The Drug Enforcement Administration plans to add the
sedative propofol to its roster of scheduled drugs.
The agency is circulating a proposed rule that would
classify propofol as a Schedule IV substance, putting it in the same category as
midazolam, diazepam, lorazepam
and the sleeping aid zolpidem, according to a DEA official familiar with the
decision. Schedule IV drugs “are known to produce euphoric moods as adverse
events and have histories of abuse” in the United States and abroad.
Another sedative on the list is fospropofol (Lusedra,
Eisai), which the DEA added to Schedule IV in 2009. Although the agency would
not provide a copy of the proposed rule for propofol, its statement for
fospropofol reflects concern that both drugs are subject to abuse:
“The current abuse profiles of propofol, the active
metabolite of fospropofol, indicate that propofol is abused by medical
professionals since they have access to the drug in medical facilities which
perform anesthesia, according to the Adverse Event Reporting System (AERS)
DataMart database (DHHS evaluation, 2008).”
While fospropofol is sold as an IV preparation, “after oral
administration fospropofol is active in the body. The oral activity of
fospropofol increases the likelihood of its abuse by other routes of
administration and its use to commit other crimes (e.g., date-rape),” the DEA
The DEA official, who did not want to speak for attribution,
said the agency currently is circulating the rule for review and characterized
its submission to the federal register as “imminent.” Once the proposed rule
enters the register, the public will have 60 days to comment on the measure,
after which the DEA will review the critiques and finalize the provision.
The American Society of Anesthesiologists (ASA) said it favored the proposed rule.
“The American Society of
Anesthesiologists (ASA) supports the placement of the drug propofol into
scheduled status under the Controlled Substances Act,” the group said in a Sept. 17 statement posted to its Web site. “This position was carefully developed over many years beginning
in 1992 when the first reports of recreational self-administration of propofol
appeared. While the preliminary information did not suggest an excessive
potential for abuse or addiction, a number of subsequent reports have raised
additional concerns about the drug’s abuse potential. In many of these
cases, mainly involving health care providers, propofol was found to be the
final drug used in a sequence of abuse that began with opiates or benzodiazepines
and ended (in some cases in death) with propofol.”
However, some specialists were not so enthusiastic.
Peter Papadakos, MD, director of critical care at Strong
Regional Trauma Center, in Rochester, N.Y., and professor of anesthesiology at
the University of Rochester, dismissed the proposed rule as an “overreaction to
the death of a celebrity”—alluding to the death in July 2009 of pop star
Michael Jackson from an overdose of the drug—and said it would add “lots of
headaches” to the practice of anesthesiology.
Critical care specialists in particular are likely to feel
the burden, he said, as they will be forced to account for doses administered
during continuous infusions of propofol in the intensive care unit. Dr.
Papadakos acknowledged that the DEA could have put even tighter reins on
propofol by scheduling it in a more restrictive class of medications. “It could
be worse, but still every cc will be logged,” he said.
Tricia Meyer, PharmD, MS, director of pharmacy at Scott and
White Healthcare, and assistant professor of anesthesiology at Texas A&M
College of Medicine, in Temple, said that the proposal “definitely will
place an added strain on resources.”
Because of the high volume of individual units of propofol
used in hospitals, “this [decision] will create a significant increase in
controlled substance paper work, which will also necessitate more personnel
oversight,” Dr. Meyer said.
If a hospital's policy in a given practice area “is to place all controlled
substances in a narcotics vault, then the large inventory of propofol may be
problematic with the typical space constraints in the vault,” she noted.
Dr. Meyer stressed that the
impact of the proposed ruling is not limited to the operating room. “Other
practice areas also use propofol; the ICU, for example, will present a
challenge different from the OR as far as record-keeping, because the drug is
given by continuous infusion.”
She added that the propofol situation is not unique. “We had a similar issue with thiopental
(Schedule III): specifically, how to make the agent readily available but yet
keep the agent controlled. Do we keep it in the anesthesia kit, which may not
provide adequate control? Or do we only keep it in the automated dispensing
cabinet, with better oversight and record keeping?”
Yet others praised the decision. “While I know many
anesthesiologists will be upset, it will probably save lives,” said Clifford
Gevirtz, MD, MPH, medical director of Resource Anesthesia Associates, who has
long advocated scheduling of propofol. In particular, Dr. Gevirtz said,
anesthesiologists, nurses and others who might abuse the drug would have a more
difficult time gaining access to the substance.
Drs. Papadakos and Gevirtz are members of the editorial board of Anesthesiology News.
The effort to schedule propofol comes at a time when the
drug is mired in a supply shortage that began, coincidentally, about the time
when Jackson died. The problem started with manufacturing issues at the plants of two propofol makers, Teva Pharmaceuticals and Hospira that have persisted for months. Teva announced last May that it would no
longer make the drug, citing low profitability.
A third company, APP Pharmaceuticals, maker of Diprivan, has been unaffected
by production issues but has been unable to meet demand for the drug. The FDA
has been allowing the importation of a European version of propofol, Propoven,
from APP’s German parent, Fresenius Kabi.
Dan Rosenberg, a spokesman for Hospira, said his company had
not seen the proposed rule and would not comment directly on the measure.
However, he said, “Hospira will continue to work with the DEA and FDA as they
move through the classification decision for propofol. If propofol is
classified as a Schedule IV substance, Hospira will implement the required
regulatory standards for the manufacture and distribution of our product to be
in compliance with the Schedule IV classification.”