1. 1 Robert J. Spiegel, M.D. Sr. V. P. Medical Affairs Chief Medical Officer Schering Plough FDA ADVISORY COMMITTEE 5/11/01

2. 2 OVERVIEW For many patients, allergies are not appropriately treated without physician management More data are necessary to support this OTC switch based on unique issues of use OTC status will decrease access for many patients, and may not decrease use of first-generation anti-histamines

3. 3 OVERVIEW For many patients, allergies are not appropriately treated without physician management Different types of antihistamine users Short-term vs. chronic Comorbid diseases Cold Use vs. Allergy Disease Management

4. 4 OVERVIEW For many patients, allergies are not appropriately treated without physician management More data are necessary to support this OTC switch based on unique issues of use OTC status will decrease access for many patients, and may not decrease use of first-generation antihistamines

5. 5 “Data to support the OTC switch generally comes from the following sources: efficacy trials, safety data, actual use trials, and label comprehension trials…these latter two trials may or may not be needed depending upon whether there are any unique issues related to use, warnings, or directions that need to be tested prior to marketing.” “The switch of a prescription drug to OTC marketing requires a review of the post-marketing safety data and a determination that a consumer can adequately use the product in an OTC setting” FDA OTC Antihistamine Review Team 4/5/01

6. 6 OVERVIEW For many patients, allergies are not appropriately treated without physician management More data are necessary to support this OTC switch based on unique issues of use OTC status will decrease access for many patients, and may not decrease use of first-generation antihistamines

7. 7 For many patients, allergies are not appropriately treated without Physician Management 1. Prescription status may be necessary to protect and optimize public health

8. 8 U.S. Health Care System - 2001 - Evidence-based medicine - Guideline-driven practice - Disease management approach

9. 9 U.S. Health Care System Allergy Management - 2001 –Diagnostic Evaluation Differentiate allergic disorders from other diseases Uncover previously unsuspected allergens Assess comorbid conditions – Environmental Assessment – Antigen Testing –Pharmacologic Therapy Antihistamines +Rx for Comorbid Conditions Decongestants Nasal Steroids Immunotherapy –Follow-up, Reassessment, Compliance Management

10. 10 For many patients allergies are not appropriately treated without Physician Management 1.Prescription status may be necessary to protect and optimize public health 2.The safety profiles of the second- generation antihistamines in an OTC setting are not fully known

11. 11 2. The safety profiles of the second- generation antihistamines in an OTC setting are not fully known –How often will they be used to treat colds? –How often will patients dose incorrectly? –How many patients will experience exacerbation of untreated or unrecognized co-morbidities? –How often will patients have adverse outcomes as a result of delays in seeking medical care?

12. 12 For many patients allergies are not appropriately treated without Physician Management 1.Prescription status may be necessary to protect and optimize public health 2.The safety profiles of the second- generation antihistamines in an OTC setting are not fully known 3.Allergies are frequently chronic, complex diseases with serious co-morbidities

13. 13 Allergies are frequently chronic, complex diseases with Serious Comorbidities Co-morbid conditions associated with allergic rhinitis –Asthma –Sinusitis –Otitis Media Children are seriously affected by allergic rhinitis –10-40% of school children –Under treatment is related to learning and behavioral problems

14. 14 Allergies: >50 million Americans Asthma: 15 million Americans 4.8 million children Asthma Prevalence  75% 1980--> 1994 Asthma Deaths 1980 - 11.5/1 million 1995 - 18.0/1 million (5,500 deaths)

15. 15 Allergic Rhinitis and Asthma Often Co-exist 78% of asthma patients have nasal symptoms 38% of allergic rhinitis patients have asthma 3 million Claritin® Rx’s are co-prescribed with R x ’s for asthma medications (for approximately 1.2M patients with asthma)

16. 16 Allergy-Asthma Link Treating allergic inflammation in the nose can reduce asthma symptoms and lower airway hyper-responsiveness. 1,2 Asthmatic patients with Allergic Rhinitis have higher medical costs In a longitudinal study of 783 students: 3 –Resolution of Allergic Rhinitis symptoms correlated with improvement in asthma (p=.0078) –Worsening of Allergic Rhinitis was associated with persistence of asthma 1 Allergy Clin Immonol 1995;95:923-32 2 Allergy Clin Immonol 1996;98:274-82 3 Allergy Proc 1994;15:21-25.

17. 17 CHANGES IN ALLERGY MANAGEMENT FIRST-GENERATION ANTIHISTAMINES Short-term/episodic use Simple Sx relief for simple allergy patients ?co-morbidity Frequent use in colds SECOND-GENERATION ANTIHISTAMINES Long-Term/chronic use Disease management for Complex patients Frequent co-morbidity Not effective for colds

18. 18 OTC status may decrease access and not decrease use of first-generation antihistamines Medicaid and poor patients will be unable to afford 2nd-Generation products as OTC’s Patients currently with insurance coverage will make decisions based on out-of-pocket costs Use of sedating antihistamines may well increase

19. 19 US and Canadian Antihistamine Market Share Source: IMS Health NPA Plus and A.C. Nielsen Note: Calculated using maximum dose per day.

20. 20 CONCLUSION Loratadine is most appropriately used as an Rx product There are unique issues related to use 1st Generation  2nd Generation FDA Switch Principles -Labeling must be developed and tested -Actual Use Trials are necessary

21. 21 CONCLUSION Loratadine is most appropriately used as an Rx product There are unique issues related to use 1st Generation  2nd Generation FDA Switch Principles -Labeling must be developed and tested -Actual Use Trials are necessary

22. 22 CONCLUSION Loratadine is most appropriately used as an Rx product There are unique issues related to use 1st Generation  2nd Generation FDA Switch Principles -Labeling must be developed and tested -Actual Use Trials are necessary

23. 23 CONCLUSION Loratadine is most appropriately used as an Rx product There are unique issues related to use 1st Generation  2nd Generation FDA Switch Principles -Labeling must be developed and tested -Actual Use Trials are necessary

24. 24 ISSUES REQUIRING ASSESSMENT FOR OTC SWITCH Ability to self-diagnose the condition Assessment of risk of initial misdiagnosis Assessment of risk of subsequent misdiagnosis of disease exacerbation or common co-morbid conditions Assessment of risk of incorrect dosing (voluntary and/or inadvertent) Assessment of safety in at-risk populations Label development and comprehension

25. 25 CONCLUSION Loratadine is most appropriately used as an Rx product There are unique issues related to use 1st Generation  2nd Generation FDA Switch Principles -Labeling must be developed and tested -Actual Use Trials are necessary

26. 26 R x OTC Benefit/ Risk + ?

27. 27 Benefit/ Risk R x OTC Benefit/ Risk +

28. 28 QUESTIONS