Transcript Petition to Convert Claritin®, Allegra® and Zyrtec® to OTC Status

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
1
Why I am here before you today.
2
History
• 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®
3
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
4
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.
5
Recognition of the Problem
Percent Increase in Sales,
1993-1998
700
600
500
400
300
200
100
0
6
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.
7
Second Generation Antihistamines
Meet Requirements for OTC Switch
• Can the condition be adequately
self diagnosed?
Answer - Yes
• Can the condition be successfully
self-treated?
Answer - Yes
• Is the self-treatment product safe and
effective for consumer use, under
conditions of actual use? Answer - Yes
8
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.)
9
Evidence Report:
Efficacy and Toxicity of Selected
1st and 2nd Generation Antihistamines
Jack Kern, Pharm.D.
Assistant Professor of Clinical Pharmacy
University of Southern California School of Pharmacy
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
10
Meta-Analysis Summary of Global Efficacy
Treated Group (n)
Cetirizine 10 mg (384)
Loratadine 10 mg (746)
Cetirizine (Children)
(193)
Cetirizine 10 mg
Chlorpheniramine (199)
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Comparison
Group (n)
Number of
Studies
Placebo (378)
Placebo (744)
Placebo (197)
7
11
3
Overall
Effect
Size
0.24
0.21
0.26
Loratadine 10 mg
Terfenadine (203)
3
5
0.15
0.05
95%
Confidence
Interval
0.17-0.31
0.16-0.26
0.16-0.36
p value
0.05-0.25
-.02-0.12
<0.05
>0.05
<0.001
<0.001
<0.001
Meta-Analysis Summary of Sedation
Treated Group (n)
Chlorpheniramine (219)
Cetirizine 10 mg (766)
Cetirizine (Children) (163)
Loratadine 10 mg (727)
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Comparison
Group (n)
Placebo (217)
Placebo (756)
Placebo (160)
Placebo (714)
Number of
Studies
6
9
3
11
Overall
Effect
Size
0.17
0.06
0.05
0.0
95%
Confidence
Interval
0.1-0.24
0.01-0.11
0.01-0.09
-.02-0.02
p value
<0.001
<0.05
<0.02
>0.05
Conclusions
• 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
13
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-thecounter loratadine
• Impact: Effects of sedation on motor vehicle accidents
• Output: Incremental cost per quality-adjusted life year
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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
15
ICER Sensitivity Analysis:
Percent Drop in Non-Sedating Price After OTC Conversion
Cost/QALY
100,000
80,000
60,000
40,000
20,000
Base Case
0
66% Drop
$50K/QALY
breakeven point:
27.5% drop
-20,000
-40,000
-60,000
-80,000
0
20
40
Percent
16
60
80
ICER Sensitivity Analysis:
Percent of Patients Treated by MD
Cost/QALY
0
-50,000
-100,000
-150,000
BaseCase:
Case:
Base
-200,000
12%
Treated
12% Treated
by MD
by MD
-250,000
-300,000
5
12
15
Percent
17
20
25
30
35
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
18
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
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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
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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.
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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
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