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MCNEIL CONSUMER
PRODUCTS
COMPANY,
CAMP
HILL ROAD. FO
TJ. S. Department of Health and Human Services
Dockets Management Branch (HFA 305), Room 4-62
Food and Drug Administration
5600 Fishers Lane
Rockville,
MD 20857
c-2
5';:
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5
g
2
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z
Re: Docket Number 76~05@
(Cold,
Cough, Allergy,
Bronchodilator,
and
Antiasthmatic
Drug Products for Over-the-Counter
Human Use; Tentative
Final Monograph for OTC Nasal Decongestant Drug Products)
z
Gentlemen:
In the Federal
Proposed
Register
Rulemaking
of
under
January
21 CFR Part
identifying
conditions
Decongestant
products
are generally
misbranded.
The Proposed Regulation
Monograph
directions
under
comments presented
1.
Labeling
McNeil
21 CFR 341.80
"Exclusivity
lists
341,
under
the FDA published
establishing
(b)
a Tentative
Over-the-Counter
which
recognized
a Notice
as safe
included
labeling
and (d),
which
are
the
Final
Nasal
H
and not
and effective
indications
of
and dosage
subject
of
the
not
prescribe
Policy"
of
Company believes
terms
Rather
than prohibiting
should
permit
from which
or misleading.
that
labeling
the use of alternative
manufacturers
communicate the desired
false
1985,
below.
Consumer Products
exclusive
15,
label
to
choose
indications,
FDA should
indications
truthful
consumer
must be drawn.
terminology,
oriented
FDA
language
so long as such language
to
is not
"'
It
is
noted
Policy"
that
on April
FDA proposed
22,
certain
1985 and McNeil
revisions
will
submit
to
the
"Exclusivity
comments on that
proposal
separately.
2.
Indications
for
Use [341.80(b)]
The Tentative
Final
containing
products
indications
believes
be
active
phrase
"For
or
are
products
extraneous,
but
oral
potentially
particularly
true
for
combination
cold
inappropriate
for
persons
suffering
allergy
McNeil
therefore
amended
to
allow
requests
manufacturers
indications
noted
above,
which
product
is
the
allergy
341.80(b)(l)
or
that
sinusitus].
be modified
the
to
directed
Accordingly,
to read:
(P
rhinitis)
or
McNeil
of
the
above
of
the
all
decongestants
to
three
may not
consumers.
which
common
This
is
may
be
totally
of
the
TFM be
or sinusitis.
choose
[i.e.:
nasal
The use of
products
indications
as appropriate
three
treatment
nasal
confusing
of
decongestants,
the
oral
relief
all
label
sinusitis."
different.
containing
for
carry
(allergic
all
nasal
for
entirely
to
with
require
whom products
and sinusitis
all
to
calls
temporary
hay fever
containing
to
the
associated
inappropriate
products
Decongestants
ingredients
(cold),
allergies
audiences
for
OTC Nasal
common cold
is
all
allergy
indications
only
it
for
The consumer
the
respiratory
that
indications
cold,
to
due to the
upper
for
decongestant
limited
congestion
other
Monograph
for
from
among any
the consumer
either
it
section
the
is
of
market
the
segment
common cold
requested
that
three
to
(cold),
21
CFR
"The
labeling
of
indications
the
product
under
includes
the
contains
heading
a statement
the
(select
hay
temporary
one of
fever
relief
the
of
(allergic
indications:
nasal
following)
the
which
"Indications"
one or more of the following
"For
of
congestion
the
rhinitis)
due to
common cold
or
(cold),
associated
with
sinusitis."
Other Allowable
To permit
"other
Indications
meaningful
allowable
alternative
alternate
consumer
Indications"
statements
341.80(b)(l)
[341.80(b)(2)]
given
rather
than
oriented
in
in
the
label
indications,
TFM should
addition
to
the
be available
those
permitted
as
under
above.
0
McNeil
also
those
already
oriented
head
(b)(2)(i)
"(2)
that
the
included
terms,
stuffed-up
341.80
believes
in
allowable
since
the
be
in
Therefore,
clogged-up
are
synonymous
they
are
"temporarily
e.g.
McNeil
requests
341.80(b)(l)
As an alternative
above,
the
any of the following
relief
that
nose,
nose,
(select
stopped-up
nose,
stuffed-up
(3)
head,
to
the
labeling
of
statements:
of
one
nasal
stuffy
of
the
stuffi-
head.'
with
consumer
relieves
to read:
temporary
stuffy
permitted,
indications.
may contain
ness,
and
head).
the product
following):
341.80(b)(2)
(stuffy
listed
For
below
also
indications
(i)
terms
should
be modified
Other
underlined
21 CFR
‘.. r
\
1
3.
Warnings
[341.72(c)]
The current
text
FDA mandated warning
and also
contains
statement
for
required
in
adults
(c)(l)(i)(d)
the T F M calls
and children
other
warnings.
341.80(c)(l)(i)(c)
and in
redundant
For example,
language.
language
to
read
like
essentially
as
warning
precautionary
duplicates
McNeil
read
a m e d ical
inappropriate
a drug interaction
Therefore,
be m o d ified
to
some cases
for
which
tends
requests
given
below
statements
that
and
21
that
341.80
be eliminated:
(c)u
Do not
heart
take
this
disease,
disease,
product
depression,
diabetes,
enlargement
of
or
the
if
you are being
high
blood
have difficulty
prostate
pressure,
in
gland
treated
unless
for
thyroid
urination
directed
due to
by
a
doctor."
f
Similarly
for
that
CPR 341.8O(c)(l)(ii)(c)
21
products
341.80(c)(l)(ii)(d)
(c)
for
give
heart
blood pressure
Labeling
m a d e in
l341.72
for
children
be
under age 12,
m o d ified
as
it
is
requested
outlined
below
and
this
product
disease,
to
thyroid
or depression
unless
children
who are
being
disease,
diabetes,
high
directed
by a doctor."
[341.80(d)]
Recommendations for
McNeil
labeled
be eliminated:
"DO not
treated
4.
CFR
Changes in Pediatric
Consumer Products
the
(d)]
pediatric
Company's
dosing
recommends the
schedules
of the monograph:
(4)
Dosage Schedules
used in
the
following
"Directions"
changes
be
section
A.
Addition
of
a pediatric
B.
C.
an optional
dosage
dosage
equivalent
unit
additional
age
dosing
concept;
unit
Addition
of
optional
basis
package
labeling.
Addition
of
schedule
to
developed
groupings
which
l/8
to
utilizes
the
the
adult
better
concept
of
dose and includes
utilize
the
pediatric
and
a weight-based
as
schedule
part
of
the
a professional
that
could
recommendations
dosing
dosage
be incorporated
schedule
for
children
on an
in
consumer
under
2 years
of age.
Recommendation:
divided
New
targeted
primarily
schedule
Adoption
patient
of
using
either
schedule
through
for
based
more
on
pediatric
patient,
dosing
schedule
in
adults,
it
growing
to
fin@y
is
currently
is
which
reasonable
that
used
(1)
in
for
a
dosing
doses
to the
Proposed
in
various
of combination
provide
to
the
and reported
between
dosage
continue
in the Tentative
(5)
need
products
years.
formulation
also
a
market
For
of incremental
consistency
the
nonprescription
patients.
there
Drug Products
provide
the
administration
similar
consistency
for
in
pediatric
use,
his/her
system
3) would
targeted
or
pediatric
Analgesic
for
available
adult
provide
a dosing
(2,
allow
currently
for
would
OTC Internal
products
the
toward
that
literature
would
products
intended
pediatric
for
dosing
age breaks.
Most cough-cold
are
pediatric
Final
to
the
Monograph
published
monographs
and
products.
For
recommendations
allow
the
Monograph.
option
for
of
The Pediatric
Dosing
pediatric
dosing
developed
that
by
incremental
using
growth
unit
for
in
be administered
the
administered
Because it
adult
is
The standard
drug
one-fifth,
adult
dosing
into
have
one-eighth
unit
of
already
mental
Analgesic
can
unit
of
been
the
in
age-breaks
can be
pediatric
patient
with
typical
PDU concept
fixed
be used
the
allows
dosing
products
increments
adult
evaluated,
incremental
adult
use with
are
can
long
unit
but
to
dose
is
acetaminophen
consistent
with
is
such
Drug Products.
(6)
pediatric
of
use.
a recognized
ingredient.
be applied
independent
dosing
one-eighth
intervals
of
can
of
the
usual
as one-twelfth,
one-tenth,
meet
for
a PDU that
ranges.
consistent
the
needs
be
one-eighth
of
with
seven
incremental
In addition,
with
Proposed
the
adult
or
pediatric
is
and aspirin
the
orally
or specific
as
can be developed
weight
for
all
rates.
do not
Using
framework
usual
as
doses,
essentially
and fractions
category
concept
dosing
for
intended
drug elimination
pediatric
seven
consistent
ranges
intervals,
account
a dosing
and/or
schedules
growing
relatively
to any drug
as satisfactorily.
dose,
periods
system
dosing
fractions
formulations
with
can be applied
pediatric
Other
the
the
weight
The most appropriate
dose.
addition,
based on standard
to take
dosing
standardized
and effectively.
PDU dosing
or
pediatric
ranges
weight
In
a relatively
need of
preparations
half-life
adjusted
the
over-the-counter
it
dose,
and
administration
safely
basis,
with
age
Using
concept.
(PDU) as the
children.
oral
Importantly,
(PDU)
are consistent
pattern
intended
Unit
the usual
age
a PDU that
pediatric
products
Monograph
and the
for
is
dosing
increInternal
..
*iv:
’
I
1
Application
of
For products
whose labeling
five
the
age breaks
professional
desired.
pediatric
would
labeling
dosing
is
unit
lim ited
be incorporated
also
could
concept
to
to children
into
be developed
consumer
2 years
package
for
labeling.
and older,
only
Additional
labeling.
the younger age child
if
(see below)
The following
summarizes
pediatric
dosing
units
constant,
incremental
the
that
dosing
recommended age periods
would
be required
throughout
at
and the
a given
the pediatric
number of
age to
m a intain
age period:
RECOMMENDED
PEDIATRIC DOSING SCHEDULE
Number of Pediatric
Dosing
Units (PDUs) for that Age Range
Age Ranges
6
9-10
5
6-8
4-5
2-3
4
3
2
Note:
Eight PDUs would be the
children
under
two
recommendations.
The following
groups
relative
in
equivalent
years,
compares the age groupings
the
Tentative
doses as fractions
F inal
of
for
Monograph
the adult
ranges.
(7)
0
of the usual adult
professional
see
the PDU schedule
showing
dose for
the
age
For
dose.
labeling
with
the age
breaks
each of the specific
and
age
COMPARATIVE AGE GROUPINGS FOR PROPOSED PDU DOSING SCHEDULE AND
TENTATIVE FINAL MONOGRAPHSCHEDULE WITH DOSES DISPLAYED AS FRACTIONS
OF THE USUAL ADULT DOSE.
Fractional
Dose Administered
TFM
PDU
Age
Schedule
Schedule
(years)
1.0
1.0
Adult
--------------------___________^________------------------0.75
11
0.625
10
II
9
8
7
6
0.50
5
4
3
2
0.375
this
to
dextromethorphan,
Using
the
dosing
11
the
schedule
dose.
For
mg/ kg.
four
across
approach
the
drug
utility
of
compounds:
pediatric
calculated,
various
this
drug
approach,
(monograph)
we have applied
acetaminophen,
that
would
range
of
unit
For pseudoe-
with
a dosing
range
tains
complete
dosing
dosing
dosing
0.6
would
chlorpheniramine,
to
0.10
for
(8)
be
established.
range
dosing
mg/kg.
of
For
a dosing
pediatric
dosing
these
to
four
1.5
would
aceta-
produce
range
unit
using
of
would
a
15 mg/kg
per
be 0.5
mg,
dextromethorphan,
mg/kg.
agents
mg/kg
For
10 to
unit
mg, with
1.0
identified,
be 80 mg and would
a dosing
pediatric
the
can
schedules
the
approximately
schedules
units
would
in
be 2.5
phedrine,
of
unit
result
chlorpheniramine,
dosing
dosing
and
pediatric
a dosing
pediatric
this
PDU system,
dosing
with
labeling.
and pseudoephedrine.
ranges
minophen,
11
II
II
0.25
To demonstrate
concept
0.25*
11
of
categories.
11
II
II
II
11
11
II
*Professional
Applicability
0.50
0.3
the
to
0.5
be 7.5
mg,
Appendix
A con-
the PDU system.
.
To further
illustrate
PDU dosing
schedule
comparison
illustrates
this,
with
unity
the mg/kg dose/weight
demonstrates,
greater
weights
for
the
for
children
lowest
single
single
dose exceeding
for
by using
breaks,
that
of
the
therapeutic
Applicability
of
yet provide
greater
the
in
with
which
The single
decongestants
to
all
no
doses
we
the Tentative
Category
can be applied
included
As can be seen, a reasonable
the
Final
of dosing
in
a+
approach
approach
a
with
range.
this
at
figure
doses,
consistency
Appendix C summarizes the dosing
to
as Category
dosing
schedule
all
I
nasal
oral
Category
I
recommendations
I ingredients
Nasal
for
all
in the TFM.
can be established
for
each
nasal decongestant.
summary, we have
pediatric
dosing
consistent
with
Analgesic
As
a result
doses in
Decongestants.
Category I oral
sets
age ranges
doses.
This
In
age.
narrower
decongestants.
nasal
arbitrarily
of
produces
index
This
based on
ages,
doses are between 70 and 75% of the index
Monograph on a mg/kg basis,
oral
schedule.
ages 6 and 12, based on
12 years
recommend do not exceed the maximum single
an effective
specific
The comparison
6 and
incremental
for
calculated
PDU schedule,
number of
ratios
age.
ratio
1) compares the proposed
approved TFM dosing
dose/weight
percentile
TFM doses
B (Figure
the already
50th
the
Appendix
provided
schedule
those
data
that
provided
in
Drug Products.
(9
supporting
the
utility
of
incorporates
additional
the
Monograph for
Proposed
age
a
new
breaks
Internal
,
We also
,
four
have reviewed
different
monographs
decongestants,
approach
the
This
dosing
unit
dosing
of 2-3,
Recommendation:
There
is
weight
children
are
approach
the usual
of
in
weight,
can
be
this
4-5,
6-8,
9-10,
a
schedule
on package
is
very
age breaks
pediatric
small
to
have
and
in
from
I oral
nasal
consistent
the
pediatric
a standard
pediatric
adult
with
dose
available
labels.
age
for
an optional
Such schedules
and is
a given
patient
especially
their
are
some
when
age and when children
dosing
and while
can be
useful
schedule.
While
has been recommended on the
area,
there
standard
known,
for
and body surface
of
drugs
Schedule
consumers
or
rational
concept
the
four
of Category
medications
benefit
interrelated,
list
to
and 11 years.
Based Dosing
large
dosing
is
the
one-eighth
when weight
very
the
that
this
nonprescription
is
dosing
children
age,
entire
that
Weight
related
drugs
and to the
incorporates
an additional
used with
of
of
approach
(PDU)
increments
application
demonstrating
to
patient.
the
each
specific
of
these
dosing
basis
of
parameters
preferences
for
each
approach.
While
body
surface
change
that
occurs
growth
parameter
area
in
that
may reflect
the
is
in
is clearly
not a parameter
of
as
weight
a
merit.
Weight
surface
area
dosing
growing
that
and thus,
by body surface
for
are
dosing
is
reasonably
by weight
(10)
body
the
of
pediatricians'
drugs
similar
is
the
surface
used by parents.
dosing
area.
accurately
child,
common use in
parameter
changes
more
magnitude
area
is
not
offices
As a result,
has
to
far
the
a reasonable
more
changes
of
a
and
the use
practical
in
substitute
body
for
,
While
the
age has the
simplest
reasonable
advantage
parameter
guide
consideration
for
dosing
schedule
health
professionals
wide
offers
a
almost
the
in
in
who would
Recommended Weight
Schedule.
like
universally
and while
child
that
for
into
a weight-based
those
consumers
Since
dose by weight.
recommend that
takes
one
occur,
benefit
to
known and is
age can be used as a
provided
growth
significant
we would
always
is
use,
variations
known,
not
it
consumer
growth
to
the
that
or
weight
is
the
weight-based
schedule
be
to avoid
unnecessary
consumer
and
optional.
health
professional
available,
review
with
that
the pediatric
weight
the
age
breaks
that
simplicity
of
unit
deviate
order
when
weight-based
standardized
increments
dosing
schedules
but
ideal.
confusion
we recommend that
indicates
In
of
weight
12 pounds
concept.
in
We recommend that
ranges
are
by a few pounds from
the
pediatric
the following
are
made
be adopted.
Our
the
most
There are currently
12 pound increments
incorporated
schedules
and its
dosing
weight
that
consispnt
in use other
proposed
consistency
unit
schedule
herein,
with
concept
the
make it
be utilized:
RECOMMENDED
WEIGHT-BASED DOSING SCHEDULE
Weight Ranges
(pounds)
(kilograms)
33.0-43.9
72-95
27.0-32.9
60-71
22.0-26.9
48-59
16.0-21.9
36-47
11.0-15.9
24-35
Because weight
the
United
kilograms
Number of Pediatric
Dosing
Units (PDUs) for that Weight
6
5
4
3
2
is
still
States
in
included
the consistency
measured
pounds,
and remembered by the
the
proposed
as an alternate.
of dosing
that
occurs
(11)
schedule
Appendix
is
B (Figure
when these weight
Range
average
in
2)
ranges
parent
pounds,
in
with
demonstrates
are used.
.
Recommendation: Professional
In
order
guidance
to
provide
about dosing
professional
additional
of nasal
dosage schedule
based on the PDU system.
This
decongestants,
be adopted
for
Under Age 2:
professionals
1 yr
1.5
4-11 mo
1.0
we would recommend that
children
readily
to any appropriate
nasal
the Professional
Labeling
pseudoephedrine,
decongestant.
section
to 6 hours,
Adoption
children
would be
4 months to under 1 year,
not to exceed
7.5 mg every 4
not to exceed 30 mg in 24 hours.
of such a professional
to the health
For
H
one year of age, 11.25 mg every 4 to 6 hours,
45 mg in 24 hours;
a
under age 2 years
amended to read as follows:
Children
seeking
The schedule would be as follows:
No. PDUs
for
Children
to
assistance
42%
can be adapted
example,
Dosage Schedule for
dosage schedule would be of great
professional.
(12)
benefit
Summary of Recommendations
In
McNeil
summary,
on Directions:
Consumer
recommendations
with
dosing
decongestants:
1.
of nasal
We recommend that
optional
standard
incremental
2.
age-related
3.
schedule
dosing
age breaks,
that
in
consumer
schedule,
unit,
2-3,
the
package
9-10,
schedule,
consistent
with
of professional
to
the
dosage for
the
labeling
the
three
pediatric
directions
an
concept
and 11 years;
package
FDA add
for
an increased
consumer
as summarized
making
labeling
on
provides
6-8,
is
directions
based
that
4-5,
Company
FDA add to
schedule,
We recommend
changes
dosing
pediatric
weight
to
FDA add to
pediatric
We recommend that
optional
regard
Products
of
a
number
of
and
directions
newly
an
proposed
herein.
oral
children
/
nasal
decongestant
TFM a
below age two.
Sincerely,
MCNEIL CONSUMERPRODUCTSCOMPANY
Regulatory
set
57638
(13)
Affairs
. -’
REFERENCES
1.
Proposed
Monograph
Antirheumatic
2.
Done,
Products,
A.K.,
Yaffe,
and children"
3.
Temple,
2.
A.R.:
3:321-327,
For
Federal
S.J.,
Pediatrics
"Pediatric
OTC
Internal
Register
and Clayton,
95:617-625,
dosing
of
1983.
(14)
Analgesic,
42:35346-494,
J.M.:
"Aspirin
Antipyretic
and
1977.
dosage
for
infants
1979.
acetaminophen"
Pediatric
Pharmacology
APPENDIX
PEDIATRIC
A.
DOSING
DOSING
UNIT
SCHEDULE AS
APPLIED
TO
ACETAMINOPHEN, CHLORPHENIRAMINE, DRXTROMETHORPHAN,AND PSEUDOEPHEDRINE.
General
PDU Dosing
Schedule
No. PDUs
Age (years)
11
6
9-10
5
6-8
4
4-5
3
2-3
2
-------------------------------------------
1
1.5
4-11 mo.
Pediatric
Dosing
dextromethorphan
1
Unit
schedule
for
acetaminophen,
chlorpheniramine,
and pseudoephedrine.
"Usual" adult dose:
Pediatric
dosing unit:
Dosing Schedule
11 yrs
9-10 yrs
6-8 yrs
4-5 yrs
2-3 yrs
1 yr
4-11 mo.
Dosage:
Approximate
Approximate
dosing
mean:
range:
Acetaminophen
650-1000 mg
80 mg
Chlorpheniramine
4.0 mg
0.5 mg
480
400
320
240
mg
mg
mg
mg
160 mg
3.0
2.5
2.0
120 mg
80 mg
0.75
0.5
12.5 mg/kg
lo-15 mg/kg
mg
mg
mg
1.5 mg
1.0 mg
0.08
.065-,095
(15)
mg
mg
mg/kg
mg/kg
Dextromethorphan
20 mg
2.5
mg
15.0 mg
mg
10.0 mg
7.5 mg
5.0 mg
12.5
3.75
2.5
0.4
0.3-0.5
mg
mg
mg/kg
mg/kg
Pseudoephedrine
60 mg
7.5 mg
mg
mg
mg
mg
15.0 mg
45.0
37.5
30.0
22.5
11.25
7.5
mg
mg
1.25 mg/kg
1.0-1.5
me/kg