FDA Releases its Briefing Concerning Rescheduling of Hydrocodone Combination Products in Advance of Advisory Committee Meeting

By Karla L. Palmer & Delia A. Stubbs –

As previously reported, FDA scheduled an advisory committee meeting (“ADCOM”) to take place on October 29th and October 30th to take public comments on the potential rescheduling of combination hydrocodone products from Schedule III to Schedule II.  (Because of Hurricane Sandy, the meeting has been postponed to a later date.)  The committee meeting stems from Congress’s requirement pursuant to the recently passed Food and Drug Administration Innovation Safety Act (“FDASIA”) that FDA convene a meeting “to solicit advice and recommendations to assist in conducting a scientific and medical evaluation” on whether to reschedule combination drug products containing hydrocodone.  77 Fed. Reg. 34,051 (June 8, 2012); FDASIA, Pub. L. No. 112-144, 126 Stat. 993, § 1139(a) (2012). 

FDA published a briefing document Thursday, October 25, 2012, that informs interested parties of some of the core issues that will be discussed during that meeting and which in some respects forecasts FDA’s position on the rescheduling issue.  The briefing states that in 2004, DEA requested that the Secretary of HHS make a scientific and medical evaluation and rescheduling recommendation for combination hydrocodone products.  FDA Briefing Document, Drug Safety and Risk Management Advisory Committee (DSaRM) Meeting 1, 5 (Oct. 2, 2012).  In 2008, FDA fulfilled that request, and recommended that DEA not reschedule the drug.  Id. at 6.  DEA renewed its request in 2009, submitting new data to FDA’s Center for Drug Evaluation and Research.  Id.  FDA states that its October 2, 2012 briefing is in response to, and a re-evaluation of data concerning, that 2009 request. 

FDA’s latest briefing at least suggests that FDA is not readily inclined to change its earlier position to leave hydrocodone products in Schedule III.  FDA acknowledges that single entity hydrocodone is classified in Schedule II, and that substances are scheduled under the Controlled Substances Act according to their abuse potential.  However, FDA also recognized the important role served by Schedule III combination hydrocodone products such as antitussive/cough suppressants, and it detailed their use in the effective medical treatment of pain (as demonstrated by their widespread availability).  Id. at 7-8.  Further, while FDA recognized that a review of scientific literature showed that combination hydrocodone products produce abuse-related effects similar to those of the typical Schedule II mu-opioid agonists, it emphasized that those effects are “dose related,” and are “only observed in doses of hydrocodone bitartrate equal to or greater than 15 mg when taken orally.”  Id. at 16-17.  The briefing noted that “currently the highest strength of hydrocodone combination products is of 10mg,” although combination products containing as much as 15 mg of hydrocodone are permissible.  Id. at 17.  Moreover, after explaining its rationale behind the best measure of actual abuse of combination hydrocodone products (FDA considered Drug Abuse Warning Network data that collects a nationally representative sample of emergency department visits and total number of extended units dispensed), FDA concluded that “there is insufficient evidence to support DEA’s finding that combination hydrocodone-containing products have a similar potential for abuse to oxycodone products.”  Id. at 24.   

The briefing goes on to describe the effects of hydrocodone combination product rescheduling on clinical access.  It explains that hydrocodone combination products would no longer be available for prescription by mid level practitioners such as nurses, physicians, and optometrists, who are not authorized in some states to prescribe Schedule II controlled substances.  This finding is consistent with several public comments written by practitioners that uniformly support a decision by FDA not to recommend rescheduling. See Drug Safety and Risk Management Advisory Committee Notice, Comments, FDA-2012-N-0548.

In its conclusion, FDA left the ultimate issue open.  It stated, “[o]verall a scientific and comprehensive evaluation of the relative abuse potential of hydrocodone combination products needs to be weighed in the final recommendation” of whether to reschedule the drug.  Id. at 27.  It further stated, “[t]he question that still remains is how to reduce the levels of abuse of hydrocodone combination products.  Alternatives to up-scheduling may also decrease the levels of abuse and misuse of these products and may prove beneficial and effective in addressing abuse and misuse of hydrocodone combination products.”  Alternatives mentioned by FDA include Prescription Drug Monitoring Programs and increased educational efforts.  Id.

We will update this post with the date, time and place of the rescheduled ADCOM meeting on rescheduling hydrocodone combination products.