Zohydro ER: Proceed With Caution

Controversy surrounded the FDA approval of Zohydro ER^TM due to safety concerns. This powerful, long-acting new opioid lacks abuse-deterrent properties and is now on the market. Its use should be discouraged.

Zohydro ER^TM (hydrocodone bitartrate extended-release capsules) received FDA approval in October 2013, for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment, for which alternative treatment options are inadequate.92 It is the first formulation of hydrocodone as a single entity — meaning it is not combined with an analgesic such as acetaminophen — and the first extended-release hydrocodone formulation. Zohydro is in the same high-risk category as other opioid products such as OxyContin® (oxycodone extended-release tablet) and Exalgo® (hydromorphone extended-release tablet). However, unlike other extended-release opioids, Zohydro ER is not abuse-deterrent and has the potential to be crushed easily or chewed.

Controversial Approval

FDA approval came despite an 11-2 vote against approval by the FDA’s own scientific advisory panel. Due to several safety concerns, attorneys general from 28 states and more than 40 different groups and experts requested the FDA to reconsider Zohydro’s approval.^1,2 Subsequently, six other attorneys general joined in asking for approval to be reversed with a letter to the Department of Health and Human Services.³

The FDA approval was based on a 12-week study in patients with moderate-to-severe chronic lower back pain. Therefore, in addition to the safety concerns, it is unclear whether the results can be generalized to long-term opioid therapy for which the drug is approved.⁴

Abuse Potential

In November 2013, the FDA staff issued a memo warning that Zohydro is expected to be abused more than traditional hydrocodone combination products.₅ These safety concerns exist largely because Zohydro is an extended-release opioid formulation without abuse-deterrent properties. Tampering with an extended-release delivery system can lead to uncontrolled and rapid delivery of the entire contents of the product. This provides the user with a “high” and increases the likelihood for overdose and death.⁶

Because of these risks, attorneys general also called for a rigorous timeline for development of an abuse-deterrent formulation in their letter to the FDA.⁷ Meanwhile, in order to comply with FDA requirements aimed at reducing the risks for misuse, abuse, addiction, overdose and death associated with all extended-release and long-acting opioid analgesics, Zohydro’s labeling must emphasize appropriate patient selection and warn that serious safety risks exist even at recommended doses.⁸

In response to these safety concerns, Zogenix is developing an abuse-deterrent Zohydro formulation that is expected to reach the market in 2017.⁹ The new formulation will use a delivery system called Intellitab^TM, advertised as ultra-hard to resist crushing and chewing, and resistant to dissolution in alcohol.¹⁰ According to the manufacturer, crushing and adding an Intellitab formulation to a liquid produces a hard, dry matrix that avoids dose dumping and the desired “high.” However, loopholes exist even with purported abuse-deterrent formulations, as indicated by a study which concluded that 24 percent of Oxycontin abusers found a way to overcome the formulation’s abuse-deterrent safety measures.¹¹

Use in Workers’ Compensation

Extended-release or long-acting opioids are prevalent in workers’ compensation. Zohydro is expected to be prescribed for patients requiring chronic pain management, similar to what is seen with other extended-release or long-acting opioids which are prevalent in workers’ compensation. However, its use should be discouraged. While select patients may benefit from Zohydro, the risks for addiction, abuse and diversion must be carefully balanced with the expected benefits on a patient-by-patient basis.

Though Zohydro is less potent than other opioids such as Opana and Oxycontin, and may represent an appropriate step down in therapy, the lack of abuse-deterrent properties may lead certain patients to request Zohydro over other long-acting opioids. Therefore, the appropriateness and clinical rationale for choosing Zohydro should be confirmed for each patient.

Zohydro is designated as an “N” drug by the Official Disability Guidelines (ODG) and will require prior authorization in states that have adopted ODG Treatment Guidelines as mandatory. All payers are urged to require prior authorization for Zohydro and encourage prescribers to maximize use of non-opioid analgesics first.

Zohydro ER is available in 10mg, 15mg, 20mg, 30mg, 40mg, and 50mg capsules for twice daily administration. Due to the increased abuse potential, Zohydro is a Schedule II substance. Therefore, it will require a new written prescription each time the medication is needed, as refills are not allowed for Schedule II substances.