Psychopharmacologic Drugs Advisory Committee June 16, 2003

1
Psychopharmacologic Drugs Advisory
CommitteeJune 16, 2003

• Tarek A. Hammad, MD, PhD, MSc, MS
• Medical Reviewer
• Division of Neuropharmacological Drug Products
• Center for Drug Evaluation and Research, FDA

1
2
Outline

• Generic Drugs Registry Data
• Are We Seeing the Full Picture?
• Agranulocytosis Rates Stratified by Monitoring
  Frequency after 6 Months in the US and 1 Year in
  the UK

2
3
Generic Drugs Registry Data

• Generic clozapine became available in 1997
• Data from two manufacturers- Ivax and Mylan
• Only first time users of clozapine were included
• First time users accounted for only about 10-20
  of all users in the generic databases
• Small number of patient-years
• 1007 py before 2937 py after 6 ms, across the
  two databases
• Demographics are reasonably similar to the
  innovator data in the US CNR

3
4
Generic Drugs Registry Data (first 6 months of
therapy)
4
5
Generic Drugs Registry Data (After 6 months of
therapy)
5
6
Outline

• Generic Drugs Registry Data
• Are We Seeing the Full Picture?
• Agranulocytosis Rates Stratified by Monitoring
  Frequency after 6 Months in the US and 1 Year in
  the UK

6
7
US Rates After First 6 Months (weekly monitoring
in old system and every two weeks in new system)
US Rates During First 6 months (weekly
monitoring under both systems)
7
8
Detection of Moderate Leukopenia

• UK system uses WBC and ANC
• Two parallel tests increase sensitivity
• Help detect more potentially vulnerable patients
• Premise Pts with low ANC preceding low WBC are
  detected later in a system that follows only WBC
• Might explain apparent higher rates in UK

8
9
Agran Rates by Monitoring Period US Vs. UK
9
10
Mortality Rate Due to Agran by Monitoring Period
US Vs. UK
10
11
Outline

• Generic Drugs Registry Data
• Are We Seeing the Full Picture?
• Agranulocytosis Rates Stratified by Monitoring
  Frequency after 6 Months in the US and 1 Year in
  the UK

11
12
Moderate Leukopenia and Agran Rates in the US in
the current system after 6 months
13
Moderate Leukopenia and Agran Rates in the UK in
the current system after 1 year
14
Progression from moderate leukopenia to agran in
the UK across monitoring frequencies after 1 year
15
(No Transcript)
16
Progression from moderate leukopenia to agran in
the US across monitoring frequencies after 6
months
17
The number of new users of clozapine for the four
months prior to the repeated suicidality
indication approval in December 2002 and the
subsequent months to April 2003
17