Naloxone Model OTC Label Expected From US FDA As Part Of Opioids Strategy

US FDA Anesthetic and Analgesic Drug Products and Drug Safety and Risk Management advisory committees meet in December to discuss proposed routes to make the opioid overdose reversal agent naloxone more available: both as an OTC product and one co-prescribed with opioids.

US FDA will publish a model OTC naloxone Drug Facts label “soon” to help switch sponsors developing labeling comprehension studies and final labeling, says Commissioner Scott Gottlieb.

The agency’s work on a Drug Facts label (DFL) for naloxone reflects its encouragement to drug companies to submit Rx-to-OTC switch applications for the ingredient, one part of the agency's multi-pronged effort to find ways to help curb opioid abuse.

Gottlieb offered an update on DFLs as part of an Oct. 23 announcement of an FDA advisory committee meeting in December to discuss increasing access to naloxone, an antagonist indicated for complete or partial reversal of prescription and illicit opioid overdose, including respiratory depression.The joint meeting of the Anesthetic and Analgesic Drug Products and the Drug Safety and Risk Management Advisory Committees will consider both OTC access to naloxone and ideas for co-prescribing it with opioids.

 “We recognize the important public health opportunity to bring naloxone OTC,” Gottlieb said, noting that US opioid overdose deaths doubled to 42,249 between 2010 and 2016. He also pointed out that the agency's work on a naloxone DFL “is the first time the FDA has proactively developed this OTC framework for a drug as a way to help activate the advance of OTC products.”

FDA’s Center for Drug Evaluation and Research said May 2017 that it was developing and testing labeling to instruct consumers on administering naloxone through intramuscular injection or nasal delivery to a person experiencing an overdose. (Also see "FDA's OTC Naloxone Study Is A Starting Point For Other Switches, Not A Roadmap" - Pink Sheet, 16 May, 2017.)

"We recognize the important public health opportunity to bring naloxone OTC.” – FDA Commissioner Scott Gottlieb

Gottlieb said FDA “has made progress” on the labeling in the study, which included pictograms separate from DFL text.

In an email, an agency spokesman said FDA’s naloxone DFL is a model but each product a company develops will be unique and have different directions for use.

“Using this information, naloxone manufacturers may then be able to focus their final label comprehension testing on how well consumers understand product-specific information that has not been already tested on the model DFL,” the spokesman said. He declined to comment on whether potential sponsors for an naloxone OTC switch may be communicating currently with FDA.

However, Harm Reduction Therapeutics Inc. intends to launch the first Rx-to-OTC switch for naloxone in the US roughly between roughly March and September 2020. Michael Hufford, CEO of the Pittsburgh-based non-profit, says he is not aware of any entities other his own company who are working on a naloxone switch.

Given the severity of the overdose crisis, Hufford said in an interview that he hopes “any company with a product with naloxone is thinking of making the OTC switch.”

HRT received a $3.42m grant provided by opioid drug maker Purdue Pharma LP to fund its work on a low-cost nasal spray. (Also see "Naloxone OTC Switch Application On Horizon Thanks To $3.4M Funding From Purdue" - Pink Sheet, 6 Sep, 2018.)

Hufford says HRT is on track with its goals and is working with prescription and consumer health regulatory consultancy firm Pinney Associates as it develops and tests its label for an OTC switch. HRT plans to meet “face to face” with FDA to discuss next steps in labeling development and comprehension testing process in a couple weeks, he added. 

Beyond Emergency Responders' Use

Gottlieb said the advisory committee meeting, scheduled Dec. 17-18 at FDA’s White Oak headquarters campus in Silver Spring, Md., will help the agency develop strategies to extend use of naloxone beyond emergency responders and increase its availability in products intended for use by consumers.

“This potentially life-saving treatment is a critical tool for individuals, first responders and communities to help reduce opioid overdose deaths. We recognize that emergency treatment of known or suspected opioid overdose is an urgent public health priority. And to advance these efforts, there is still a need to improve access to naloxone,” he said.

During the meeting, FDA will ask committee members to consider options for increasing access. The advisors should weigh “logistical, economic and harm reduction aspects” of various strategies, Gottlieb said.

FDA will consider whether naloxone should be co-prescribed with “all or some” opioid prescriptions. Prescription naloxone products now available include the Evzio auto-injector marketed by kaleo Inc. and Adapt Pharma Ltd.’s Narcan Nasal Spray.

“There is the potential for significant costs and burdens that may be associated with naloxone co-prescribing,” Gottlieb said. “These include the direct economic costs to consumers and health systems. They also include practical considerations such as the need for manufacturing volume growth for naloxone and the risk of drug shortages of this product that could come from a sudden spike in prescribing.”

The committees will be asked “to consider any potential challenges to wider co-prescribing of naloxone for all or some prescription opioid patients,” FDA says.

Hufford said co-prescribing naloxone and opioids is a “reasonable” idea for helping slow the number of opioid overdose deaths. “We would love to see a co-prescription for naloxone when someone receives high-strength opioids for pain management,” he said.

In a 2017 report on stopping overdoses, the American Medical Association’s Opioid Task Force recommended co-prescribing naloxone with opioids, but said the decision should be between doctor and patient.

The Centers for Disease Control and Prevention also has recommended pairing naloxone with opioid prescription drugs “when factors that increase risk for opioid overdose, such as history of overdose, history of substance use disorder” and “higher opioid dosages” are in play.

FDA is exploring other options to tackle abuse of opioids. With recently enacted legislation granting FDA authority to mandate blister packaging, Gottlieb earlier in October announced the agency will implement unit-of-dose packaging requirements for opioid drugs. FDA plans to require immediate-release opioid pills in blister packs, limiting the amount patients can be prescribed at one time. (Also see "Opioid Blister-Pack Mandate Tops Gottlieb's Agenda With New Authority" - Pink Sheet, 21 Oct, 2018.)

Gottlieb said the December meeting will build on FDA's ongoing work to "get naloxone in the hands of people when they need it." The agency is accepting comments on the advisory committee discussions, docket FDA-2018-N-3805, through Dec. 14.

From the editors of the Tan Sheet.