One Year Post Exclusivity Adverse Event Review Update: Orlistat Pediatric Advisory Committee Meeting

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One Year Post Exclusivity Adverse Event Review
UpdateOrlistat Pediatric Advisory Committee
Meeting April 11, 2007
Hari Cheryl Sachs, MD, FAAPMedical
Officer Pediatric and Maternal Health
Staff Office of New Drugs Food and Drug
Administration
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PAC Meeting February 2005 Conclusions Orlistat

• Minimal use in pediatric patients
• Insufficient events to draw any conclusions
• Reports of cholelithiasis during trial and
  post-marketing surveillance (relationship to
  therapy vs. underlying obesity and rapid weight
  loss unclear)
• FDA recommended continued monitoring of AEs,
  particularly for the risk of cholelithiasis, for
  this drug in all populations.

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Background Drug Information

• Drug Xenical (orlistat)
• Therapeutic Category lipase inhibitor
• Sponsor Roche
• Original Market Approval April 23, 1999
• Pediatric Exclusivity Granted September 12, 2003
• OTC switch (adults only) February 7, 2007
• Mechanism of action inhibits absorption of
  dietary fats

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Background Drug Information

• Orlistat Rx (Xenical)
• Indication (gt 12 years of age)
• Obesity management in conjunction with weight
  loss
• Body Mass Index (BMI) gt 30 mg/m2 or 27 mg/m2 with
  risk factors (hypertension, diabetes,
  dyslipidemia)
• Dosage 120 mg TID
• Orlistat OTC (Alli)
• Indication (gt 18 years of age)
• Weight loss in adults when used with reduced
  calorie and low-fat diet
• Dosage 60 mg TID with meals containing fat

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Outpatient Drug Use Trends Orlistat

• Dispensed prescriptions for all age groups have
  continued to decrease from 1.6 million (Oct
  2001- Sept 2002) to 547,000 (Oct 2005- Sept
  2006).1
• Orlistat is prescribed mainly in adults.2
• Pediatric patients (ages 1-16) account for lt1
  of prescriptions annually.2
• 1Verispan, LLC, Vector One National (VONA) Data
  extracted 1-12-2007
• 2Verispan, Total Patient Tracker, data extracted
  1-18-2007

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Cholelithiasis Orlistat

• Adverse Events cholelithiasis/acute
  cholecystitis (April 1999 through Dec 2006)
• Domestic cases (all ages) 37
• Pediatric cases one, previously described
• No additional pediatric cases since Feb 2005
• Conclusion
• Some concern re possible association between
  cholelithiasis and orlistat use in all
  populations
• No safety concern specific to pediatrics

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Labeling Change Orlistat Jan 2007
Precautions General Substantial weight loss can
increase risk of cholelithiasis Clinical trial
of type 2 Diabetes prevention orlistat
47/1649 (2.9) placebo 30/1655
(1.8) Incidence of cholelithiasis similar at
similar amounts of weight loss Postmarketing
reports pancreatitis
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PAC Meeting April 2007 Summary Orlistat

• Minimal use in pediatric patients
• Additional cases of cholelithiasis identified in
  adults
• Labeling reflects an increased risk of gallstone
  formation with substantial weight loss.
• FDA recommends routine monitoring of AEs for this
  drug in all populations.
• AE reporting for nonprescription products will be
  required in the near future.
• Does the Advisory Committee concur?

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Acknowledgements

• OSE
• Mark Avigan
• Vicky Borders- Hemphill
• Solomon Iyasu
• Rosemary Johann-Liang
• Joslyn Swann
• OPT
• Dianne Murphy
• Barbara Gould

• DMEDP
• Eric Colman
• Oluchi Elekwachi
• Theresa Kehoe
• Bruce Stadel
• DNCE
• Bindi Nikhar
• Joel Schiffenbauer
• Steven Osborne

• PMHS
• Lisa Mathis
• Jean Temeck
• Kristin Phucas