BETHESDA, MD 13 February 2013—A multiyear Drug Enforcement Administration (DEA) effort to stem the abuse of hydrocodone-containing combination products received a boost in January when FDA advisers voted 19–10 in favor of reclassifying these products from Schedule III to Schedule II.
The vote followed two days of sometimes-emotional testimony, including tearful pleas from parents whose children died after becoming addicted to hydrocodone products and a presentation from DEA about the abuse, misuse, and diversion of these products.
"This decision has been very difficult," said Stephanie Crawford, associate professor and associate head of pharmacy administration at the University of Illinois at Chicago, who voted with the majority.
Crawford said she is concerned that rescheduling the drugs will make it more difficult for patients with a legitimate need for hydrocodone-containing products to obtain them. But she said her decision was based on the public health consequences of drug abuse, addiction, and death among patients who use the drug.
"There's no question this is a scourge, and we have to do something about it. Our present controls are not adequate," Crawford said.
Several advisers supported the idea that hydrocodone combination products are misclassified and should always have been in Schedule II.
The meeting. The 29 experts who voted on the rescheduling of hydrocodone included 9 regular and 20 temporary members of FDA's Drug Safety and Risk Management Advisory Committee.
The meeting itself was mandated by last year's Food and Drug Administration Safety and Innovation Act. The law requires FDA to hold a public meeting to solicit "advice and recommendations to assist in conducting a scientific and medical evaluation" of DEA's latest request to move hydrocodone combination products into Schedule II.
DEA had first asked FDA to conduct a scientific evaluation of the issue in 2004, and FDA's 2008 response to the request called for the products to remain in Schedule III. This year's meeting followed a second request from DEA, in 2009, to examine data on rescheduling.
By law, FDA was required to use the meeting to seek input from "patients, health care providers, harm prevention experts, the National Institute on Drug Abuse, the Centers for Disease Control and Prevention, and [DEA] regarding the health benefits and risks, including the potential for abuse and the impact of up-scheduling" hydrocodone combination products.
FDA's final decision about scientific and medical matters related to drug scheduling is binding on DEA, said Julie Finegan, associate chief counsel for drugs at FDA. The agency has not said when it will rule on the issues raised during the January meeting.
The problem. The Centers for Disease Control and Prevention (CDC) in 2011 declared prescription painkiller overdosage an epidemic in the United States. According to CDC, 100 Americans die each day from prescription drug overdoses, and 75% of these deaths involve opiates.
Data from IMS Health indicate that 131 million prescriptions for hydrocodone-containing prescription products were filled for 47 million patients in 2011. In contrast, 35 million prescriptions for oxycodone-containing products were filled for 15 million patients that year.
Products that contain oxycodone are in Schedule II.
Joseph Rannazzisi, deputy assistant administrator at DEA's Office of Diversion Control, said hydrocodone–acetaminophen combination products were the most frequently prescribed drugs from 2007 through 2011, followed by simvastatin and lisinopril.
Schedule II drugs are subject to tighter prescribing and handling restrictions than Schedule III drugs. For example, written prescriptions are usually required for Schedule II drugs. No refills are allowed, and patients are limited to no more than a 90-day supply of these medications.
Schedule II drugs are subject to more stringent record-keeping requirements than Schedule III drugs. These requirements apply throughout the distribution chain, not just in pharmacies.
Initial assignments to drug schedules were done legislatively through the Controlled Substances Act of 1970. The act placed single-ingredient hydrocodone products in Schedule II and hydrocodone combination products with up to 15 mg of the opiate in Schedule III.
According to FDA, 81 products containing up to 10 mg of hydrocodone in combination with acetaminophen or ibuprofen are currently marketed in the United States as analgesics. An additional 12 hydrocodone combination products are sold as cough suppressants.
The Controlled Substances Act specifies the process for making changes and additions to the schedules and assigns the responsibility for scientific and medical assessments of scheduled drugs to the Department of Health and Human Services (HHS).
Finegan said FDA acts as the HHS agent on scientific and medical issues related to the Controlled Substances Act.
One of the issues FDA evaluates is a drug's potential for abuse. Drugs in Schedule III must have a lower potential for abuse than drugs in Schedule I or II. FDA had determined in 2008 that hydrocodone combination products were less prone to abuse than Schedule II drugs.
FDA scientists reached the same conclusion during the January meeting, while DEA's analysis found that hydrocodone combination products and oxycodone products have a similar potential for abuse.
FDA Epidemiologist Catherine Dormitzer said the disagreement between the agencies arose because DEA's analysis relied on the amount of drug substance sold, in kilograms, while FDA calculated abuse potential on the basis of the total number of tablets dispensed.
Opposition. Among those who voted against moving hydrocodone combination products to Schedule II was John Mendelson, an addiction and pharmacology researcher at the California Pacific Medical Center Research Institute in San Francisco.
"There is no good single choice within this vote," Mendelson said. He predicted that moving hydrocodone combination products to Schedule II will result in "increased prescribing of other [Schedule II] drugs which may have greater abuse liability and will actually fuel, rather than reduce, an epidemic in progress."
"I also feel another likely outcome is if prescribing decreases, illicit opiate use will increase, with dire consequences," he said.
Representatives from pharmacy groups and patient-support organizations said people who rely on hydrocodone-containing products will find it more difficult to obtain them if they are moved to Schedule II, resulting in delayed or inadequate treatment of pain.
DEA's Rannazzisi acknowledged that no one knows how rescheduling hydrocodone-containing products would ultimately affect patients.
Nevertheless, he said, "we don't believe that there's going to be an issue with the patients getting those drugs."