Regulatory Focus™ > News Articles > US Regulators Seek Comment on WHO Proposal to Restrict Narcolepsy Drug Ingredient

US Regulators Seek Comment on WHO Proposal to Restrict Narcolepsy Drug Ingredient

Posted 08 February 2013 | By Alexander Gaffney, RAC

The US Food and Drug Administration (FDA) has announced that it is collecting comments from industry in advance of a March 2013 meeting that will decide whether gamma-Hydroxybutyric acid (GHB), an active ingredient used in at least one FDA-regulated drug product in the US and sometimes abused to commit sexual assault, should be regulated by additional sets of international restrictions.


In 1971, the US signed onto the Convention on Psychotropic Substances (CPS), which required signatories to set of substance control schemes to restrict the availability of many substances and medicines, including MDMA (ecstasy), mescaline, cathinone, methamphetamine and tetrahydrocannabinol.

In the US, the terms of the treaty were implemented through the Controlled Substances Act (CSA). Like the CPS, the CSA breaks down drug substances into four "schedules" of control, with Schedule I drugs being those without therapeutic benefit and a high potential for abuse. Schedule II drugs are those with some potential therapeutic benefits, but a high potential for abuse, while Schedules III and IV contain drugs with sequentially fewer risks associated with their drugs' respective use. The US also has a Schedule V for drugs with a low potential for abuse, an accepted medical use, but with a limited potential for physical or psychological dependence on the drug.

From time to time, the World Health Organization (WHO) conducts reviews of drug substances for possible inclusion under the CPS. In March 2013, it is set to hear arguments regarding the inclusion of gamma-Hydroxybutyric acid.

The substance is regulated in the US as a Schedule I product, though Xyrem (sodium oxybate), a narcolepsy drug derived from GHB and used to reduce cataplexy and daytime sleepiness, is FDA-approved under a Risk Evaluation and Mitigation Strategies (REMS) plan meant to heavily restrict its prescribing.

WHO Proposal

Under the WHO proposal, GHB would be significantly up-scheduled under the CPS from a Schedule IV drug to a Schedule II drug. A June 2012 report authored by WHO notes that the drug is "misused for various reasons and by various sections of society."

"These [reasons] include: its sexual enhancing effects, growth hormone promoting effects and more recently its euphoric ('high') effects," the report explained. "There have also been reports of GHB being used to facilitate sexual assault."

In light of its high potential for abuse and concerns that the drug's chemical precursors are too easily available and diverted from domestic distribution channels, the report suggested that the drug be rescheduled to Schedule II.

Under the CPS, Schedule IV drugs can only be manufactured, traded or distributed under a license, and are further restricted from certain import and export actions. Schedule II drugs are subject to the same restrictions, as well as statistical reporting requirements, prescription control measures (like REMS), tighter export restrictions and tighter laws regarding punishments for the drug's abuse.

Call for Comment

This proposal is now before the United Nations (UN) for consideration, and FDA is calling for industry and public comment regarding the position that it should advance to the secretary of state for presentation and negotiation at the UN.

It is unclear whether the schedule change would have any eventual effect on Xyrem or its manufacturer, Jazz Pharmaceuticals, since the drug is already heavily restricted.

FDA said it will be collecting comments on the proposal until 25 February 2013.

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