[Federal Register Volume 64, Number 86 (Wednesday, May 5, 1999)]
[Proposed Rules]
[Pages 24094-24095]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 99-11289]


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DEPARTMENT OF JUSTICE

Drug Enforcement Administration
[DEA-182P]

21 CFR Part 1308


Schedules of Controlled Substances: Proposed Placement of 
Zaleplon into Schedule IV

AGENCY: Drug Enforcement Administration, Department of Justice.

ACTION: Notice of proposed rulemaking.

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SUMMARY: This proposed rule is issued by the Deputy Administrator of 
the Drug Enforcement Administration (DEA) to place the substance 
zaleplon, including its salts, into Schedule IV of the Controlled 
Substances Act (CSA). This proposed action is based on a recommendation 
from the Assistant Secretary for Health and Surgeon General of the 
Department of Health and Human Services (DHHS) and on an evaluation of 
the relevant data by the DEA. If finalized, this action will impose the 
regulatory controls and criminal sanctions of Schedule IV on those who 
handle zaleplon and products containing zaleplon.

DATES: Comments, objections and requests for a hearing must be received 
on or before June 4, 1999.

ADDRESSES: Comments, objections and requests for a hearing should be 
submitted in quintuplicate to the Deputy Administrator, Drug 
Enforcement Administration, Washington, D.C. 20537; Attention: DEA 
Federal Register Representative/CCR.

FOR FURTHER INFORMATION CONTACT: Frank Sapienza, Chief, Drug and 
Chemical Evaluation Section, Drug Enforcement Administration, 
Washington, D.C. 20537, (202) 307-7183.

SUPPLEMENTARY INFORMATION: Zaleplon is a central nervous system (CNS) 
depressant that is being considered for marketing approval by the Food 
and Drug Administration (FDA), under the trade name 
SONATATM. Zaleplon is a sedative-hypnotic in the 
pyrazolopyrimidine class, chemically distinct from the benzodiazepines, 
which competitively binds to the gamma-aminobutyric acid, type A 
(GABAA, central benzodiazepine receptor. Its pharmacology, 
abuse and dependence liabilities are similar to those of the 
benzodiazepines that are currently listed in Schedule IV of the CSA. In 
clinical trials zaleplon was found to be approximately 100-times less 
potent but equivalent in its potential for abuse when compared to the 
prototypic benzodiazepine, triazolam; triazolam is in Schedule IV of 
the CSA. Zaleplon will be marketed as a prescription drug product for 
the short-term treatment of insomnia.
    Zaleplon is N-[3-(3-cyanopyrazol [1,5-alpyrimidin-7-yl]-N-
ethylacetamide, and has been identified by code names CL-284,846 and 
ZAL-846. There are no asymmetric centers in the molecule or any optical 
isomers. Zaleplon has a rapid onset and short duration of action, and 
forms no pharmacologically-active metabolite in man. Zaleplon reduces 
sleep latency but has a relatively insignificant effect on total sleep 
time. These pharmacokinetic characteristics of zaleplon should prevent 
any long-term carryover or hangover effects. However, zaleplon has 
shown a mild to moderate benzodiazepine-like withdrawal syndrome after 
acute and continuous dosing studies in baboons.
    Zaleplon has demonstrated significant muscle relaxant, ataxic, 
anticonvulsant, and anxiolytic effects and cognitive impairments in 
preclinical screening assays. Zaleplon is reinforcing in animals as 
demonstrated by self-administration studies. It produces euphoria, 
alterations in mood, perception, memory and subjective effects in 
humans typical of other benzodiazepines with abuse potential in 
Schedule IV.
    The complexity of the synthesis procedure for preparation of 
zaleplon precludes a likely synthesis of the drug substance outside a 
laboratory environment and by individuals lacking training in organic 
chemistry synthesis. Hallucinations, amnesia, depression and hostility 
were the most serious adverse events related to the use of zaleplon 
during the clinical trials. Zaleplon-related overdoes were also noted 
during the clinical trails. Zaleplon-related overdoes were also noted 
during the clinical development program. The FDA has concluded that 
zaleplon's abuse potential appears to be lower than that of Schedule II 
depressants and similar

[[Page 24095]]

to the Schedule IV benzodiazepines. On March 31, 1999, the Assistant 
Secretary for Health and Surgeon General, Department of Health and 
Human Services (DHHS), sent the Deputy Administrator of DEA a letter 
recommending that zaleplon, and its salts, be placed into Schedule IV 
of the CSA (21 U.S.C. 801 et seq.). Enclosed with the March 31, 1999, 
letter was a document prepared by the FDA entitled, ``Basis for the 
Recommendation for Control of Zaleplon in Schedule IV of the Controlled 
Substances Act (CSA).'' The document contained a review of the factors 
which the CSA requires the Secretary to consider [21 U.S.C. 811(b)].
    The correspondence from the Assistant Secretary for Health and 
Surgeon General to the DEA dated March 31, 1999, confirmed that FDA had 
determined that the New Drug Application (NDA) for zaleplon was 
``approvable'' and had issued an approvable letter to the NDA sponsor 
on January 6, 1999. According to the March 31, 1999, letter from DHHS, 
``upon full approval of the NDA, zaleplon will have a currently 
accepted medical use in treatment in the United States.''
    The factors considered by the Assistant Secretary of Health and 
Surgeon General and the DEA with respect to zaleplon were:
    (1) Its actual or relative potential for abuse;
    (2) Scientific evidence of its pharmacological effects;
    (3) The state of current scientific knowledge regarding the drug;
    (4) Its history and current pattern of abuse;
    (5) The scope, duration, and significance of abuse;
    (6) What, if any, risk there is to the public health;
    (7) Its psychic or physiological dependence liability; and
    (8) Whether the substance is an immediate precursor of a substance 
already controlled under this subchapter.

21 U.S.C. 811(c).
    Relying on the recommendation of the Assistant Secretary for Health 
and Surgeon General, received in accordance with section 201(b) of the 
Act [21 U.S.C. 811(b)], and the independent review of the available 
data by the DEA, the Deputy Administrator of the DEA, pursuant to 
sections 201(a) and 201(b) of the Act [21 U.S.C. 811(a) and 811(b)], 
find that:

    (1) Based on information now available, zaleplon has a low 
potential for abuse relative to the drugs or other substances in 
Schedule III;
    (2) Zalepon will, upon approval of an NDA by the FDA, have a 
currently accepted medical use in treatment in the United States; 
and
    (3) Abuse of zaleplon may lead to limited physical dependence or 
psychological dependence relative to the drugs or other substances 
in Schedule III.

21 U.S.C. 812(b)(4).
    Based on these findings, the Deputy Administrator of the DEA 
concludes that zaleplon, including its salts, warrants control in 
Schedule IV of the CSA, if and when the zaleplon NDA is approved by the 
FDA. It is noted that zaleplon does not have optical isomers to be 
controlled under this action.
    Interested persons are invited to submit their comments, objections 
or requests for a hearing, in writing, with regard to this proposal. 
Requests for a hearing should state, with particularity, the issues 
concerning which the person desires to be heard. All correspondence 
regarding this matter should be submitted to the Deputy Administrator, 
Drug Enforcement Administration, Washington, DC, 20537. Attention: DEA 
Federal Register Representative/CCR. In the event that comments, 
objections, or requests for a hearing raise one or more issues which 
the Deputy Administrator finds warrants a hearing, the Deputy 
Administrator shall order a public hearing by notice in the Federal 
Register, summarizing the issues to be heard and setting the time for 
the hearing.
    In accordance with the provisions of the CSA [21 U.S.C. 811(a)], 
this action is a formal rulemaking ``on the record after opportunity 
for a hearing.'' Such proceedings are conducted pursuant to the 
provisions of 5 U.S.C. 556 and 557 and, as such, are exempt from review 
by the Office of Management and Budget pursuant to Executive Order 
(E.O.) 12866, section 3(d)(1). The Deputy Administrator, in accordance 
with the Regulatory Flexibility Act [5 U.S.C. 605(b)], has reviewed 
this proposed rule and by approving it certifies that it will not have 
a significant economic impact on a substantial number of small 
entities. Zaleplon products will be prescription drugs used for the 
short-term treatment of insomnia. Handlers of zaleplon also handle 
other controlled substances used to treat insomnia which are already 
subject to the regulatory requirements of the CSA.
    This rule will not result in the expenditure by State, local and 
tribal governments, in the aggregate, or by the private sector, of 
$100,000,000 or more in any one year, and it will not significantly or 
uniquely affect small governments. Therefore, no actions were deemed 
necessary under provisions of the Unfunded Mandates Reform Act of 1995.
    This rule is not a major rule as defined by Sec. 804 of the Small 
Business Regulatory Enforcement Fairness Act of 1996. This rule will 
not result in an annual effect on the economy of $100,000,000 or more; 
a major increase in costs or prices: or significant adverse effects on 
competition, employment, investment, productivity, innovation, or on 
the ability of the United States-based companies to compete with 
foreign-based companies in domestic and export markets.
    This rule will not have substantial direct effects on the States, 
on the relationship between the national government and the States, or 
on the distribution of power and responsibilities among the various 
levels of government. Therefore, in accordance with E.O. 12612, it is 
determined that this rule, if finalized, will not have sufficient 
federalism implications to warrant the preparation of a Federalism 
Assessment.

List of Subjects in 21 CFR 1308

    Administrative practice and procedure, Drug traffic control, 
Narcotics, Prescription drugs.
    Under the authority vested in the Attorney General by section 
201(a) of the CSA [21 U.S.C. 811(a)], and delegated to the 
Administrator of the DEA by the Department of Justice regulations (28 
CFR 0.100), and redelegated to the Deputy Administrator pursuant to 28 
CFR 0.104, the Deputy Administrator hereby proposes that 21 CFR part 
1308 be amended as follows:

PART 1308--(AMENDED)

    1. The authority citation for 21 CFR part 1308 continues to read as 
follows:

    Authority: 21 U.S.C. 811, 812, 871(b) unless otherwise noted.

    2. Section 1308.14 is proposed to be amended by redesignating the 
existing paragraph (c)(48) to (c)(49) and by adding a new paragraph 
(c)(48) to read as follows:


Sec. 1308.14  Schedule IV.

* * * * *
    (c) * * *
(48) Zaleplon......................................................2781
* * * * *
    Dated: April 26, 1999.
Donnie R. Marshall,
Deputy Administrator.
[FR Doc. 99-11289 Filed 5-4-99; 8:45 am]
BILLING CODE 4410-09-M