One Year Post-Exclusivity Adverse Event Review: Meloxicam Pediatric Advisory Committee Meeting November 16, 2006

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One Year Post-Exclusivity Adverse Event
ReviewMeloxicam Pediatric Advisory Committee
Meeting November 16, 2006
Hari Cheryl Sachs, MD, FAAP Medical
Officer Pediatric and Maternal Health
StaffOffice of New Drugs Center for Drug
Evaluation and Research Food and Drug
Administration
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Background Drug Information

• Drug Mobic (meloxicam)
• Therapeutic Category Nonsteroidal
  anti-inflammatory
• Sponsor Boehringer Ingelheim
• Original Market Approval April 13, 2000
• Pediatric Exclusivity Granted April 15, 2005
• Mechanism of Action related to prostaglandin
  synthetase (cyclo-oxygenase) inhibition

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Background Drug Information

• Indication relief of the signs and symptoms of
• osteoarthritis and rheumatoid arthritis (adults)
• Pauciarticular or polyarticular course Juvenile
  Rheumatoid Arthritis (children gt 2 years)
• Dosage
• Adults 7.5 to 15 mg once daily
• Children 0.125 mg/kg (max 7.5 mg) once daily

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Drug Use Trends (Outpatient Settings) Meloxicam

• Dispensed retail prescriptions for group of 9
  NSAIDs (including meloxicam) decreased by 21 1
• 84.7 million (May 2004 to Apr 2005) to 66.9
  million (May 2005 to Apr 2006)
• Valdecoxib and rofecoxib withdrawn (Sept 2004 and
  April 2005 respectively)
• Retail prescriptions (but not over-the-counter
  products sales) of ibuprofen and naproxen
  included
• Dispensed prescriptions for meloxicam ranked
  fourth among the 9 nonsteroidal anti-inflammatory
  drugs1
• Estimated 7.4 million (11 ) (May 2005 to April
  2006)
• Pediatric use 0.3 (approximately 21,000
  prescriptions from May 2005 to April 2006)2
• Diagnosis Ankle sprains, juvenile
  osteochondrosis3
• 1Verispan LLC, Vector One National (VONA).
  Data extracted June 2006.
• Nine NSAIDs celecoxib, ibuprofen,
  indomethacin, meloxicam, naproxen, oxaprozin,
  rofecoxib, tolmetin, and valdecoxib.
• 2Verispan LLC, Vector One National (VONA).
  Data extracted June 2006
• 3Verispan LLC, Vector One Physician Drug
  Diagnosis Audit. Data extracted June 2006

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Pediatric Exclusivity Labeling Changes Meloxicam

• Clinical Pharmacology Special Populations-
  Pediatric
• General trend lower exposure in younger patients
  (2 to 6 years), compared to older patients (7 to
  16 years)
• Half-life slightly longer in younger patients
• Weight (not age) predictor of clearance
• Clinical Trials
• Two 12-week, double-blind, parallel arm,
  active-controlled trials are described
• Indications
• Indicated for relief of signs and symptoms of JRA
  (gt 2 years)

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Pediatric Exclusivity Labeling Changes Meloxicam

• Precautions Pediatric Use
• Safety and effectiveness for pediatric JRA
  patients (2 to 17 years) evaluated in 3 clinical
  trials
• Adverse Reactions
• Safety database 378 patients dosed 0.125 to
  0.375 mg/kg/day up to 24 weeks (efficacy) and 1
  year (efficacy and pk studies)
• Although adverse events similar between adults
  and children, abdominal pain, vomiting, diarrhea,
  headache and pyrexia more common in children
• Dosage and Administration
• Weight based dosing is included

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Summary Meloxicam

• No pediatric AEs identified during one-year
  exclusivity period
• Since approval, 5 pediatric AEs- either labeled
  events or confounded, with exception of one case
  of Bells palsy
• This completes the one-year post-exclusivity AE
  reporting as mandated by BPCA
• FDA recommends routine monitoring of meloxicam
  for AEs in all populations.
• Does the Advisory Committee concur?

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Acknowledgements

• OSE
• Gita Akhavan-Toyserkani
• Andrea Feight
• Laura Governale
• Solomon Iyasu
• Rosemary Johann-Liang
• Carol Pamer

• DAARP
• Sharon Hertz
• Tatiana Oussova
• Jeff Siegel
• PMHS
• Lisa Mathis
• Kristin Phucas
• Jean Temeck