The Zohydro ER Debate Continues - It’s Getting Painful

Zohydro ER

Generic Name: hydrocodone bitartrate extended-release capsules
Date of Approval: October 25, 2013
Company: Zogenix, Inc.
Treatment for: Chronic Pain

Zohydro ER is a schedule II opioid analgesic (painkiller) and the first approved acetaminophen-free and extended-release hydrocodone product in the U.S. Zohydro ER is marketed by San Diego-based manufacturer Zogenix. The drug is used for severe pain in patients who have a need for around-the-clock and long-term pain control, without the risk of liver damage due to excessive acetaminophen (Tylenol). According to the U.S. Food and Drug Administration (FDA), overdoses from prescription products containing acetaminophen account for almost half of all cases of acetaminophen-related liver failure in the U.S., and many of these cases result in a liver transplant or death.

Despite these advantages, on December 7, 2012, an FDA advisory committee of physician experts recommended against approval of Zohydro ER. They agreed that standards for opioid product approval should be raised in light of public health concerns of abuse, and extended-release products should include tamper-resistant or abuse-deterrent technology. Yet, on October 25, 2013, the U.S. Food and Drug Administration (FDA) approved the drug, stating “Zohydro ER will offer prescribers an additional therapeutic option to treat pain.” Indeed, the FDA is not obligated to follow an advisory committee recommendation, and they believed clinical studies had shown the drug was safe and effective. In March 2014, Zohydro ER, without tamper-resistant or abuse-deterrent technology, was launched into the U.S. prescription drug market. It is important to note that most approved opioids on the market today do not have abuse-resistant formulations, either.

Since approval, consumer advocacy groups, governmental authorities, law enforcement and many healthcare providers have loudly expressed concern over the FDA action on Zohydro ER. Massachusetts Governor Deval Patrick, stating worry over widespread prescription drug abuse, overdose and deaths in his state, attempted to ban. Twenty-nine state attorneys general, and multiple citizen advocacy groups have requested the FDA reverse their approval of Zohydro ER. In Vermont, Governor Peter Shumlin introduced restrictions to make it harder for doctors to prescribe the drug within state limits, although he did not institute an outright ban.

In rebuttal, Zogenix Inc., the manufacturer of Zohydro ER, filed a lawsuit on April 7th in the state of Massachusetts requesting a temporary restraining order to overturn the ban. The suit argues that the order was in direct conflict with FDA authority to determine whether a drug is safe and effective and is in direct violation of the U.S. Constitution. On Monday, April 14th, U.S. District Court Judge Rya Zobel heard arguments from both sides but abstained from making a final decision. It is believed this is the first time a state has tried to ban a drug approved by the FDA. On Tuesday, April 15th, a final decision was made and the U.S. District Court in Massachusetts entered an order preventing the implementation of the Zohydro ER ban on constitutional grounds. The federal court order takes effect on April 22.

In addition, Zogenix is hoping to clarify what it calls “rampant misinformation” by publishing Let's Get the Facts Straight About Zohydro ER - and the Important Patient Need It Fills. The release is filled with drug-specific Zohydro ER details, educational initiatives, and comparisons with other opioids.

According to Zogenix, much of the confusion with Zohydro ER lies in understanding its potency and extended-release formulation. Zohydro ER is equally as potent as oxycodone (the active ingredient in Oxycontin), but less potent than other common narcotic painkillers on the market, including oxymorphone, hydromorphone and fentanyl. Added confusion lies in the strengths of Zohydro ER, which range from 10 to 50 milligrams (mg) in an extended-release form. Zohydro is given every 12 hours, not every 4 to 6 hours like other immediate-release hydrocodone products such as Vicodin or Lortab. Thus, more hydrocodone per pill is included, and it is released more slowly over a 12-hour period. For example, a patient taking Vicodin 10 mg every 4 hours will have the same total daily dose of hydrocodone as someone taking Zohydro ER 30 mg every 12 hours.

Although Zogenix has announced plans to develop an abuse-deterrent formulation of Zohydro ER, its availability may be several years away. In fact, experts have noted that current abuse-deterrent technology lacks any true effectiveness. Instead, Zogenix is providing access to free locking pill bottle caps and discounted safe-storage units to help prevent others from obtaining unauthorized access to Zohydro ER. In addition, the company states it is committed to detecting patterns of abuse by engaging an External Safe Use Board, who will independently monitor for abuse patterns by patients, pharmacists or physicians, and report this data to the FDA. The FDA is also requiring postmarketing studies of Zohydro ER to assess risks such as misuse, abuse, overdose, and death associated with long-term use beyond 12 weeks.

Of course, none of this makes Zohydro ER, or many other long-acting opioids, any safer in the hands of a drug addict who crushes and snorts an entire capsule, or a curious toddler who mistakes the drug for candy. According to FDA commissioner Dr. Margaret Hamburg, in 2010 an estimated 16,651 people died because of abuse and misuse of opioid drugs, a 300 percent increase over the previous decade. All narcotic painkillers are strong, potentially lethal medications, and their use, storage and disposal should not be taken lightly. In the 2011 National Survey on Drug Use and Health, roughly 70 percent of respondents stated they obtained the pain relievers they abuse either for free, or by buying or taking from a friend or relative. Physicians who prescribe these medications and patients who receive them should consider the household impact of opioid drugs.

  • All medications, including potent opioids, should be kept far away from children, pets and others who may accidentally ingest the medicine.
  • Consider if there are members of the household, or their friends, who would want to gain access to narcotics for abuse or reselling purposes.
  • Think about having locked areas for storage and keeping an inventory.
  • Don’t share prescription pain relievers with others, it could be lethal.

Opioid prescription medications will remain important treatments for pain control, and healthcare providers and consumers should be proactive in safety education. The FDA has instituted the “ER/LA Opioid Analgesics Risk Evaluation and Mitigation Strategy (REMS)” for extended-release (ER) and long-acting (LA) painkillers like Zohydro ER. This plan, updated in September 2013, is designed to ensure that health care professionals are trained on how to properly prescribe opioids and how to instruct their patients about using them safely. In addition, this month local communities will team up with law enforcement to host the eighth National Prescription Drug Take-Back Day sponsored by the Drug Enforcement Agency (DEA). The “Drug Take-Back” initiative, which occurs every 6 months, aims to reduce the prescription drug abuse epidemic occurring in the U.S by allowing the public to bring expired medications or unused drugs for safe disposal, with no questions asked.

Last updated: 2014-04-16 by Leigh Anderson, PharmD.