# Presentation: 864557

## One Year Post Exclusivity Adverse Event Review:Glimepiride  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**

## Background Drug Information 

**Drug: ** Amaryl® (glimepiride)
**Therapeutic Category:  **oral hypoglycemic agent
**Sponsor:  **Sanofi Aventis US
**Original Market Approval: **November 30, 1995
**Pediatric Exclusivity Granted:  **June 9, 2005
**Related combination products:   **
- AvandarylTM (glimepiride and rosiglitazone, approved 11/05)
- DuetactTM (glimepiride and pioglitazone, approved 7/06)
**Mechanism of action:**  stimulates insulin release from beta cells

## Background Drug Information

**Indication:**  adjunct to diet and exercise to lower blood glucose in patients with type 2 diabetes mellitus
- As monotherapy
- Concomitantly with metformin or insulin
**Dosage:**
- Adults only:  initial dose 1 to 2 mg daily with first main meal, maximum 8 mg maintenance

## Glimepiride:  Pediatric Exclusivity Labeling Changes

- Data are insufficient to recommend pediatric use
- Both pK and clinical trials for pediatric patients are described
- Single dose study (ages 10 to 17, n=30)
- 24 week clinical trial (n= 272, aged 8 to 17 years)
- Profile of adverse events similar to that in adults
- Comparative risk of hypoglycemia
- Hypoglycemia (BG < 36) observed in 4% of patients treated with glimepiride, 1% metformin

## Glimepiride:  Outpatient Use

- Total dispensed prescriptions for glimepiride and related antihyperglycemic agents (glipizide, glyburide, metformin and combinations of these) increased:
- Overall:  8% from 73.6 to 79.4 million1 (pre- and post-exclusivity; July 2004 to June 2005 vs. June 2005 to June 2006)
- glimepiride:  7% from 6.7 to 7.2 million (same time period)1
- Amaryl (glimepiride) 4th most commonly dispensed product1
- Pediatric use:  < 1%, decreased from 5,890 to 4,210 (pre and post-exclusivity)1
- 1Verispan LLC, Vector One® National (VONA), Jul 2003 – Jun 2006, Data extracted Sep 2006

## Glimepiride:  Adverse Events

- Pediatric AEs < 1 % of total
- Since Approval:  8/1494
- No pediatric deaths
- During post-exclusivity period:  2/290
- Two confounded, non-fatal, serious adverse events identified in pediatric patients during the post-exclusivity period:
- 17 year old with Trisomy 21 on amitryptiline who experienced behavioral abnormalities after 2 doses of glimepiride
- Infant with congenital anomalies (VSD, microcephaly, dysmorphic facies) after *in utero* exposure to mother with history of multiple miscarriages and 2 children with congenital anomalies; consanguinity
- Labeling:  Pregnancy category C; change to insulin.  Not recommended for use in pregnancy

## Summary:  Glimepiride

- As a result of exclusivity studies, labeling indicates there are insufficient data to recommend pediatric use
- No new pediatric AEs identified during one-year post-exclusivity period
- This completes the one-year post-exclusivity adverse event reporting as mandated by BPCA
- The FDA recommends routine monitoring of glimepiride for AEs in all populations
- Does the Advisory Committee concur?

## Acknowledgements

- _OSE_
- Laura Governale
- Lanh Green
- Joslyn Swann
- Rosemary Johann-Liang
- _PMHS_
- Lisa Mathis
- Kristin Phucas
- Jean Temeck

- _DPEP_
- Robert Misbin
- David Orloff
- _OPT_
- Dianne Murphy
- Ann Myers