Robert J. Spiegel, M.D.

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

• Data to support the OTC switch generally
  comes from the
• following sources efficacy trials, safety
  data, actual use trials, and label comprehension
  trialsthese 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

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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
For many patients, allergies are not
appropriately treated without Physician Management

• 1. Prescription status may be necessary to
  protect and optimize public health

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U.S. Health Care System - 2001

• - Evidence-based medicine
• - Guideline-driven practice
• - Disease management approach

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U.S. Health Care SystemAllergy 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

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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

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• 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?

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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

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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

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• Allergies gt50 million Americans
• Asthma 15 million Americans
• 4.8 million children
• Asthma Prevalence
• ?75 1980--gt 1994
• Asthma Deaths
• 1980 - 11.5/1 million
• 1995 - 18.0/1 million
• (5,500 deaths)

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Allergic Rhinitis and Asthma Often Co-exist

• 78 of asthma patients have nasal symptoms
• 38 of allergic rhinitis patients have asthma
• 3 million Claritin Rxs are co-prescribed with
  Rxs for asthma medications (for
  approximately 1.2M patients with asthma)

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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 students3
• 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 199595923-32
• 2 Allergy Clin Immonol 199698274-82
• 3 Allergy Proc 19941521-25.

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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

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• 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 OTCs
• Patients currently with insurance coverage will
  make decisions based on out-of-pocket costs
• Use of sedating antihistamines may well increase

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US and CanadianAntihistamine Market Share

Source IMS Health NPA Plus and A.C.
Nielsen Note Calculated using maximum dose per
day.
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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

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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

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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
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

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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

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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

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R
OTC
x
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R
OTC
x
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QUESTIONS