After FDA Authorization, Lots of Pressure to Rescind Zohydro ER Approval

Nahla RizkallahIn October 2013, the U.S. Food and Drug Administration (FDA) went against the recommendation of its own advisory committee and approved Zohydro® ER. The FDA’s Anesthetic and Analgesic Drug Advisory Committee of independent experts voted 11 to 2 to recommend against approval of Zohydro® ER due to concern of the potential for abuse because the product does not include acetaminophen.

What is Zohydro® ER? It is a Schedule II controlled substance under the Controlled Substances Act. It is the first FDA-approved single-entity extended-release hydrocodone without acetaminophen. Zohydro® ER is FDA indicated for the management of pain severe enough to require around-the-clock opioid, long-term treatment and for which alternative options are inadequate. Zohydro® ER has black box warnings all of which can cause fatal overdose: addiction potential, life-threatening respiratory depression, accidental exposure, neonatal opioid withdrawal syndrome, and interaction with alcohol.

Since the FDA approval of Zohydro® ER, several members of congress protested by sending an open letter to Health and Human Services Secretary, Kathleen Sebelius. In addition, in November, attorneys general of 29 states and territories have sent a letter to the FDA asking that the agency consider reversal of Zohydro® ER. Most recently, a petition from more than 40 consumer organizations, health care agencies, addiction treatment providers, and community-based drug and alcohol prevention programs called upon the FDA to revoke its approval of Zohydro® ER. However, despite all the sharp criticism that the FDA has received, Zohydro® ER was launched on March 3rd, 2014.

So, why all the hype? Why so much attention and objection? This decision was surprising to many because as the country is in the midst of a prescription drug abuse crisis, the FDA failed to apply its current standard and goal of requiring abuse-deterrent technology for all opioids. Zohydro® ER does not have abuse-resistant technology. It can be dissolved or injected, and the opioid will get into a person’s system all at once.

Because of this and the greater risks with a new extended release opioid, Zohydro ER® is not recommended as a first line drug in the Official Disability Guidelines (ODG). It is classified as an ‘N’ by ODG which means it requires pre-authorization. It is likely that Zohydro ER® will be paid for by Medicare through a prior authorization process where documentation is provided to support that the patient has tried and failed several other alternative narcotics. Post-marketing studies on Zohydro® ER are being required by the FDA to evaluate the risk of misuse, abuse, addiction, overdose and death.

The average wholesale price (AWP) per capsule is as follows: 10mg is $6.59, 15mg is $7.03, 20mg is $7.24, 30mg is $7.46, 40mg is $7.67, and 50mg is $8.00. The FDA approved frequency for Zohydro® ER is every twelve hours.

Generally, Zohydro® ER is expected to drive up the cost of MSAs. However, as with all other forms of treatment and prescriptions, Gould & Lamb uses varied clinical tools, such as drug management reviews, to assist with mitigation of such costs.

Future Considerations for Controlled-Release Oxycodone

Oxycodone CR is a slow release opioid narcotic currently indicated for use in moderate and moderate-to-severe pain. When initially released to the market, the indicated use was for pain management in cancer patients and for control of postoperative pain. As the use of controlled-release Oxycodone expanded, problems with addiction and abuse escalated.

In an effort to bring the use of Oxycodone CR under more effective control, H.R. 1366 cited as the “Stop Oxy Abuse Act of 2013” was introduced March 21, 2013 “to direct the Commissioner of Food and Drugs to modify the approval of any drug containing controlled-release (CR) oxycodone hydrochloride, to limit such approval to use for the relief of severe-only instead of moderate-to-severe pain, and for other purposes”. The introduction of the bill followed a petition filed by Physicians for Responsible Opioid Prescribing (PROP) calling for the FDA to modify opioid labeling such that future approval would exclude the term “moderate” from an indicated use for non-cancer pain. As such, approval for use would be limited to severe pain only within this population. However, the bill does not restrict the drug’s use to non-cancer pain but, rather, seeks to limit approval for use to “severe-only pain” for any patient population.

If H.R. 1366 passes, it will operate to remove use of the controlled-release oxycodone drugs for management of any form of moderate pain type diagnoses as an approved indication by the FDA. The prescribing of Oxycodone CR for “moderate” or “moderate-severe” pain would then be considered an “Off Label” use. Within the world of Medicare Set-Aside, provision of controlled-released Oxycodone for such diagnoses would be excluded from the plan of care. Any continued use of Oxycodone CR would require medical documentation and diagnosis of “severe” pain.