[Federal Register Volume 68, Number 22 (Monday, February 3, 2003)]
[Notices]
[Pages 5295-5296]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 03-2456]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. 03N-0015]
International Drug Scheduling; Convention on Psychotropic
Substances; Single Convention on Narcotic Drugs; World Health
Organization Scheduling Recommendation for Amineptine (7-[(10,11-
dihydro-5H-dibenzo[a,d]cyclohepten-5-yl)amino]heptanoic acid)
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice.
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SUMMARY: The Food and Drug Administration (FDA) is providing interested
persons with the opportunity to submit written comments concerning a
recommendation by the World Health Organization (WHO) to impose
international manufacturing and distribution restrictions, under
international treaties, on a drug substance. The comments received in
response to this notice will be considered in preparing the U.S.
position on this proposal for a meeting of the United Nations
Commission on Narcotic Drugs (CND) in Vienna, Austria, April 8 to 17,
2003. This notice is issued under the Controlled Substances Act.
DATES: Submit written or electronic comments by March 1, 2003.
ADDRESSES: Submit written comments to the Dockets Management Branch
(HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061,
Rockville, MD 20852. To ensure expeditious review of written comments,
send a copy by facsimile or e-mail to: James R. Hunter (see following
address).
FOR FURTHER INFORMATION CONTACT: James R. Hunter, Controlled Substances
Staff (HFD-9) Food and Drug Administration, 5600 Fishers Lane,
Rockville, MD 20857, 301-827-2098, FAX: 301-443-9222, e-mail:
[email protected].
SUPPLEMENTARY INFORMATION:
I. Background
The United States is a party to the 1971 Convention on Psychotropic
Substances (the Convention). Section 201(d)(2)(B) of the Controlled
Substances Act (the CSA) (21 U.S.C. 811(d)(2)(B)) provides that when
the United States is notified under Article 2 of the Convention that
CND proposes to decide whether to add a drug or other substance to one
of the schedules of the Convention, transfer a drug or substance from
one schedule to another, or delete it from the schedules, the Secretary
of State must transmit notice of such information to the Secretary of
Health and Human Services (HHS). The Secretary of HHS must then publish
a summary of such information in the Federal Register and provide
opportunity for interested persons to submit comments. The Secretary of
HHS must then evaluate the proposal and furnish a recommendation to the
Secretary of State that shall be binding on the representative of the
United States in discussions and negotiations relating to the proposal.
As detailed in the following paragraphs, the Secretary of State has
received notification from the Secretary-General of the United Nations
(the Secretary-General) regarding a substance to be considered for
control under the Convention. This notification reflects the
recommendation from the 33d WHO Expert Committee for Drug Dependence
(ECDD), which met September 14 to 16, 2002. In the Federal Register of
April 9, 2002 (67 FR 17074), FDA announced the WHO ECDD review and
invited interested persons to submit information for WHO's
consideration.
The full text of the notification from the Secretary-General is
provided in section II of this document. Section 201(d)(2)(B) of the
CSA requires the Secretary of HHS, after receiving a notification
proposing scheduling, to publish a notice in the Federal Register to
provide the opportunity for interested persons to submit information
and comments on the proposed scheduling action.
II. United Nations Notification
The formal United Nations notification that identifies the drug
substance and explains the basis for the recommendation is reproduced
below.
Notification on amineptine: Reference: NAR/CL.12/2002 CS18/02 CU
2002/262.
The Secretary-General of the United Nations presents his
compliments to the Secretary of State of the United States of
America and has the honour to inform the Government that the World
Health Organization (WHO), pursuant to article 2, paragraphs 1 and 4
of the Convention on Psychotropic Substances, 1971, has notified him
that it is of the opinion that amineptine should be placed in
Schedule II of that Convention.
Article 2, paragraphs 1 and 4, of the Convention read:``
1. If a Party or the World Health Organization has information
relating to a substance not yet under international control which in
its opinion may require the addition of that substance to any of the
Schedules of this Convention, it shall notify the Secretary-General
and furnish him with the information in support of that
notification. The foregoing procedure shall also apply when a Party
or the World Health Organization has information justifying the
transfer of a substance from one Schedule to another among those
Schedules, or the deletion of a substance from the Schedules.''
``4. If the World Health Organization finds: (a) That the
substance has the capacity to produce (i)(1) a state of dependence,
and (2) central nervous system stimulation or depression, resulting
in hallucinations or disturbances in motor function or thinking or
behaviour or perception or mood, or (ii) similar abuse and similar
ill effects as a substance in Schedule I, II, III or IV, and (b)
That there is sufficient evidence that the substance is being or is
likely to be abused so as to constitute a public health and social
problem warranting the placing of the substance under international
control, the World Health Organization shall communicate to the
Commission an assessment of the substance, including the extent or
likelihood of abuse, the degree of seriousness of the public health
and social problem and the degree of usefulness of the substance in
medical therapy, together with recommendations on control measures,
if any, that would be appropriate in the light of its assessment.''
In accordance with the provisions of article 2, paragraph 2, of
the 1971 Convention, the Secretary-General hereby transmits the text
of that notification as an annex to the present note. The
notification together with the assessments and recommendations from
WHO as well as any data received from governments on that substance,
will also be brought to the attention of the Commission
[[Page 5296]]
on Narcotic Drugs at its forty-sixth session in April 2003.
Any decision taken by the Commission with respect to that
notification, pursuant to article 2, paragraph 5 of the Convention,
will be notified to States Parties in due course.
Article 2, paragraph 5, of the Convention reads:
``The Commission, taking into account the communication from the
World Health Organization, whose assessments shall be determinative
as to medical and scientific matters, and bearing in mind the
economic, social, legal, administrative and other factors it may
consider relevant, may add the substance to Schedule I, II, III or
IV. The Commission may seek further information from the World
Health Organization or from other appropriate sources.''
The Secretary-General would appreciate it if the Government
would submit data on seizures of amineptine or on the existence of
clandestine laboratories manufacturing it, as well as any economic,
social, administrative or other factors the Government may consider
relevant to the question of the possible scheduling of amineptine by
the Commission.
The Secretary-General would also appreciate it if the requested
information could be communicated by 30 January 2003 to the
Secretary, Commission on Narcotic Drugs, P.O. Box 500, A-1400
Vienna, Austria, fax: +43-1-26060-5885.
20 December 2002
NAR/CL.12/2002
Annex--Note Addressed to the United Nations by the World Health
Organization
The World Health Organization presents its compliments to the
United Nations and has the honour to submit, in accordance with
article 2, paragraphs 1 and 4 of the Convention on Psychotropic
Substances, 1971, assessments and recommendations of the World
Health Organization, as set forth in the annex hereto, concerning
the proposed placement of amineptine in Schedule II of the 1971
Convention.
The World Health Organization avails itself of this opportunity
to present to the United Nations the assurance of its highest
consideration.
AMINEPTINE (INN)
Substance identification
Amineptine (7-[(10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-
yl)amino]heptanoic acid) is available as either the free base (CAS
57574-09-1) or as the hydrochloride salt (CAS 30272-08-3). There are
no chiral carbon atoms; therefore, no stereoisomers or racemates are
possible.
Similarity to known substances and effects on the central
nervous system
Amineptine is a synthetic, atypical tricyclic antidepressant
with central nervous system stimulating effects. It is an indirect
dopamine agonist, selectively inhibiting dopamine uptake and
inducing dopamine release, with additional stimulation of the
adrenergic system. Its antidepressant effects are similar to other
tricyclic antidepressant drugs but it has a more rapid action, is
better tolerated and has little cardiovascular, analgesic or
anorectic effects. It produces a similar spectrum of pharmacological
effects to psychomotor stimulants in Schedule II of the 1971
Convention on Psychotropic Substances.
Dependence potential
There have been few animal studies regarding the dependence or
abuse potential of amineptine. However, some clinical studies
indicated that amineptine has both dependence and abuse potential,
particularly in patients with a previous history of substance abuse.
Clinical observations of significant abuse and dependence are
reported in patients treated with amineptine in France. Its
dependence potential appeared to be associated with its psychomotor
stimulant effect. Withdrawal has been clinically manifested by
anxiety, insomnia, psychomotor agitation or bulimia. Instances of
dependence have been reported in Europe and Asia.
Actual abuse and/or evidence of likelihood of abuse
Amineptine abuse has mainly been reported in Europe and Asia. It
has been withdrawn from the market in France, where the drug was
developed a few decades ago, for reasons of considerable
hepatotoxicity and abuse. Despite this measure, medical use in
developing countries, as well as abuse still continues. The abuse-
related adverse drug reaction reports for amineptine collected by
the international drug monitoring programme indicate a larger number
of case reports of abuse and dependence than anorectic stimulants
currently placed in Schedule IV of the 1971 Convention on
Psychotropic Substances, such as amfepramone. Response of
governments to the WHO questionnaire also indicated limited
diversion and abuse of the drug. Some reported hospital admissions
due to adverse consequences of amineptine abuse.
Therapeutic usefulness
The therapeutic usefulness of amineptine is low because of
hepatotoxicity, secondary features such as acne eruption and anxiety
and the availability of safer antidepressants. Of the 103 countries
that responded to the WHO questionnaire, only 17 indicated
amineptine use.
III. Discussion
Although WHO has made specific scheduling recommendations for
amineptine, the CND is not obliged to follow the WHO recommendations.
Options available to the CND for substances considered for control
under the Psychotropic Convention include: (1) Acceptance of the WHO
recommendations; (2) acceptance of the recommendations to control, but
control the drug substance in a schedule other than that recommended;
or (3) rejection of the recommendations entirely. Amineptine is not
approved for marketing in the United States and is not a controlled
substance in the United States. Therefore, current controls in the
United States on amineptine do not appear to meet the requirements of
the recommended Schedule II of the Psychotropic Convention.
IV. Comments
Interested persons may, submit to the Dockets Management Branch
(see ADDRESSES) written comments regarding this notice. Comments are to
be identified with the docket number found in brackets in the heading
of this document. Received comments may be seen in the Dockets
Management Branch (see ADDRESSES) between 9 a.m. and 4 p.m., Monday
through Friday.
Dated: January 28, 2003.
Margaret M. Dotzel,
Assistant Commissioner for Policy.
[FR Doc. 03-2456 Filed 1-31-03; 8:45 am]
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