's infamous price hikes on the toxoplasmosis drug Daraprim.

Amphastar Pharmaceuticals, one of the companies that offers the naxolone most frequently supplied to hospitals and emergency medical technicians across the US, said in its most recent quarterly earnings report that it’s seen its sales of the drug more than double, from $3.7 million in Q3 2014 to $10.5 million in Q3 2015 “as a result of increased unit volumes at higher average prices." Amphastar did not respond to a request for comment.

In July 2014, Kaleo, a privately held pharmaceutical company based in Virginia, also launched its naloxone auto-injector called Evzio, after FDA approval in April 2014 that was expedited and approved two months ahead of its Prescription Drug User Fee Act goal date, according to FDA.

In January 2015, Kaleo said it negotiated with the Clinton Health Matters Initiative, which is part of the Clinton Foundation, to offer the auto-injector “at a discount to colleges and universities, public safety organizations and community organizations,” though the actual price of what was negotiated was never disclosed.

FDA later approved another Amphastar competitor, Adapt Pharma’s Narcan nasal spray, the first FDA-approved nasal spray version of naloxone (and Amphastar is working on its own version of a nasal spray).

According to one account from June 2015, Evzio bought in a Boston CVS costs a total of $570 (co-pay was $70) while the nasal spray cost $20 ($8 co-pay).

In July 2015, Rep. Elijah Cummings (D-MD) sent a letter to Maryland state officials informing them that they might be over-paying for Amphastar’s naloxone as the price of the drug increased in Maryland by 111% between June 2014 and January 2015. Ohio and New York negotiated with Amphastar to get rebates of $6 per dose and additional rebates as any new price increases take effect.

That letter came just after FDA hosted a two-day public meeting on naloxone uptake, which also discussed the possibility of a new regulatory framework, known as the Nonprescription Safe Use Regulatory Expansion program (NSURE).

NSURE could allow the use of innovative technologies to help educate consumers about issues related to novel switch programs, though the agency said it will likely be several years before it is in place.

As FDA, states and pharmacies make the drug more available, what remains unclear is what will happen to the price of naloxone, particularly as new generic versions of the drug employ novel means of administration and keep competitors at bay.


© 2022 Regulatory Affairs Professionals Society.

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