Non-Sedating Antihistamines

Rx-to-OTC Switch
NDAC & PADAC Joint Meeting
May 11, 2001
Franois Nader, MD
Senior Vice-President
Medical & Regulatory Affairs, North America
Aventis Pharmaceuticals, Inc.
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Overview
A switch of Allegra (fexofenadine) from a prescription
status to OTC would be premature

Allegra is a relatively new product

A switch of the 2nd generation antihistamines would be
inappropriate, unnecessary, and potentially adverse to
the interest of patient safety

This process today is unprecedented and unwarranted

A switch could have direct and indirect unintended
patient safety and public health implications

Allegra Is Still a Relatively New Product

Allegra launches:
1996:

Allegra 60 mg bid

2000:

Allegra 180 mg qd, Allegra 60 mg tablet

Pediatric use -- Allegra 30 mg

Ongoing clinical development:

Asthma, atopic dermatitis and additional pediatric development
The FDA has asked us to assess unanticipated adverse reactions in
pediatrics
The FDA also asked us to run ECGs on all pediatric patients included
in the trials

Ongoing post-approval safety and effectiveness trials

Ongoing extensive safety monitoring of the post-marketing experience

Seldane:
Over 10 Years on the Market & 24 Million
Patient Years Experience
Marion Merrell Dow was evaluating the OTC switch of Seldane
Neither the company nor the FDA believed there were any significant
safety issues associated with the drug

Signals on drug-drug interactions leading to serious cardiotoxicity

when the drug was not used as labeled

Seldane was withdrawn from the US market before it ever went OTC
Conclusions:
Process, time on the market, and patient exposure are critical
Once a drug is sold OTC, the quality and quantity of adverse
event reports are no longer reliable
A switch would be premature

Unprecedented & Unwarranted

Switch Process
Blue Cross has requested extraordinary action with respect to 3 distinct
drug products

The 3 manufacturers oppose the switch, in part, because of

unanswered potential safety and public health questions

The non-sedating antihistamines are chemically and pharmacologically

different

Traditionally, the manufacturer initiates a switch by filing a

comprehensive NDA supplement. In this case,
No supplement has been filed
No studies have been performed
No actual OTC use or labeling comprehension studies conducted

Limited time and absence of guidance from the FDA

The Switch Could Have Unintended Patient

Health and Safety Consequences
Difficult for patients to accurately diagnose their condition,
identify their triggers, and determine the appropriate
course of treatment

Impact due to misdiagnosis and co-morbidities

Impact on special populations such as pediatrics and the
elderly

Short-term gain as a result of a shift of medication costs to

patients could increase overall healthcare cost
substantially
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The Switch Could Have Unintended Patient

Health and Safety Consequences
The patient, not the doctor, will have to diagnose the
condition

The patient, not the doctor, will have to select what

medications to take and how to take them

The patient, not the insurance company, will have to pay

for the medications

Possible increased use of the less expensive sedating

antihistamines

Blue Cross of California Petition

No evidence that a switch will benefit patient health and safety
Blue Cross argues that the current sedating antihistamines
available OTC are dangerous

Yet, Blue Cross own formulary continues to reserve

non-sedating antihistamines for patients who have failed or
are unable to tolerate over-the-counter therapy
In fact, the FDA has stated that the sedating antihistamines
are safe as currently labeled, and therefore we do not
believe there is a basis for the petition in the first place

Blue Cross argues that patients are being denied access to

non-sedating antihistamines

Liability Concerns
Until we have confidence that a switch will not harm
patients, we are not prepared to subject physicians,
pharmacists, or the company to liability claims based
on a premature entry into the OTC marketplace

In Summary
Shifting the diagnosis responsibility, the treatment

accountability and the cost burden from managed care to

the patients may have direct and indirect patient-safety
and public-health implications

The patients could be playing a costly trial-and-error game

with their health, their quality of life and their money

Allergic rhinitis management could switch from a physician

driven diagnosis and treatment and a reimbursed
medication to a self-diagnosis, a self-chosen treatment
and self payment

There can be no substitute for a reliable process, time on

the market, and patient exposure to characterize rare
adverse events in a timely manner

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FDA Questions
Should fexofenadine be made available for OTC use?
We believe that a switch would be premature

What concerns should be addressed prior to OTC

marketing?
Continue assessing the post-marketing data
Pursue the post-approval clinical trials to further
characterize fexofenadine in a prescription environment
When timely and appropriate, conduct additional
studies to assess the impact of an OTC switch

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Non-Sedating Antihistamines
Rx-to-OTC Switch
NDAC & PADAC Joint Meeting
May 11, 2001
Franois Nader, MD
Senior Vice-President
Medical & Regulatory Affairs, North America
Aventis Pharmaceuticals, Inc.
12

 Switching fexofenadine to OTC would be

premature

There are no compelling reasons to switch

any of the non-sedating antihistamines

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