1. 1 One Year Post-Exclusivity Adverse Event Review: Meloxicam Pediatric Advisory Committee Meeting November 16, 2006 Hari Cheryl Sachs, MD, FAAP Medical Officer Pediatric and Maternal Health Staff Office of New Drugs Center for Drug Evaluation and Research Food and Drug Administration

2. 2 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

3. 3 Background Drug Information Indication: relief of the signs and symptoms of: – osteoarthritis and rheumatoid arthritis (adults) –Pauciarticular or polyarticular course Juvenile Rheumatoid Arthritis (children > 2 years) Dosage: –Adults: 7.5 to 15 mg once daily –Children: 0.125 mg/kg (max 7.5 mg) once daily

4. 4 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by 21 % 1 –84.7 million (May 2004 to Apr 2005) to 66.9 million (May 2005 to Apr 2006) –Valdecoxib and rofecoxib withdrawn (Sept 2004 and April 2005 respectively) –Retail prescriptions (but not over-the-counter products sales) of ibuprofen and naproxen included Dispensed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 drugs 1 –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 osteochondrosis 3 1 Verispan LLC, Vector One®: National (VONA). Data extracted June 2006. Nine NSAIDs: celecoxib, ibuprofen, indomethacin, meloxicam, naproxen, oxaprozin, rofecoxib, tolmetin, and valdecoxib. 2 Verispan LLC, Vector One®: National (VONA). Data extracted June 2006 3 Verispan LLC, Vector One®: Physician Drug & Diagnosis Audit. Data extracted June 2006

5. 5 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 (> 2 years)

6. 6 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

7. 7 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 Bell’s 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?

8. 8 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