FDA Advisory Committee Votes 19 to 10 In Favor of Rescheduling Combination Hydrocodone

By Delia A. Stubbs –

Last Friday, January 25, 2012, after two days of discussion and deliberation, an FDA Advisory Committee voted 19 to 10 in favor of rescheduling combination hydrocodone from its current placement in Schedule III to Schedule II.

The decision was informed by presentations from various perspectives, including high ranking government officials from FDA and DEA, professional societies, practitioners, industry representatives, and family members who lost loved ones to prescription drug abuse.  What began as a conversation about abuse-ratios (FDA and DEA had competing views), soon developed into a conference about prescription drug abuse generally; the practical impact of rescheduling on prescribing practices, patient access, drug distribution, opioid abuse and misuse; and alternatives to rescheduling that  would equally or more effectively reduce hydrocodone misuse and abuse.

Industry representatives argued that up-scheduling hydrocodone would impose huge costs on pharmacies, distributors, and patients with no discernible reduction on abuse and diversion.  While some committee members gave little weight to these increased costs, they also shared a concern about the change’s overall effectiveness, noting the widespread abuse of opioids currently placed in Schedule II.  Patient representatives remarked that rescheduling would increase patient (and payer) costs and impede patient access because Schedule II controlled substances, versus Schedule III controlled substances, may not be refilled.  Thus, patients who currently see their physicians twice-a-year would be required to do so as often as once a month.  To avoid the need for monthly visits, they explained, prescribers may react by increasing prescription volume, which, in turn, raises the risks of abuse and diversion, by increasing the number of pills available inside the home.

Advocating for the change from Schedule III to II, DEA Deputy Assistant Administrator, Joseph Rannazzisi, argued that tightening security and control of combination hydrocodone products by pharmacies and distributors, and increasing DEA’s enforcement tools, would reduce abuse and diversion of combination hydrocodone.  See DEA Slides, here.  He argued that many individuals start abusing combination hydrocodone due to its ease of availability, build a tolerance, and consequently move on to stronger opioids such as oxycodone and heroin.  However, he recognized that, “I am not going to be able to provide you with clear evidence [that rescheduling will work to reduce prescription opioid abuse] because there is no clear evidence until the drug actually gets rescheduled.”  In response to patient access concerns, he asked, “Is it really that bad to have to see a patient every 3 months?,” and identified a rule DEA promulgated in 2008 that allows prescribers to issue up to three post-dated 30-day prescriptions for the same Schedule II substance at one time.  He recognized, however, that many prescribers do not avail themselves of the rule.

The Committee discussed other activities that might address misuse and diversion of hydrocodone, including interoperable Prescription Drug Monitoring Programs, drug disposal initiatives, provider and patient education, and Risk Evaluation and Mitigation Strategies (“REMS”).  One Committee member who voted in favor of rescheduling stated that placing hydrocodone combination products in Schedule II is the best way to educate providers on the drug’s abuse potential.

Overall, in recommending rescheduling, many Committee members were persuaded by evidence showing combination hydrocodone acts similar to other Schedule II controlled substances, such as morphine and oxycodone.  Sharon Walsh, Ph.D., from the Center on Drug and Alcohol Research, University of Kentucky, presented evidence from human studies showing no significant difference between combination hydrocodone and combination oxycodone drugs on pupil diameter and drug “likeability.”  See S. Walsh Slides, here.  When asked by committee members for her opinion as to whether there was a meaningful difference in those drugs’ abuse potential, she opined that the drugs’ abuse potential was indeed the same.  Many Committee members later referenced Ms. Walsh’s presentation when casting their vote in favor of rescheduling.

The Advisory Committee’s recommendation is not binding on FDA and there is no statutory time-limit on when FDA must respond to DEA’s request for a scheduling recommendation.  Because there is a pending petition before DEA to reschedule these drugs, when FDA provides its recommendation to DEA, DEA will then likely proceed with a notice and comment rulemaking proposing to reschedule the drug.