AMERICAN
ACADEMY COMMITTEE ON
OF
PEDIATRICS
DRUGS
“THERAPEUTIC
ORPHANS”
drugs which and
and
AND
requiring
THE
PACKAGE
of useful these unsupported more
INSERT
package claims to the breaking for
exercise
I
This
N
the are
practice
of pediatrics,
revision them the he carry
The
inserts thus to
Drug effective
drugs
not approved Administration in children in in used
been
for
by the Food ( FDA) as safe are to
1962
to eliminate make Is when which
is not.
and
practitioner. his the law patients No,
his
prescribed the fact
carry
daily. that many such clinical
establish “orphan-
is due
released
part
since
pediatrician prescribes the
physician
drugs
may
an
“orphaning in the deviates insert must in
are used
cause?” use from and if
clinicians
he
pro-
ing “not
studies
clause” to be
have
the in
package children,
insufficient
its use.”
insert since
to
as,
fessional However, lions actions fend his malpractice
Many
judgment if he occur, he in the package position suit.
drugs
of any the adverse there
drug. instrucreto deis in the in the a use if it a
recommendations
What
is the dias a
status
rective
of the
to
package
insert?
Is it a legal
be court
by
prepared
a guide
the physician, for the physician
or is it intended in prescribing
drug? The package insert, by legal definition of the Federal Food, Drug and Cosmetic Law, is the official information piece for a drug. The information it contains is derived from data ted The drug
approved
treatment
of
conditions The firm product FDA
to
not
listed
package insert. pharmaceutical for has for ations may the
yet
cannot include
require a new even
the
drug
in
the insert
supplied by the insert
manufacturer,
by is
investigators firm and but
The
and to the printed
Food,
submitFDA. by must
Drug
pharmaceutical written
the FDA.
been clinically tested and found useful a given problem. Economic considerare influence company.
included
cannot
the be
and
among such
in the
a number a policy use
of factors on for his
insert,
that part of is not
man-
its contents in
known
the a drug
the
by full
If a new
advertise
Cosmetic
quires
Law,
disclosure
as use
amended
of all
1962,
facts
reper-
package
ufacturer
product insert
for is Ic-
taming great insert, the
to the
of the
drug.
Therefore,
a
that
particular
use.
The
package
deal of information is included in the including the chemical structure of drug, a summary of its pharmacological clinical indicaprecautions, dosage recomdosage package before forms. inserts the apDrug not the
these
gaily binding on the manufacturer ing the conditions under which mote that proved disease In
ity
in limithe can prorecognized is ap-
the
use
of the fact not
drug. generally failure treatment construed about it is important the to use for a drug
and toxicological action, its tions and contraindications, reported adverse reactions, mendations, I’sIany proved Amendments
were required
Another
a physician’s as effective might to be the not be the be this,
a specific that availabilthe
and drugs by the of
to
available have FDA
as malpractice.
regard
of
physician it or would from cessfully
in a liability
informed
the
basis
effectiveness
of evaluations
1962 when manufacturers show the safety but of their products. On
of the efficacy of
drug and base his decision to use to use it on rational grounds. It unlikely package as evidence
suit.
that insert
information could be the physician
used
taken sue-
older the tional
*
drugs National
by panels of experts selected Academy of Sciences-NaCouncil,
the
are some
by
against the
physician is illuswhen used a conthat
enuretic
Research
In Canada, ) is the
there
the
and agency
FDA
Drug to the
is now
Directorate FDA.
in
The trated in tile
dilemma treatment study drug
was was
facing
Food
minor
by imipramine was useful dry.” defined,
Vol. 46,
( Tofranil)
of enuresis. published in Its but
No. “training
( FDD
though
In
1965
comparable
Alpolicy
differences
trolled this children
tion
showing mechanism it appeared
5, November
and
the
equally
mode of operation between concepts set forth in the
to both countries.
the two agencies, statement apply
to be not
of
ac-
to be
1970
PEDIATRICS,
811
812
effective
PACKAGE when of 5 and at bedtime. given to children in a dosage publication widely A straw Cleveland imipramine examines the imipramine, treatment conditions of for one with between up to of used poll area
INSERT the view that guide with reports.’ Committee Modell. on therapy knowledge sound shown effective in just that in adults, from because the the
the
the should
insert to the be
should physician; judged publications
be viewed its recoinon an and concurs insert equal
as
the
age
12 years Following
a useful mendations
footing
50 mg
this paper, imipramine became for the treatment of enuresis. of 15 pediatricians that 12 had condition. insert are
is
other on but should derived scientific
rewith
in When supplied clear: listed
the
search The Dr. useful sion live When have and disease
Drugs the from data
showed for this package tvo
enuresis
prescribed
The
package
contains dccisources. which safe on cumula-
information,
physician’s many exist
be based
points
( 1 ) the
under
not
the use statement mended
of age.
of this drug; and ( 2 ) there is a clear that the drug is not recomfor use in patients reaction how would under occurred a court 12 years and react litif If a severe followed,
a drug the it should a sick its But, physician of the to add
is reasonably not with has should drug should
FDA, or
treatment child use if used
of a specific necessarily the not under be be same been these caurein the
be withheld disease studied tious
ported
igation
a physician admitted to the for the treatment of enuresis prohibitions the published cian’s judgment suffice? themselves testimony community in the clinical in package
use of this drug in view of the insert? the the Would physidrug, made medical in purpose. the
in children. and
to
circumstances
use
study, plus prescribing
manufacturer,
medical
concerning
tion must
literature
to the
knowledge situaof the that or it age
Possibly, if other physicians available to give expert and used if the other drug physicians for this
such use. The be distinguished the is on unsafe Committee the or package basis contraindicated
foregoing from use insert in states infants
drug the
to
when drug
The purpose package insert tice of medicine.
cian
of the FDA control of the is not to legislate the pracAs in the past, the physi-
children be groups. The
of studies in that the
showing these pediatriclause” patient
ineffective feels
is the individual prescribing the drug. The fact that he followed the recommendations in the package insert does not absolve
cian is likely in the insert requires
treatment.
to ignore if, in his
the “orphan judgment, his medication or not this
him
from
responsibility nor
him
for does failure
harm
resulting the necinnot in insert package are
to his patient, recommendations
essarily render
to follow
a particular Whether legal
by the
for optimal places him not
opinion
in the
legally
package
culpable.
in yet
unusual
resolved
jeopardy
courts.
is a question
It is the
The
sent and
statements
approved
made
by
in the the FDA
of the not be formed
Committee a problem on the
that if the
this
practice and
should is well toxicolfollows in-
physician
themselves legally binding in his practice of medicine. no physician should rely
on the physician Furthermore, package in-
pharmacology
on the
ogy of the his patient’s
drugs he uses and closely response to treatment.
sert as his sole source of drug information. Drug dosages, as given in the insert, are gimides for instituting therapy. The dose
may
Changing the directives in the package insert, except to disclose pertinent new data, will not solve the problem of “therapeutic
key’s3
have
to be on the
increased patient’s
or decreased, response. the question patient must editor of has
deAnd, of be
orphans.”
stand, the
Echoing
Committee
Dr.
Harry
believes
Shirthat
pending
each time a drug is used, benefit versus risk to the considered. Dr. Walter
Pharmacology
the ment
ultimate to
solution ensure
requires in pediatric that are all
the clinical drugs
developpharused tested in
of programs
macology Modell,
and
Clinical
taken
Therapeutics,
infants and children for safety and efficacy.
adequately
AMERICAN Suisii
CHARLES
ACADEMY
OF
PEDIATRICS C. Smmay,
813
J.
F.
YArn,
WEISS,
M.D., M.D.,
Chairman Interim
Huuiy
M.D.,
Consultant
Chairman
REFERENCES M. CANN, M.D. P. GoLD, M.D. M. D.
KENNEY, JR., RILEY,
Howiw
ARNOLD FREDERIC
1. Poussant,
A. F.,
and
Ditman,
in
K. S. : Controlled
Hms IRwIN
LEO
M.D. M.D.
study of childhood
2. Modell,
imipramine
the
treatment
67:283, “FDA
of
enuresis.
J. Pediat.,
comment,
1965.
Censor-
W. : Editorial
SCHAFER,
M.D.
M.D.
ship.” 3. Shirkey,
orphans.”
Clin. Pharmacol. H. : Editorial
STERN,
J. Pediat.,
Ther., 8:359, 1967. comment, “Therapeutic 72: 119, 1968.