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UPDATES

• BPCA - Enacted January 4, 2002

• Pediatric Rule - In effect

• Pediatric Rule Statistics

• Exclusivity Statistics

• Reorganization

Pediatric Initiatives• Pediatric Rule (1998)

- FDA’s 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

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

Applications 404

Waivers (partial/complete) 195

Complete Waivers130

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

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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

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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

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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 <2 years of age for 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 <12 years of age; HPA axis 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 <12 years of age;

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 <17 years of age; HPA axis suppression

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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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N ew O rgan iz atio nO cto b er 2002

*Ju n e 2 0 0 2

O D E I O D E II O D E III O D E IV O D E V O ffice of Ped iatric Dru gDevelop m en t &

Prog ram In itiatives*

O ffice o f N ew D ru g s

C en te r fo r D ru g s*

F D A

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Additional Information

Internet: http://www.fda.gov/cder/pediatric

Peds Line:

(301) 594-7337

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