UPDATES

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UPDATES

• BPCA - Enacted January 4, 2002
• Pediatric Rule - In effect
• Pediatric Rule Statistics
• Exclusivity Statistics
• Reorganization

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Pediatric Initiatives

• Pediatric Rule (1998)
• - FDAs legal authority to require studies in
  pediatric patients has been challenged by the
  Association of American Physicians and surgeons,
  the Competitive Enterprise Institute and Consumer
  Alert
• - HHS Secretary announced that FDA will continue
  to defend the Pediatric Rule in court and not
  pursue a stay of litigation (April 19, 2002).
• - THE PEDIATRIC RULE REMAINS IN EFFECT

3
Pediatric Rule Update4/1/99 - 3/31/02

• Applications 404
• Waivers (partial/complete) 195
• Complete Waivers 130
• Deferrals 172
• Completed Studies 94

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Pediatric Rule Update4/1/99 - 3/31/02

• Reason for Deferrals
• Do not want to hold up the adult approval
• Desire for additional data before proceeding to
  younger age groups
• Reason for Waivers
• Safety issue
• Small 's of patients
• OTC indication- not self-diagnosable
• Adult indication- not applicable to pediatrics
• Fixed combinations
• Not a meaningful therapeutic benefit/substantial
  number
• Literature information supports pediatric
  labeling

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Pediatric Rule Update4/1/99 - 3/31/02 Examples
of Indications/Diseases Waived

• Osteoporosis
• Reduction of facial hair in women
• Acne vulgaris (0-11yr)
• HIV infection (fixed-dose combination)
• Facial wrinkles

• Actinic keratosis
• MI/stroke/angina
• Parkinson's disease
• Dementia of Alzheimers

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Pediatric Rule Update4/1/99 - 3/31/02 Examples
of Indications/Diseases Waived

• Sleep disorder
• Prostate cancer
• Post-menopausal breast cancer
• Colorectal Polyps
• Advanced ovarian cancer

• Fertility
• BPH
• Abortifacient
• Vaginal candidiasis (0-12yr)
• COPD

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Applications Subject to the Rule and Exclusivity
Granted

• Abacavir Didanosine
• Ammonium lactate Enalapril
• Atorvastatin Etodolac
• Azelastine Famotidine
• Brimonidine Fluoxetine
• Buspirone Gabapentin
• Calcitriol Ibuprofen
• Cetirizine Ibuprofen/Pseud
• Cromolyn Insulin glargine

8
Applications Subject to the Rule and Exclusivity
Granted

• Lamivudine Propofol
• Loratadine Remifentanil
• Lovastatin Ribavirin/Intron A
• Metformin Sertraline
• Mometsone Sevoflurane
• Montelukast Simvastatin
• Nevirapine Sotalol
• Pemirolast Stavudine
• Pimecrolimus Tramadol

9
Pediatric Exclusivity Statsas of 6/1/02

• Proposed Pediatric Study Requests 310
• Written Requests 246
• Exclusivity Determinations 66
• Exclusivity Granted 58
• Exclusivity Denied 8
• Drugs Labeled 36

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Pediatric Exclusivity Statsas of 6/1/02

• Types of Studies
• Efficacy 201 34
• PK Safety 175 30
• PK/PD 56 10
• Safety 97 17
• Other 51 9
• 580 studies requested
• 33,449 projected total of patients

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Labeled Products

• Ibuprofen - Motrin
• Ibuprofen - Advil
• Midazolam
• Abacavir
• Ranitidine
• Insulin glargine
• Pemirolast
• Azelastine
• Lovastatin

• Oxaprozin
• Lamivudine - HBV
• Pimecrolimus
• Brimonidine
• Buspirone
• Ibuprofen/pseudoephe-drine
• Sotalol
• Ketorolac

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Labeled Products

• Ammonium lactate
• Etodolac
• Fluvoxamine
• Sevoflurane
• Atovaquone/proguanil
• Betamethasone
• Ribavirin/Intron A
• Gabapentin
• Loratadine

• Metformin
• Enalapril
• Propofol
• Cromolyn
• Calcitriol
• Didanosine
• Stavudine
• Isotretinoin
• Famotidine

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Labeled Products with Significant Changes for
Dosing or Risk

• Midazolam (Versed) Sedation/anxiolysis/amnesia-
  higher risk of serious life-threatening
  situations in children with congenital heart
  disease and pulmonary hypertension and identified
  need to begin therapy at lower end of dosing
  range in this subpopulation to prevent
  respiratory compromise
• Etodolac (Lodine) JRA sign/symptom relief
  (6yr-16yr)
• -higher dose (per kg basis) needed in younger
  children approximately 2 times the lower dose
  recommended in adults for effective treatment
• Fluvoxamine (Luvox) Rx of OCD - higher doses in
  adolescents than previously recommended girls
  ages 8-11 years may require lower doses.

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Labeled Products with Significant Changes for
Dosing or Risk

• Gabapentin (Neurontin) - adjunctive Rx in
  partial seizures - higher doses required in
  children less than 5 years of age in order to
  control seizures new adverse events (e.g.
  hostility and aggression) identified in children
  less than 12 years
• Propofol (Diprivan) -induction and/or
  maintenance of anesthesia - increased mortality
  when used for pediatric ICU sedation over
  standard sedative agents (9 vs. 4) serious
  bradycardia when propofol is concomitantly
  administered with fentanyl
• Sevoflurane (Ultane) induction and maintenance
  of general anesthesia - rare cases of seizures
  reported in children without a previous seizure
  history

15
Labeled Products with Significant Changes for
Dosing or Risk

• Ribavirin/Intron A (Rebetron) increased
  incidence of suicidal ideation or attempts among
  pediatric patients as compared with adults (2.4
  vs. 1) decreased rate of linear growth and
  weight gain during therapy, with general reversal
  in the post treatment period
• Pimecrolimus (Elidel) - indicated for short-term
  and intermittent long-term therapy in
  mild-moderate atopic dermatitis in
  non-immunocompromised patients 2years of age
  (NOT RECOMMENDED in patients safety concerns including infections, pyrexia,
  and diarrhea)

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Labeled Products with Significant Changes for
Dosing or Risk

• Betamethasone (Diprolene AF) Corticosteroid
  responsive dermatoses NOT RECOMMENDED in
  pediatric patients suppression local adverse reactions, including
  signs of skin atrophy in 10 of patients 3 mo-12
  yrs of age
• Betamethasone (Diprosone Cream, Ointment,
  Lotion)
• NOT RECOMMENDED in patients HPA axis suppression local adverse reactions
  included signs of skin atrophy (telangectasia,
  bruising, shininess) in cream ointment but not
  lotion
• Betamethasone (Lotrisone) NOT RECOMMENDED in
  patients

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Labeled Product with Safety and Effectiveness
Issue

• Buspirone (Buspar)
• - Safety and effectiveness were NOT established
  in patients 6-17 years of age for treatment of
  
• General Anxiety Disorder at doses recommended
• for adults
• - AUC and Cmax of buspirone and active
  metabolite were equal to or higher in
  children and adolescents as compared with adult
  PK parameters

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Additional Information

• Internet
• http//www.fda.gov/cder/pediatric
• Peds Line
  
• [phone]
  
• 
  
• 
  

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