**Docket No. FDA-2008-N-04661**

**Over the Counter Cough and Cold Medications for Pediatric Use; Notice
of Public Hearing**

Public Hearing for Over-the-Counter Cough and Cold Medications,  October
2, 2008

As a dad and a doctor, I find this a very scary topic. I used to think
that as long as my patient's or I dosed the children's cold & cough
medications right, then everything would be OK. Even though the drug
companies constantly point out that overdoses are "usually" the result
of dosing error, there have been over-doses of ALL THE MAJOR CHILDRENS
COLD AND COUGH MEDICINES even when given the correct dose (Your 'Notice
of Public Hearing' even eludes to this fact).^1^

Here are a few interesting facts:

1\. Last October 2008, the drug companies promised the FDA and the
country that they would change all their labeling to say "do not use"
for children under the age of 2. This past week (mid September 2008) I
went to 4 separate major pharmacies in two different states and examined
the labeling of all of the pediatric cough and cold medicines' boxes
that were on the shelf. Of the over 30 different boxes I examined, I
would only found 3 that mentioned "Do not Use" for children under 2!

The interesting thing is that at different pharmacies, the same
medication had different labeling. This is unacceptable! Despite knowing
that children are dying, the drug companies have mislead the FDA, the
medical community, and the public about their voluntary reforms.

If you think I am exaggerating, tonight on your way home, go to a random
pharmacy and read the labeling for your self. If you find 2 boxes that
say "Do not use" for children under 2, then you (or I should say, the
young families in that neighborhood), will be lucky.

2\. The number of infant deaths attributed to cold and cough medicines
is dramatically underreported. New research published in the Journal of
the American Academy of Pediatrics demonstrated that there were at least
"10 unexpected infant deaths that were associated with cold-medication"
in 2006 alone in the state of Arizona. Extrapolated over the North
American population, that would be over 500 deaths a year associated
with cold-medication!^2^

3\. These Medications were allowed to be sold as over the counter
because in the past, with limited research and limited post market
surveillance, they were "Generally Recognized As Safe and Effective."
They were therefore allowed to skip the safety and efficacy studies that
modern medications are now required to conduct before they are allowed
on the market.

Qualified experts no longer generally recognize these medications as
neither safe nor effective for children. Therefore, the logical
conclusion is that they should immediately loose their protected status
and be removed from the market. If at some point, they can establish
themselves as being safe and effective, then and only then, would it be
prudent for them to return to the market.

**[Response to the FDA's Questions]{.underline}**

**1. What types of studies, if any, should be conducted to assess**

**effectiveness and or safety, and determine appropriate dosing of cough
and cold ingredients in the pediatric population? How should these
studies be designed and powered?**

There are others, more qualified than me to comment on the design of
safety studies.

For effectiveness:

A multi-stepped approach needs to be used to find out if these
medications are effective.

First, we need ascertain what the public perceives a clinically relevant
out come would be for a child's cough. Parents and doctors should be
surveyed to find out what types of symptoms they feel are relevant.
(i.e. reducing the number of coughs a night, the severity of cough,
etc...)

Second, based on the symptoms targeted above, we need to survey parents
and doctors about how much relief would make it worthwhile to give the
medication to children. (i.e. they may feel that 50% relief in half of
the children would be worth while, or they may feel that only 10% relief
in 10% of the children would make it worth while).

Third, because these medications only treat symptoms, we then would only
need to power the studies to get the treatment effect that would be
Clinically Relevant to the public.

**2. Should cough and cold products for the pediatric population
continue**

**to be available OTC, or should they be made available only by
prescription?**

Qualified experts no longer generally recognize these medications as
neither safe nor effective. Therefore, they should be removed from the
market until the individual drugs have demonstrated safety and efficacy.
At that point they could be re-evaluated on an individual drug basis, to
see if they would be appropriate for OTC use.

**3. If the pediatric indications and dosing for cough and cold products
were no longer available OTC, would the public use the adult
formulations of the OTC monograph products for children, and thus create
a greater risk of misuse or overdose?**

This very well could be an issue, the risk would be minimized if there
were strong warnings on adult dosing of these medications. As I
mentioned above, these statements need to be required by the FDA because
the drug companies have already demonstrated that they will promise one
thing, and then promptly ignore their promise. If parents are still
misusing the adult over the counter medications and putting children
into the hospital or accidentally killing children, then the prudent
action for the FDA would be to revoke the OTC status of the misused
adult medications.

**4. Do the answers to the previous questions depend on the age of the**

**pediatric patients? If so, how should age be considered in making
regulatory decisions for these products?**

Deaths due to these products are almost exclusively in the under 6 age
group. Therefore, it is imperative that these medications be immediately
withdrawn from the market. The older age group still lacks evidence of
efficacy and therefore still needs to go though a process of withdraw
from the market unless they are proven safe and effective. But if there
is good evidence that medications marketed to older children will still
be used in younger children, then the medications for older children
need to also loose their over the counter status.

**5. At the time the monograph was established, FDA routinely
extrapolated**

**safety and efficacy data from adults to children age and over. Current
PREA standards permit extrapolation of pediatric efficacy \-- but not
safety based upon sufficient adult data. Does it remain appropriate to
recommend in the cough and cold monograph that children and over should
receive the same dose of medication as adults, without requiring any
additional studies in children in this age group? What additional safety
and/or efficacy studies should be required in this age group?**

New studies need to be done on the age specific age groups for all age
ranges. Although it may be permissible to extrapolate data on efficacy
in older children when there is an absence of other data to contradict
it, in this particular case, there is now data in the form of randomized
double blinded controlled trials, that **do not** imply these
medications are effective for older children either.

On top of that, according to a recent Cochrane Review the evidence for
these medications in adults is not very strong either.^4^

**6. What is the most appropriate method for determining pediatric
doses**

**that could be used as an alternative to the quarter- and half-dose
assumptions used in the monograph? Should products be dosed by age, by
weight, or both?**

I do not know enough about the pharmacokinetics data to have a good
answer to this. The amazing thing is that the companies selling these
drugs have not bothered to do these studies yet. Again, since we have no
good way of knowing what doses should be given, these products need to
be removed from the market until we have better data supporting a
specific method of dosing.

Another potential problem is that in the FDA Committee meeting last
October, the drug companies argued that the reason why the studies do
not demonstrate efficacy is because the drugs are **under dosed** for
children at the upper half of the age range. Their solution to this
would be to increase the dose. This is a problem because an increased
dose would **increase the chances of overdose** for these children.

**7. There are monographs for topical and intranasal ingredients to
treat the common cold. Should these monographs be considered in a
similar fashion to the oral cough and cold products? Are the answers to
the previous questions different for any subcategories of cough and cold
medicines (e.g., topical or intranasal products)?**

Because 35 years later, we still do not have studies that demonstrate
these medications work, they all need to be pulled from the OTC market
until they are properly studied and demonstrate efficacy and safety.

**8. The CCABADP monograph allows for the combination of ingredients**

**to treat colds and/or coughs. Should combination products be permitted
for all pediatric age groups? Should data be provided to support each
unique combination?**

The combination products have proven themselves to cause confusion and
are responsible for the many deaths. They therefore need to be carefully
regulated and studies on parental understanding of dosing should be
performed. Because of the dangers associated with these medications, if
the medications are sold as a combination, there should be evidence that
each particular combination is more effective than any of the individual
medications used alone.

**9. Can measurement errors in dosing be reduced using more
standardized**

**measuring devices or alternative dosage forms and, if so, what is the
best way to effect this change?**

If these medications had good evidence of safety and efficacy, then it
would be important to assure that they were dosed properly. It is very
difficult to accurately measure these medications for a verity of
reasons, (i.e. their viscosity makes them hard to pour, many people get
teaspoon and table spoon mixed up, etc..). Because there has been proven
danger with misdosing, it is important that these medications be
dispensed in a manor that allows parents to easily give a single correct
dose to children.

Jeffery L. Chamberlain M.D.

\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\--

^1^[Gunn
VL](http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term="Gunn VL"%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstract),
[Taha
SH](http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term="Taha SH"%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstract),
[Liebelt
EL](http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term="Liebelt EL"%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstract),
[Serwint
JR](http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term="Serwint JR"%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstract).
Toxicity of over-the-counter cough and cold medications. Pediatrics Vol.
108 No. 3 Septermber 2001.

^2^Mary E. Rimsza and Susan Newberry\
**Unexpected Infant Deaths Associated With Use of Cough and Cold
Medications**\
Pediatrics 2008 122: e318-e322.

^3^Dr. Suydam, page 82 of the transcript for the Joint Meeting of the
Non-prescription Drugs Advisory Committee and Pediatric Advisory
Committee on "safety and Efficacy of Over-The-Counter Cough and Cold
Products Marketed for Pediatric Use.

^4^Smith SM, Schroeder K, Fahey T. Over-the-counter medications for
acute cough in children and adults in ambulatory settings. Cochrane
Database of Systematic Reviews: Reviews 2008 Issue 1 John Wiley & Sons,
Ltd Chichester, UK DOI: 10.1002/14651858.CD001831.pub3