Attorneys General Ask FDA to Rethink Zohydro ER Approval

Susan Jeffrey

December 12, 2013

The attorneys general of 29 states and territories have sent a letter to the US Food and Drug Administration (FDA) asking that the agency consider reversal of its recent approval of a single-entity extended-release hydrocodone product (Zohydro ER, Zogenix Inc).

The letter is addressed to Margaret Hamburg, MD, FDA Commissioner of Food and Drugs.

"We believe your approval of Zohydro ER has the potential to exacerbate our nation's prescription drug abuse epidemic because this drug will be the first hydrocodone-only opioid narcotic that is reportedly 5 to 10 times more potent than traditional hydrocodone products, and it has no abuse-deterrent properties," the attorneys general write.

"We hope that the FDA either reconsiders its approval of Zohydro ER, or sets a rigorous timeline for Zohydro ER to be reformulated to be abuse-deterrent while working with other federal agencies on how Zohydro ER can be marketed and prescribed," they conclude. "Law enforcement officers, public health workers, and substance abuse treatment providers are just now beginning to stem the tide of prescription drug addiction. We do not want to see their dedicated work undone."

Asked for comment, the FDA press office told Medscape Medical News that the agency is reviewing the letter and plans to respond directly to the attorneys general.

On November 1, Zogenix announced a new collaboration with Altus Formulation Inc to develop an abuse-deterrent formulation of Zohydro ER.

A "Vicious Cycle"

Zohydro ER was approved in October "for the management of pain severe enough to require daily around-the-clock long-term treatment and for which alternative options are inadequate," the FDA said in a statement at that time.

"Zohydro ER will offer prescribers an additional therapeutic option to treat pain, which is important because individual patients may respond differently to different opioids," the FDA statement said. "Due to the risks of addiction, abuse, and misuse with opioids, even at recommended doses, and because of the greater risks of overdose and death with ER/LA [extended-release/long-acting] opioid formulations, Zohydro ER should be reserved for use in patients for whom alternative treatment options are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain."

The decision to approve the product had many puzzled, both because the FDA's decision went against the recommendation of the agency's advisory panel and because of its proximity to another decision, to reschedule all other combination hydrocodone formulations, including the hydrocodone-acetaminophen combo Vicodin, from Schedule III to Schedule II, increasing security measures associated with its use in an effort to reduce misuse.

"By early December, FDA plans to submit our formal recommendation package to HHS [US Department of Health and Human Services] to reclassify hydrocodone combination products into Schedule II," Janet Woodcock, MD, director of the FDA's Center for Drug Evaluation and Research, said in a statement posted on the FDA Web site October 24.

The approval of Zohydro ER was "more shocking to me than this announcement," Edward Michna, MD, member of the American Pain Society, told Medscape Medical News at that time. That these 2 events happened back-to-back is "kind of odd," added Dr. Michna, who is director of the Pain Trials Center at Brigham and Women's Hospital and assistant professor at Harvard Medical School, both in Boston, Massachusetts.

"Zohydro is another drug that doesn't have abuse-deterrent technology; so you have another opioid in high dose that is going to be released [in the midst] of pressure on drug companies to develop abuse-deterrent drugs," Dr. Michna noted.

Signing the letter addressed to the FDA are attorneys general from Alaska, Arizona, Arkansas, Connecticut, Delaware, Florida, Georgia, Guam, Hawaii, Illinois, Indiana, Iowa, Kentucky, Maine, Maryland, Massachusetts, Michigan, Mississippi, Nevada, New Hampshire, North Carolina, Oregon, Pennsylvania, Rhode Island, South Dakota, Tennessee, Utah, Vermont, and Washington.

What they don't want, they write, is "a repeat of the recent past, when potent prescription painkilling drugs entered the market without abuse-deterrent qualities and without clear guidance on how they were to be prescribed. This created an environment whereby our nation witnessed a vicious cycle of overzealous pharmaceutical sales, doctors over-prescribing the narcotics, and patients tampering with these drugs, ultimately resulting in a nationwide prescription drug epidemic claiming thousands of lives."


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