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Petition to ConvertPetition to Convert Claritin®, Allegra® and Zyrtec® Claritin®, Allegra® and Zyrtec®

to OTC Statusto OTC Status

Robert Seidman, PharmD, MPHChief Pharmacy Officer

WellPoint Health Networks

FDA Pulmonary and OTC

Advisory Committee MeetingMay 11, 2001

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Why I am here before you today. Why I am here before you today.

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HistoryHistory

• 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®

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Status of PetitionStatus 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

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Why Did WellPoint Submit the Petition?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.

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0

100

200

300

400

500

600

700

Pe

rce

nt

Inc

rea

se in

Sa

les

, 1

993

-199

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Antihistamines

(Oral)

Antidepressants

Cholesterol

Reducers

Anti-ulcerants

612%

240%

194%

71%

Recognition of the ProblemRecognition of the Problem

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Why Are These Second Generation Why Are These Second Generation Antihistamines Prescription Drugs?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.

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Second Generation Antihistamines Second Generation Antihistamines Meet Requirements for OTC SwitchMeet 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

Answer - Yes

Answer - Yes

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2nd Generation Antihistamines2nd 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.)

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MethodsMethods• 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:Evidence Report:Efficacy and Toxicity of Selected Efficacy and Toxicity of Selected

11st st and 2and 2nd nd Generation AntihistaminesGeneration Antihistamines

Jack Kern, Pharm.D.Assistant Professor of Clinical Pharmacy

University of Southern California School of Pharmacy

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Meta-Analysis Summary of Global Efficacy

Treated Group (n) ComparisonGroup (n)

Number ofStudies

OverallEffectSize

95%Confidence

Interval

p value

Cetirizine 10 mg (384) Placebo (378) 7 0.24 0.17-0.31 <0.001Loratadine 10 mg (746) Placebo (744) 11 0.21 0.16-0.26 <0.001Cetirizine (Children)(193)

Placebo (197) 3 0.26 0.16-0.36 <0.001

Cetirizine 10 mg Loratadine 10 mg 3 0.15 0.05-0.25 <0.05Chlorpheniramine (199) Terfenadine (203) 5 0.05 -.02-0.12 >0.05

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Meta-Analysis Summary of Sedation

Treated Group (n) ComparisonGroup (n)

Number ofStudies

OverallEffectSize

95%Confidence

Interval

p value

Chlorpheniramine (219) Placebo (217) 6 0.17 0.1-0.24 <0.001Cetirizine 10 mg (766) Placebo (756) 9 0.06 0.01-0.11 <0.05Cetirizine (Children) (163) Placebo (160) 3 0.05 0.01-0.09 <0.02Loratadine 10 mg (727) Placebo (714) 11 0.0 -.02-0.02 >0.05

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ConclusionsConclusions

• The quality of these studies is high

• 2nd generation antihistamines are as effective as the 1st generation products

• 2nd generation antihistamines are safer than the 1st generation products

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Cost-Effectiveness of Converting Non-Sedating Cost-Effectiveness of Converting Non-Sedating Antihistamines from Rx to OTC StatusAntihistamines 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

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Base Case ResultsBase 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

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ICER Sensitivity Analysis:ICER Sensitivity Analysis:Percent Drop in Non-Sedating Price After OTC ConversionPercent Drop in Non-Sedating Price After OTC Conversion

-80,000

-60,000

-40,000

-20,000

0

20,000

40,000

60,000

80,000

100,000

0 20 40 60 80

Percent

Cost/QALY

$50K/QALY breakeven point: 27.5% drop

Base Case

66% Drop

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ICER Sensitivity Analysis:ICER Sensitivity Analysis:Percent of Patients Treated by MDPercent of Patients Treated by MD

-300,000

-250,000

-200,000

-150,000

-100,000

-50,000

0

5 12 15 20 25 30 35

Percent

Cost/QALY

Base Case:

12% Treated

by MD

Base Case:12% Treated

by MD

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ConclusionsConclusions

• 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

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Precedent for an FDA Initiated OTC SwitchPrecedent 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

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OTC Status of Second Generation OTC Status of Second Generation Antihistamines is in the Public InterestAntihistamines 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

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ExampleExample: Draft Labeling - : Draft Labeling - Loratadine OTCLoratadine 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.

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WellPoint’s Request for WellPoint’s Request for the Advisory Committee, FDA and the Industrythe 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