Non-Sedating Antihistamines Rx-to-OTC Switch NDAC & PADAC Joint Meeting

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

2. 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

3. 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 ECG’s on all pediatric patients included in the trials • Ongoing post-approval safety and effectiveness trials • Ongoing extensive safety monitoring of the post-marketing experience

4. 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Signals on drug-drug interactions leading to serious cardiotoxicity when the drug was not used as labeled • Seldane was withdrawn from the US market before it ever went OTC • Conclusions: • Process, time on the market, and patient exposure are critical • Once a drug is sold OTC, the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

5. Unprecedented & UnwarrantedSwitch 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

6. 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

7. 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

8. 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

9. 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

10. 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

11. 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

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

13. Switching fexofenadine to OTC would be premature • There are no compelling reasons to switch any of the non-sedating antihistamines