Serious skin reactions from Carbamazepine : reports from Thaivigibase

1
Serious skin reactions from Carbamazepine
reports from Thaivigibase

• Health Product Vigilance Center (HPVC)
• Food and Drug Administration, Ministry of
  Public Health, Thailand

2
Introduction

• The most serious skin reactions reported from
  prescribing some group of drugs are
  Stevens-Johnson syndrome (SJS) and toxic
  epidermal necrolysis (TEN).
• These reactions can lead patients severely ill
  and finally dead.

3
Introduction

• On December 2007, US. Food and Drug
  Administration (FDA) issued an alert for
  healthcare professionals concerning the dangerous
  or even fatal skin reactions (Stevens Johnson
  syndrome and toxic epidermal necrolysis), that
  can be caused by carbamazepine therapy.

4
Introduction

• The latest information about the genetic
  association of some drugs- serious reactions has
  been clarified.
• The HLA- B1502 allele (which caused SJS) is
  significantly more common in patients exclusively
  in patients with ancestry across broad areas of
  Asia, including South Asian Indians and Thais.

5
Introduction

• Descriptive analysis of adverse reactions from
  carbamazepine use in Thaivigibase would be
  compared those reactions to the new information
  in Thai patients.
• Proper recommendation and regulatory action would
  be performed from this experience.

6
Review of Carbamazepine

• Carbamazepine is labeled for use in the following
  indication Bipolar I disorder, acute manic and
  mixed episodes, Epilepsy, Partial, generalized,
  and mixed types , Glossopharyngeal neuralgia and
  Trigeminal neuralgia.

7
Side effects and toxicity

• Carbamazepine can produce dose-related adverse
  effects, which include dizziness, diplopia,
  nausea, ataxia, and blurred vision. Rare
  idiosyncratic adverse effects include aplastic
  anemia, agranulocytosis, thrombocytopenia,
  Stevens-Johnson syndrome and asymptomatic
  elevation of liver enzymes.

8
Objectives

• To describe and characterize skin and appendage
  adverse drug reaction reported in patients
  receiving carbamazepine in Thailand from
  Thaivigibase.
• 5 years experience

9
Methodology

• During 2003 to 2007, we carried out a
  retrospective search in the Thaivigibase of
  spontaneous adverse drug reaction database.
• Reports were included if they had been recorded
  at least one prescription of carbamazepine from
  the hospitals and clinics between January 1, 2003
  to December 31, 2007.

10
Methodology

• A search of preferred term for potential cases
  were all reports of skin and appendage disorders.
• Information on patient demographic information ,
  medical history, clinical conditions and
  concomitant drug and sources of reports were
  collected.

11
Methodology

• Reports were excluded if they had no record of
  carbamazepine for suspected or concomitant drug
  during the study period.
• Descriptive statistics was calculated. The
  analysis was performed with chart and cumulative
  percentage.

12
Results

• A total of 1,132 reports with 1,769 adverse
  reactions were reported during study period.
• Most reports came from general hospitals
  (25.49), center hospitals (25.04) and community
  hospitals (19.80).

13
The percentage of reports categorized by source
of report
14
Results

• The age range of reported cases was 3 months to
  89 years (median, 44 years).
• 693 reports of 1,132 reports (61.21.) were male.
  
• 19 of 154 reports (12.33) with allergic history
  information had carbamazepine associated reaction
  experience.

15
Results

• 648 reports (57.24) were serious adverse drug
  reactions. Almost of them (83.48) resulted in
  admitted or prolonged hospitalization.
• Two fatal outcome cases were reported due to
  Stevens-Johnson syndrome (SJS) and Toxic
  epidermal necrolysis (TEN).

16
Results

• 1,230 of 1,769 events (69.53) were described as
  skin reaction
• Stevens Johnson syndrome (SJS) was the most
  frequently reported event (32.85)
• followed by maculo-pupular rash ((13.50) and
  rash (11.95).

17
Results

• Other severe skin reaction including
• 1.10.55 of erythema multiforme (EM)
• 2.3.09 of toxic epidermal necrolysis (TEN)

18
The percentage of skin reactions
19
Conclusions

• Stevens Johnson Syndrome (SJS) was the highest
  reported adverse drug reactions.
• Our findings are consistent with available
  evidence with the literature reported.

20
Recommendations

• Further analytical study and pharmacogenomic
  study should be conducted.
• HPVC center will collaborate with the genetic
  section to study the association and further
  reducing these severe skin reactions

21
Recommendations

• The cost-effectiveness study on gene testing
  before prescribing carbamazemine is ongoing
  performed.

22
Acknowledgements

• Networking centers contributing data to the
  Health Product Vigilance Center.
• All staffs at Health Product Vigilance Center,
  FDA, Thailand.

23
Thank you for your attention