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One Year Post-Exclusivity Adverse Event Review:

Meloxicam

Pediatric Advisory Committee Meeting November 16, 2006

Hari Cheryl Sachs, MD, FAAPMedical OfficerPediatric and Maternal Health StaffOffice of New DrugsCenter 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 > 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– Valdecoxib and rofecoxib withdrawn (Sept 2004 and April 2005 respectively)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 osteochondrosis31Verispan 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 20063Verispan LLC, Vector One®: Physician Drug & Diagnosis Audit. Data extracted June 2006

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Pediatric Exclusivity Labeling Changes: Meloxicam

Clinical Pharmacology: Special Populations- PediatricGeneral trend lower exposure in younger patients (2 to 6

years), compared to older patients (7 to 16 years)Half-life slightly longer in younger patientsWeight (not age) predictor of clearance

Clinical TrialsTwo 12-week, double-blind, parallel arm, active-

controlled trials are describedIndications

Indicated for relief of signs and symptoms of JRA (> 2 years)

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Pediatric Exclusivity Labeling Changes: Meloxicam

Precautions: Pediatric UseSafety and effectiveness for pediatric JRA patients (2 to

17 years) evaluated in 3 clinical trialsAdverse 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 AdministrationWeight 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 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?

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Acknowledgements

OSE

Gita Akhavan-Toyserkani

Andrea Feight

Laura Governale

Solomon Iyasu

Rosemary Johann-Liang

Carol Pamer

DAARPSharon HertzTatiana OussovaJeff Siegel

PMHSLisa MathisKristin PhucasJean Temeck