#### Final Minutes

## October 19, 2000

# Nonprescription Drugs Advisory Committee 

Food and Drug Administration

Center for Drug Evaluation and Research

Holiday Inn, 2 Montgomery Avenue, Gaithersburg, MD

**Safety Issues of** **Phenylpropanolamine (PPA)**

**in Over-the-Counter Drug (OTC) Products**

# 

> The meeting was held at the Holiday Inn, Gaithersburg, MD. Prior to
> the meeting, the members, consultants and guests reviewed background
> material from the FDA, from the Hemorrhagic Stroke Project conducted
> by Yale investigators and also material which the Consumer Healthcare
> Products Association had submitted for the committee's review. In
> order for the public to be informed, the background material was also
> available on the Dockets page the day before the meeting. There were
> approximately 150 persons in attendance. The meeting started at 8 a.m.
> and ended at 4:00 p.m.

**Attendance:**

**NDAC Members Present:** Eric Brass, M.D., Ph.D., Chair, Richard Neill,
M.D., Edwin Gilliam, Ph.D., Julie Johnson, Pharm.D., Hari Sachs, M.D.,
Louis Cantilena, M.D., Ph.D., Francis Lam, Pharm.D., Donald Uden,
Pharm.D., Henry Williams, M.D., George Blewitt, M.D.(non-voting)

**NDAC Members Absent:** Edward Krenzelok,

**Consultants: Statisticians and Epidemiologists:** Ralph D'Agostino,
Ph.D., Janet Daling, Ph.D.; Janet Elashoff, M.D.**, Neurologists:** Sid
Gilman, M.D., **Consumer Rep:** Susan Cohen

**Non-voting Guest:** **Epidemiologist:** Steven Kittner, M.D., MPH**;
Neurologist:** Steven Warach, M.D., Ph.D.

**FDA Participants:** Janet Woodcock, M.D., Robert DeLap, M.D., Ph.D.,
Charles Ganley, M.D., Linda Katz, M.D., MPH, Robert Sherman, Lois La
Grenade, M.D., MPH.

**Open Public Hearing: Three presentations**

Brian Strom, M.D., MPH, University of Pennsylvania representing
Whitehall Corporation; David E. Schteingart, M.D., University of
Michigan representing Chattem;

Sidney Wolfe, M.D., Director, Public Citizen's Health Research Group

**Historical Overview**

Robert L. Sherman, DOTCDP, described the Regulatory History of OTC PPA.

**Yale Presentation**

Walter Kernan, M.D. presented the Final Report of the Hemorrhagic Stroke
Project (HSP). The committee asked clarification questions following the
presentation.

**Consumer Healthcare Products Association**

The Consumer Healthcare Products Association had several speakers who
made comments about the HSP. R. William Soller, Ph.D., Senior Vice
President and Director of Science and Technology CHPA; Noel S. Weiss,
M.D., Dr. P.H., University of Washington; Lewis Kuller, M.D., Dr. Ph.H.;
Robert B. Wallace, M.D., Philip B. Gorelich, M.D., Charles H. Hennekens,
M.D., Dr. P.H., University of Miami School of Medicine. NDAC asked
clarification questions following all of these statements.

**FDA**

Lois La Grenade, M.D., M.P.H., OPDRA, presented her Divisions
epidemiological analysis of the agencies post marketing data on risks
related to PPA, and presented a critique of the HSP. Charles Ganley,
M.D., Director, DOTCDP gave an overview on how the FDA views safety
issues and how the deliberations today would contribute to bringing
closure to the PPA rulemaking.

**Committee Discussion and Vote:**

Following these presentations the committee discussed issues before
beginning the vote on the following questions. The Chair revised
question A and the subparts:

**Questions Related to the Results and Interpretation of the Hemorrhagic
Stroke Project :**

A.  Do the results from the HSP study for subjects in the 18 -- 49 years
    of age

suggest that PPA is **safe** from risk of hemorrhagic stroke,

suggest that there is an **association** between PPA and hemorrhagic
stroke,

or are **inconclusive.**

1.  For females 18 -- 49 using PPA as appetite suppression

    0=Safe 13=Association 1=Inconclusive

2.  For females 18 --49 using PPA as decongestants

    0=Safe 6=Association 8=Inconclusive

3.  For females 18 --49 using PPA on first exposure

    0=Safe 13=Association 1=Inconclusive

4.  For Men 18-49 using PPA as appetite suppression

    0=Safe 0=Association 14=Inconclusive

5.  For Men 18-49 using PPA as decongestant

    0=Safe 0=Association 14=Inconclusive

6.  For Men 18-49 using PPA on first exposure

    0=Safe 0=Association 14=Inconclusive

7.  For the entire population (men and women) using PPA as appetite
    suppression

    0=Safe 13=Association 1=Inconclusive

8.  For the entire population (men and women) using PPA as decongestant

    0=Safe 5=Association 9=Inconclusive

9.  For the entirel population (men and women) using PPA on first
    exposure

> 0=Safe 13=Association 1=Inconclusive

B.  Does the HSP provide information on which populations may be at
    greater or lesser risk?

    The issue was discussed, and members pointed out the limitation of
    subgroup data.

    **[Questions Related to the Availability of PPA in the OTC
    Market.]{.underline}**

C.  There is a body of data collected over the years that has suggested
    a possible association between PPA use and hemorrhagic stroke.
    Taking all currently available information into account, do the data
    support the conclusion that:

```{=html}
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1.  There is not an association between PPA use and hemorrhagic stroke?

2.  There is an association between PPA use and hemorrhagic stroke?

3.  The association still remains uncertain because of insufficient
    information?

> 0=no association 13= Yes Association 1=uncertain

D.  Considering your answer to question C, can PPA be considered to be
    generally recognized as safe for use as:

```{=html}
<!-- -->
```
1.  a decongestant ?

    0=Yes 12 = No 2=Abstain

2.  an appetite suppressant?

> 0=Yes 13=No 1=Abstain

a)  When answering this question, please address whether dose is an
    important consideration.

> During the discussion, members could not conclude there was any dose
> relationship however they did think there was some evidence to suggest
> this relationship.
>
> In making the risk/benefit analysis the following comments were made:
>
> What does the consumer loose if is taken off the market?
>
> One member stated that when a drug is only marginally useful, any
> degree of risk is much less tolerable.
>
> In discussing appetite suppression: In the long term 95% of people
> gain the weight back. Since there is no study on long-term use and the
> short term benefits for weight reduction are marginal no risks are
> acceptable. Regarding PPA for coughs many members felt here are other
> products that are equally good and that do not have this risk profile.

### It was pointed out that the PPA study was in reality similar to an actual use study because it described how consumers use products. It was troubling that a high proportion of subjects were hypertensive and were taking PPA. This indicates that labeling alone could not be relied upon to communicate warnings.

### Another member pointed out that the dose that seems to be causing the problem is not a massive overdose and so it becomes doubtful if one could effectively label or expect that consumers would follow the label.

A verbatim transcript of this meeting will be available on the FDA's
Dockets Management Branch Website approximately 30 days after the
meeting. The address is HTTP://www.fda.gov/ohrms/dockets/ac/acmenu.htm.

I certify that I attended the October 19, 2000 meeting of the
Nonprescription Drugs Advisory Committee and that these minutes
accurately reflect what transpired.

**[/s/]{.underline} [/s/]{.underline}**

Sandra Titus, Ph.D. Date Eric Brass, M.D., Ph.D. Date

Executive Secretary, NDAC Chair, NDAC