Combination Hydrocodone Products Moving to Schedule II in October


Rescheduling hydrocodone combination products to the more-restrictive schedule II will impact clinicians and patients suffering with chronic pain, but will it have the desired effect on the misuse and abuse of these products?

Hydrocodone combination products (HCPs), opioid analgesics containing other non-opioid constituents, will all become DEA schedule II agents on October 6, 2014. The “exception” that allowed HCPs formulated with acetaminophen or ibuprofen to be schedule III will end. This change means that there will be no more “called in” prescriptions allowed for any HCPs; all prescribing of these medications will be limited to written form, and for no longer 90 days, as with all other schedule II opioid analgesics.

Since the enactment of the Controlled Substances Act (CSA) in 1971, hydrocodone was listed as a schedule II agent, except when formulated with specified amounts of an isoquinoline alkaloid of opium or one or more therapeutically active non-narcotic ingredients. Zohydro, a single-entity formulation of hydrocodone, was schedule II from its launch in October 2013, consistent with the intent of the CSA.

This change of scheduling has been long expected, so it should not surprise any practitioner. In January 2013, the FDA held a public Drug Safety and Risk Management Advisory Committee (DSaRM) meeting, at which DSaRM Committee members voted 19 to 10 in favor of recommending that HCPs be placed into schedule II.

The US Department of Health and Human Services in December 2013 submitted to the DEA its scientific and medical evaluation titled, “Basis for the Recommendation to Place Hydrocodone Combination Products in Schedule II of the Controlled Substances Act.” Based upon comments received during the open public hearing and the discussion of the DSaRM members, HHS opined that (1) individuals are taking HCPs in amounts sufficient to create a hazard to their health or to the safety of other individuals or to the community; (2) there is significant diversion of HCPs; and (3) individuals are taking HCPs on their own initiative rather than on the basis of medical advice from a practitioner licensed by law to administer such drugs.

The DEA published a notice of proposed rulemaking (NPRM) in the Federal Register, titled “Schedules of Controlled Substances: Rescheduling of Hydrocodone Combination Products from Schedule III to Schedule II” proposing to reschedule HCPs from schedule III to schedule II. There was an opportunity for interested persons to file a request for hearing in accordance with DEA regulations by March 31, 2014; however, no requests for such a hearing were received. The NPRM provided an opportunity to submit written comments on the proposal by April 28, 2014. The DEA received 573 comments. Fifty-two percent (298 comments) supported, or supported with qualification, the change of HCPs to schedule II; forty-one percent (235 comments) opposed rescheduling HCPs into schedule II; seven percent (40 comments) did not take a definitive position regarding rescheduling.

Comments in opposition involved: (1) concerns over the DEA's authority to reschedule HCPs; (2) concerns over prescribing practices; (3) concerns regarding patient access to medicine; (4) concerns regarding impacts at Long-term Care Facilities (LTCFs); (5) concerns that rescheduling HCPs will not prevent abuse or diversion; (6) concerns that rescheduling HCPs will increase provider and pharmacist workload; (7) concerns regarding economic impacts to manufacturers, distributors, pharmacies, physicians, and ultimate users; (8) concerns that alternatives to rescheduling had not been explored and/or implemented first; and (9) concerns about the amount of time to comply with the rule.

Comments in support involved: the high abuse and addiction potential of HCPs, the need to curb the prescription drug abuse epidemic, preventing highly addictive drugs from getting into the wrong hands and devastating families and communities, less than thoughtful prescribing of HCPs, improper (if any) disposal of HCPs, and the lack of substantial difference between hydrocodone and other available schedule II opioids.

Prescribers should step back for a moment and ask themselves a couple of questions:

  • Will scheduling HCPs into Schedule II alone reduce opioid-related deaths, substantial opioid-abuse, misuse, or diversion?
  • If schedule II agents are prescribed less will those with “risk” for abuse still be able to obtain, misuse, overdose or die?

Alone, this will be one component of an overall strategy. This will not be a “magic bullet” that solves the entire problem of the “opioid epidemic.” Reformulating opioids to resist the usual means of manipulation, converting them from controlled-release to immediate-release to make alternative routes of administration unlikely, and combining them with sufficient amounts of opioid antagonists to block opioid agonism when used inappropriately will make a far greater impact.

We have been dealing with the abuse of schedule II opioids for more than the past decade; these were always drugs of abuse for those inclined to abuse them. OxyContin from its beginning was schedule II and it was abused. Making HCPs schedule II will not stop them from being abused, but it will hopefully limit the supply on the street. It is not the schedule that really matters. It is the decision-making process of the prescriber. If patients are properly evaluated, carefully started on opioid therapy, followed closely through time, and opioid trials are actually “trials” with defined end-points and exit-strategies, then the abuse, misuse, overdose and death associated with their use can be reduced. Criminal diversion will still occur, because criminals actually commit crimes.

I hope that classifying HCPs as schedule II agents makes a significant difference. I hope that over the next few months more prescribers will obtain opioid prescribing education (consistent with the intent of the opioid REMS initiatives). I hope that all opioids (immediate- and controlled-release versions) will be formulated to resist the usual means of manipulation used for intoxication instead of therapeutic benefit. I hope more people will properly dispose of unused opioids. I hope that public education for consumers will heighten their willingness to manage opioid therapy more successfully. I hope that more Americans will have access to substance abuse services if needed. I hope that people in pain will still have access to opioid therapy if needed. I truly hope that this next “experiment” turns the tide of the “opioid epidemic.”

What do you think? Send your comments to

B. Eliot Cole, MD, MPA, is a member of the Pain Management editorial advisory board. He has served in executive positions for several prominent pain management organizations and societies, including the American Society of Pain Educators and the American Academy of Pain Management. He has been a pain management fellow, clinician, educator, and advocate for nearly 30 years and has practiced in a variety of settings serving a wide range of patients.

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