## Final Minutes- April 22, 2002 

##  Nonprescription Drugs Advisory Committee with consultants from

## Pulmonary - Allergy and Dermatological Drugs Advisory Committee

# 

Food and Drug Administration

Center for Drug Evaluation and Research

Holiday Inn, Bethesda

**Claritin for OTC Use (loratadine, Schering Plough)**

**NDA 19-658, NDA 20-704, NDA 20-641**

Prior to the meeting, the committee had reviewed background material
from Schering Plough and from the FDA. The meeting was called to order
by Louis Cantilena, M.D., Ph.D. and Sandra Titus, Ph.D. read the
conflict of interest statement into the record. There were approximately
120 people in attendance.

**Attendance:**

**NDAC Members Present:** Louis Cantilena, M.D.., Ph.D., NDAC Chair and
Chair of the meeting, Edwin Gilliam, Ph.D., Julie Johnson, Pharm.D.,
Hari Sachs, M.D., Edward Krenzelok, Francis Lam, Pharm.D., Donald Uden,
Pharm.D., Henry Williams, M.D., Leslie Clapp, M.D., Frank Davidoff,
M.D., Alastair Wood, M.D.

**NDAC Members Absent:** Richard Neill, M.D.

**NDAC Voting Consultants:** Ralph D'Agostino, Ph.D.

**Pulmonary-Allergy Voting Consultants: M**ark Dykewicz,M.D., Jesse
Joad, M.D.,

Stan Szefler, M.D.

**Dermatological Voting Consultants**: Lloyd King, M.D., William
Rosenberg M.D.,

**Industry Guest: (non voting)** Michael Alfano, M.D.

**FDA Participants:**, Robert Temple, M.D., Sandra Kweder, M.D., Jonca
Bull, M.D., , Charles Ganley, M.D., Jonathan Wilkin, M.D., Linda Katz,
M.D., Badrul Chowdhury, M.D., Ph.D., Mathew Holman, Ph.D.

**FDA: Overview Of Today's Issues**

Charles Ganley, M.D., Director OTCDP, outlined the purpose of the
meeting.

**Schering Presentations:**

John Clayton, Ph.D, Senior VP Scientific and Regulatory Affairs
presented an overview. Eugene W. Monroe, M.D. Department of Dermatology
from the Medical College of Wisconsin and consultant to Schering
presented a clinical overview of urticaria. Stephen Neuman, presented
the CIU studies and Dr. Clayton concluded with a risk benefit analysis.
Questions followed the presentations.

**FDA Presentations**:

##### 

Jonathan Wilkin, Director, Dermatologic Drugs presented an Overview on
Urticaria. Badrul Chowdhury, M.D., Ph.D described the clinical study
design issues for the Approved H1 Antihistamines with CIU Indication.
Matthew Holman, Ph.D., presented OTC Issues: US Regulatory History,
Foreign Marketing and Label Comprehension Study. Charles Ganley, M.D.
concluded the presentations by raising Issues for the Committee's
deliberation on the use of Claritin for Urticaria in the OTC setting.

**Open Public Hearing**

Gary Kay, Ph.D., Janet Engle, PharmD., and Joseph Ferguson, M.D.
presented.

**Questions for Committee Deliberation:**

1.  Is urticaria a disease process appropriate for an OTC indication?

**The committee altered this question to:**

**Could urticaria be a disease process appropriate for an OTC
indication?**

**Yes = 16 No=0 (one member absent for vote)**

a.  If yes, should the indication be for chronic idiopathic urticaria
    (CIU)/hives or should it be broader such that it includes acute
    urticaria / hives?

**Yes for broader indication = 14**

**Possibly broader =1 (because of concern for anaphalaxis)**

**Broader if stated treat hives after seeing an MD =1 (because we would
avoid a misdiagnosis and closer to what the sponsor is seeking)**

**There was consensus that everyone with hives would be likely to use a
product that was approved for any form of hives.**

2\. If your answer to Question 1 is "yes," are there sufficient data to
support an OTC switch of loratadine for CIU or a more general urticaria
claim?

**The committee felt that it was too difficult to consider a broad
indication, which is desirable as the context for this question. Hence
the question became:**

**Are there sufficient data to support an OTC switch of loratadine for
CIU?**

**Yes for CIU indication =16 No=0**

> **(One person not present for vote)**

**Are there sufficient data to support an OTC switch of loratadine for
general hives?**

**Yes for general hives = 0 no for general hives = 11**

**Don't know/insufficient data =5**

If not, what other types of data are needed (such as clinical trial(s)
for efficacy, safety, label comprehension, or actual use)?

**[The following viewpoints were expressed:]{.underline}**

**Would be nice to see a Meta -analysis of all the research on hives.**

**Would be nice to know if people could understand what CIU is versus
hives so that it would be labeled appropriately.**

**Probably don't need clinical trials because the data are probably
already out there.**

**Are there studies that use it for acute hives? (Sponsor thought there
were not any studies)**

**A label comprehension study to see if effectively labeled**

**Seems negative to stick with CIU indication when know that the broader
indication will occur.**

**Use of loratadine sounds safe and cannot learn a lot from spontaneous
reports.**

**Even without data, indication should go just "hives" because it is
more understandable.**

**Additional Studies that included subpopulations (underrepresented)
would be needed to go forward with a more general indication.**

3\. If your answer to Question 2 is "yes," what are your recommendations
for appropriate labeling of loratadine, with regard to indications,
warnings, and directions?

**[The following comments were individually suggested and there was no
attempt to get consensus:]{.underline}**

**Label should maximize warning for anaphylaxis**

**Label should indicate that vascular process is possible**

**Clear definition of chronic or recurrent and if possible provide a
picture.**

**Use of the term "unexplained hives that may keep coming back", may be
appropriate for CIU explanation.**

**Blister packs may be a problem because information that a consumer
needs from the packaging could get lost.**

**Call it hives rather than CIU**

**Use a list, such as 10 reasons to consult a doctor.**

**How long should one continue treatment?**

**Call 911 if respiratory problems.**

**Be careful not to overstuff the label and need to prioritize
information.**

**Stress that it is a once a day pill.**

**If chronic label then a statement that you saw a doctor and he did not
know the cause of the hives (explain idiopathic).**

**If broader claim, would take out precaution.**

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 April 22, 2002 meeting of the
Nonprescription Drugs Advisory Committee and that these minutes
accurately reflect what transpired.

Sandra Titus, Ph.D. Date Louis Cantilena, M.D., Ph.D. Date

Executive Secretary, NDAC Chair, NDAC