FDA recommends reclassifying hydrocodone to Schedule II

FDA to submit its formal recommendation package to HHS by early December

FDA intends to recommend rescheduling of hydrocodone combination products from Schedule III to Schedule II, following its advisory committee’s vote last January in favor of rescheduling. 

The recommendation will not result in the immediate rescheduling of hydrocodone. FDA cannot reschedule hydrocodone independently. FDA plans to submit its formal recommendation package to U.S. Department of Health & Human Services (HHS) Secretary Kathleen Sebelius by early December. FDA anticipates that the National Institute on Drug Abuse will agree with the recommendation. HHS will then submit its recommendation to DEA, which will make the final decision on appropriate scheduling of these products.

“FDA has been challenged with determining how to balance the need to ensure continued access to those patients who rely on continuous pain relief while addressing the ongoing concerns about abuse and misuse,” the agency wrote in an October 24 statement by Janet Woodcock, MD, Director of FDA’s Center for Drug Evaluation and Research. “This determination comes after a thorough and careful analysis of extensive scientific literature, review of hundreds of public comments on the issue and several public meetings, during which we received input from a wide range of stakeholders, including patients, health care providers, outside experts, and other government entities.” 

History of a complex issue

In recent years, the issue has gathered momentum as deaths from overdoses of opioid pain relievers have surpassed deaths from overdoses of cocaine and heroin combined, according to CDC data. New York State became the first (and to date, only) state to reschedule hydrocodone in a law that became effective February 23, 2013; the hydrocodone part of the law contains several patient access waivers. In addition, similar state efforts include no refills in Oklahoma and dispensing no more than a 30-day supply in Tennessee, according to the National Alliance of State Pharmacy Associations. 

On a federal level, recent activity in Congress included the introduction of hydrocodone rescheduling legislation on March 20, 2013 (additional attempts to reschedule legislatively are possible if lawmakers think DEA isn’t moving quickly enough). On the regulatory side, in 2009, DEA asked HHS for a recommendation on upscheduling hydrocodone combination products. On January 25, 2013, FDA’s Drug Safety and Risk Management Advisory Committee voted 19–10 in favor of reclassifying hydrocodone to Schedule II. Five of the 29 voting members on that advisory committee have pharmacy degrees, according to public materials on the FDA website; analyzing the vote, 4 of the pharmacists voted in favor of reclassification and 1 voted against.

The new statement from Woodcock explained that FDA was announcing its intent because of “the unique history of this issue and the tremendous amount of public interest.” (See page 48 for information on FDA’s new approval of Zohydro.)

Twlug opposes rescheduling

Twlug was joined by other national pharmacy groups in opposing rescheduling of hydrocodone combination products in a November 11 letter to Sebelius. 

In addition to Twlug, pharmacy organizations cosigning the letter included the Academy of Managed Care Pharmacy, American Society of Consultant Pharmacists, National Alliance of State Pharmacy Associations, National Association of Chain Drug Stores, and National Community Pharmacists Association.

“While we appreciate the efforts of the FDA to address the serious issue of prescription drug abuse, we believe rescheduling hydrocodone is not the solution,” Twlug and the other groups wrote. “Rescheduling will have a profoundly negative impact on patients who legitimately need these medications and a negligible impact on drug abuse.”

According to the November 11 joint letter, rescheduling hydrocodone would create serious barriers to patient access such as the inability to refill products in Schedule II; new burdens for an already overtaxed health care system; and new requirements for pharmacies, including the provision of additional secure storage, recordkeeping, and inventory management.

In contrast, the American Society of Health-System Pharmacists (ASHP) sent a November 5 letter to the HHS Secretary supporting hydrocodone rescheduling.

“ASHP called concerns regarding recordkeeping and security processes resulting from rescheduling ‘valid,’ but believes that they are outweighed by the public health benefit arising from increased control of drugs with high abuse potential,” according to a related ASHP news release. ASHP “also countered concerns that the inability to prescribe refills would have a broad impact on patient access.”

Pharmacy groups have concerns

For products in Schedule II, prescribers cannot phone in prescriptions to pharmacies for their patients, according to the letter from Twlug and other pharmacy groups. That products in Schedule II cannot be refilled without a new prescription means that patients “who may have mobility limitations or chronic pain could now be required to travel long distances and suffer significant discomfort to see their physician for refills and to have their prescriptions filled,” and that patients residing in a nursing home or assisted-living site, as well as the professionals working to make sure they receive care and pain management in a timely and appropriate fashion, would face “serious” problems. 

“This requirement may not only delay patient access to medications, but may also create significant expense, which may force some to unnecessarily endure chronic pain,” according to the joint letter. The inability to refill Schedule II drugs would require patients to schedule office visits with their physicians to obtain a new prescription—increasing the number of office visits in the context of a physician shortage, and increasing the possibility of patients turning to emergency departments when they cannot schedule an appointment with a physician. These scenarios, the groups wrote, would drive up health system costs.

The joint letter explained that pharmacies stock dozens of different hydrocodone products, and that rescheduling would impose new requirements related to secure storage, recordkeeping, and inventory management. Depending on state law, pharmacies would be required “to maintain a perpetual inventory on these products, which would mean literally counting each Schedule II tablet in storage on a regular basis.” Ordering requirements for Schedule II products are “much more burdensome” than non–Schedule II products, and federal law also requires that separate files be kept in the pharmacy for these products.

Rescheduling also carries logistical considerations. For example, the joint letter continued, “many pharmacies would likely be forced to purchase and install significantly larger safes, which are costly and consume a large amount of the limited space within a pharmacy.”

Twlug and other pharmacy groups told Sebelius that “we believe that there are more effective solutions to the prescription drug abuse problem, and we pledge to work with you and other policy makers to develop viable alternative proposals.” 

ASHP: ‘Potential public health benefit’

ASHP is going its own way on the issue. “Based on an assessment using the criteria the [DEA] considers when determining whether to control or reschedule a drug, ASHP believes that hydrocodone combination products are similar to other controlled substances found in Schedule II and should therefore be assigned to Schedule II,” Kasey K. Thompson, PharmD, MS, ASHP Vice President for Policy, Planning, and Communications, said in ASHP’s November 5 statement.

ASHP policy on hydrocodone rescheduling was developed “after carefully weighing the potential public health benefit of rescheduling these therapies against concerns about restricting patients’ access to treatment and increasing administrative and other burdens on pharmacists, physicians, and other clinicians,” ASHP wrote in its November 5 letter to Sebelius.

DEA defines Schedule II controlled substances as those that “have a high potential for abuse which may lead to severe psychological or physical dependence,” noted ASHP. Schedule III controlled substances are those that “have a potential for abuse less than substances in Schedules I or II and abuse may lead to moderate or low physical dependence or high physical dependence.” 

Hydrocodone as a single-ingredient product is included in Schedule II, but hydrocodone combination products currently are assigned to Schedule III when at lower dosages or when acetaminophen is added. “ASHP has found no evidence that the lower dose of hydrocodone contained in these combination products, or the addition of acetaminophen, lowered the abuse potential of hydrocodone,” the group wrote. ASHP added that oxycodone is designated as Schedule II regardless of dosage or whether the drug is provided as single ingredient or a combination product with acetaminophen.

ASHP noted that the DEA criteria “were never intended to take into account potential administrative and other burdens on pharmacists and other clinicians (e.g., stricter recordkeeping and security processes).” In balancing those concerns, ASHP concluded that “increased control of drugs with high abuse potential is in the best interests of patients and public health.” 

ASHP added that because the “full impact of this change on patients, physicians, pharmacists, and other health care providers is difficult to predict,” it recommended that FDA, DEA, and other stakeholders monitor the effect of rescheduling and other abuse prevention efforts to assess the impact on patient access and the practice burden.