1. 1 Petition to Convert Claritin®, Allegra® and Zyrtec® to OTC Status Robert Seidman, PharmD, MPH Chief Pharmacy Officer WellPoint Health Networks FDA Pulmonary and OTC Advisory Committee Meeting May 11, 2001

2. 2 Why I am here before you today.

3. 3History Blue Cross of California, a subsidiary of WellPoint Health Networks –Filed a Citizen Petition with FDA on July 22, 1998 under 21 CFR 10.30 –Requesting that 2nd generation antihistamines and antihistamine/decongestant combinations be switched to over-the-counter status –Claritin®, Claritin-D® –Allegra®, Allegra-D® –Zyrtec®

4. 4 Status of Petition No FDA decision –Petition pending for almost 3 years January 1999 –FDA letter from Dr. Woodcock –Petition presents complex issues –FDA needs more time to evaluate June 2000 –FDA hearing to review Rx to OTC process May 2001 –FDA hearing to discuss the WellPoint petition

5. 5 Why Did WellPoint Submit the Petition? Patients are seeking greater ownership and control over their healthcare; Prefer to self-medicate where appropriate and feasible; More convenient for patients; Patients can decide when they need to use antihistamines and antihistamine/decongestant combinations; Already over 100 different antihistamines and antihistamine/decongestant combinations OTC; and Rising cost of Rx drugs is making it difficult to provide an affordable, broad-based prescription benefit.

6. 6 Percent Increase in Sales, 1993-1998 Antihistamines (Oral) Antidepressants Cholesterol Reducers Anti-ulcerants 612% 240% 194% 71% Recognition of the Problem

7. 7 Why Are These Second Generation Antihistamines Prescription Drugs? Durham-Humphrey Amendment to Federal Food, Drug and Cosmetic Act (1951) A drug is expected to be made available without a prescription if, by following the labeling, consumers can use it safely and effectively without professional guidance.

8. 8 Second Generation Antihistamines Meet Requirements for OTC Switch Can the condition be adequately self diagnosed? Can the condition be successfully self-treated? Is the self-treatment product safe and effective for consumer use, under conditions of actual use? Answer - Yes

9. 9 2nd Generation Antihistamines Effective for relieving symptoms –Runny nose, sneezing, itching of the nose or throat and itchy, watery eyes Less side effects than 1st generation antihistamines currently available OTC –Less sedation (drowsiness) –Less anticholinergic effects (dizziness, blurred vision, dry mouth, etc.)

10. 10 Methods Literature –Identify all RCTs with selected antihistamines (reference librarian) –Reject/accept references –Screen titles, abstracts and references Build evidence tables –Significant factors! Build shrinkage plots (statistician) Discussion and understanding Evidence Report: Efficacy and Toxicity of Selected 1 st and 2 nd Generation Antihistamines Jack Kern, Pharm.D. Assistant Professor of Clinical Pharmacy University of Southern California School of Pharmacy

11. 11 Meta-Analysis Summary of Global Efficacy

12. 12 Meta-Analysis Summary of Sedation

13. 13 Conclusions The quality of these studies is high 2 nd generation antihistamines are as effective as the 1 st generation products 2 nd generation antihistamines are safer than the 1 st generation products

14. 14 Cost-Effectiveness of Converting Non-Sedating Antihistamines from Rx to OTC Status Michael B. Nichol, Ph.D., Patrick Sullivan, Ph.D. (cand.) University of Southern California School of Pharmacy Decision-analytic model Perspective: Societal Period: One year Cohort: Adult population in the U.S. Comparison: Prescription loratadine vs. over-the- counter loratadine Impact: Effects of sedation on motor vehicle accidents Output: Incremental cost per quality-adjusted life year

15. 15 Base Case Results The Incremental Cost-Effectiveness Ratio (ICER) for the base case analysis is a savings of more than $62,000 per quality-adjusted life year Using the same base case values, an alternative estimate produced a savings of more than $98,000 per life year saved

16. 16 ICER Sensitivity Analysis: Percent Drop in Non-Sedating Price After OTC Conversion Percent Cost/QALY $50K/QALY breakeven point: 27.5% drop Base Case 66% Drop

17. 17 ICER Sensitivity Analysis: Percent of Patients Treated by MD Percent Cost/QALY Base Case: 12% Treated by MD Base Case: 12% Treated by MD

18. 18 Conclusions Preliminary evidence suggests that converting non-sedating antihistamines to over-the-counter status would be cost-saving to society as a result of reductions in motor vehicle accidents Additional factors should be incorporated into a final model: –Inappropriate treatment with OTC non-sedating antihistamines –Modeling effect of OTC availability on price and demand –Refining incremental QALY improvements due to availability of non-sedating antihistamine –Impact on workplace productivity

19. 19 Precedent for an FDA Initiated OTC Switch FDA initiated the OTC switch of Alupent® (metaproterenol) inhaler in 1982 FDA did not seek input from an expert advisory panel or the public before permitting the drug to be marketed as an OTC drug product FDA received comments and public criticism from physicians who felt they should have been consulted prior to the switch FDA reiterated that it believed Alupent® to be safe for OTC use, but switched the drug back to Rx status

20. 20 OTC Status of Second Generation Antihistamines is in the Public Interest The products meet all requirements for OTC status Long history of OTC marketing around the world Drugs are effective and safe –Lower incidence of side effects than existing OTC antihistamine products Switching the products to OTC status will make safer products accessible to the public

21. 21 Example: Draft Labeling - Loratadine OTC INDICATIONS : For the temporary relief of sneezing, itchy, watery eyes, itching of the nose or throat and runny nose due to hay fever or other upper respiratory allergies. DIRECTIONS: ADULTS AND CHILDREN 6 YEARS AND OVER One tablet once daily. Do not exceed recommended dosage. Prolonged usage should only be on the advice of a physician. WARNINGS : If you are pregnant or nursing a baby seek the advice of a health care professional before using this product. KEEP THIS AND ALL OTHER DRUGS OUT OF THE REACH OF CHILDREN. In case of accidental overdose, seek professional assistance or contact a Poison Control Center immediately.

22. 22 WellPoint’s Request for the Advisory Committee, FDA and the Industry Advisory Committee –Vote today to recommend OTC status FDA – Act swiftly to switch the products to OTC status Industry –Work with the Agency to make these safe and effective second generation antihistamines readily available to the U.S. public