# Presentation: 883675

## One Year Post Exclusivity Adverse Event Review Update:Orlistat  Pediatric Advisory Committee Meeting April 11, 2007

**Hari Cheryl Sachs, MD, FAAP****Medical Officer**
**Pediatric and Maternal Health Staff**
**Office of New Drugs **
**Food and Drug Administration**

## 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.

## 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

## Background Drug Information

**Orlistat Rx (Xenical)**
**Indication (**_**>**_** 12 years of age): **
- Obesity management in conjunction with weight loss
- Body Mass Index (BMI) > 30 mg/m2 or 27 mg/m2 with risk factors (hypertension, diabetes, dyslipidemia)
- Dosage:  120 mg TID
**Orlistat OTC (Alli)**
**Indication:  (**_**>**_** 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

## 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 <1 % of prescriptions annually.2
**	****1**Verispan, LLC, Vector One® National (VONA) Data extracted 1-12-2007
**	****2**Verispan, Total Patient Tracker, data extracted 1-18-2007

## 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

## 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

## 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?

## 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