Controversy surrounds FDA approval of Zohydro

Single-ingredient opioid product approved without abuse-deterrent features

On October 25, FDA approved hydrocodone bitartrate extended-release capsules (Zohydro ER—Zogenix), a single-ingredient opioid product with no abuse-deterrent features. The decision to approve Zohydro ER without such controls goes against the 2012 recommendation of the agency’s own advisory committee and came just a day after FDA announced its intent to recommend that DEA move combination hydrocodone products from Schedule III to Schedule II (see page 72).

“I was surprised FDA approved this agent despite the advisory panel recommendations,” said Chris Herndon, PharmD, BCPS, CPE, Associate Professor at Southern Illinois University Edwardsville and guest editor of Pharmacy Today’s September 2013 special section on pain. While noting that he believes that “any additional treatment options that we have available for our patients in pain are a good thing,” Herndon added, “I personally would not recommend placing this medication into the community via prescribing until it is available with an abuse-deterrent formulation.”

Why no abuse-deterrent properties?

Abuse-deterrent formulations of opioid products take a number of approaches to prevent abuse by those seeking drug highs while maintaining efficacy for patients using the products for legitimate medical needs, Eric Lavonas, MD, told the annual meeting of the RADARS System earlier this year. Such approaches include addition of naloxone, compounds such as niacin, or other substances that cause adverse effects when injected or snorted but that are pharmacologically inert when absorbed from the gastrointestinal tract. Lavonas is Associate Director of the Rocky Mountain Poison and Drug Center in Denver and Associate Professor at the University of Colorado School of Medicine. Some products are prodrugs requiring hepatic or other activation, Lavonas said. Solid oral dosage forms can also include fillers that prevent a user from getting the active drug into the body quickly through snorting or injecting and thereby achieve a heroin-like high.

In January 2013, FDA released draft guidance to assist manufacturers in developing abuse-deterrent opioids, 1 month after Zogenix presented Zohydro ER to the FDA advisory committee that advised against approval. On April 15—the day the patent for the original OxyContin was expiring—FDA approved new labeling for Purdue Pharma’s 2010 reformulation of OxyContin and also rescinded its approval of the original OxyContin. This action had the effect of preventing generic pharmaceutical companies from getting generic copies of the non-abuse-deterrent version of OxyContin approved by FDA.

When announcing FDA’s April action, Purdue Pharma said in a news release that it was working on a once-daily formulation of hydrocodone bitartrate that is “in the final stages of clinical development and incorporates the same abuse-deterrence technology as reformulated OxyContin.”

FDA considers the development of opioid analgesics with abuse-deterrent properties to be a public health priority and is actively supporting product development in this area, FDA spokesperson Eric Pahon told Today when asked why the agency would send mixed signals on this important public health issue. The science is still in its early stages, he added, and abuse-deterrent formulations are not available for most extended-release/long-acting [ER/LA] analgesics. “Accordingly, FDA does not believe it is feasible at this time to require that all new solid oral dosage form opioids have abuse-deterrent properties,” Pahon said. 

Safety in labeling

Zohydro ER is the first opioid to include FDA’s updated labeling requirements for all ER/LA opioid analgesics. In addition, FDA approved Zohydro ER with a Risk Evaluation and Mitigation Strategy (REMS). The program requires health professionals to provide Medication Guides with each prescription and counsel patients on safe use, storage, and disposal. Zohydro  also will be subject to the new postmarketing study requirements to evaluate its serious risks, including the risk of abuse with long-term use (past 12 weeks).

Before Zohydro ER’s approval, no single-entity or ER hydrocodone-containing products were available to patients. Prescribers may titrate Zohydro ER for individual patients without the limitations or toxicity concerns associated with nonopioid active ingredients, such as acetaminophen, in other approved hydrocodone products.

With the updated labeling, REMS, and postmarketing study requirements, prescribers will better understand the risks of prescribing ER/LA opioid analgesics and will be better able to determine the patients who really need them, according to FDA. When there are no indications of abuse and a patient’s pain is severe enough to require daily, around-the-clock, long-term opioid treatment, Zohydro ER provides an additional opioid option.

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