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Health Sciences Authority
Safety Alerts

HLA-B*1502 genotype testing: Towards safer use of carbamazepine

Audiences

Healthcare professional

Industry member

Product type

Therapeutic Products

31 December 2013

This article has been migrated from an earlier version of the site and may display formatting inconsistencies.

On 30 April 2013, a Dear Healthcare Professional Letter (DHCPL) was jointly issued by the Ministry of Health (MOH) and HSA to highly recommend genotyping for HLA-B*1502 allele prior to initiation of carbamazepine (CBZ) therapy in new patients of Asian ancestry, as genotyping for this group of patients is now considered the standard of care.1 This recommendation was based on both local and international data supporting a strong association between HLA-B*1502 and CBZ-induced Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN).

A HSA-initiated multi-centre study at Changi General Hospital, Singapore General Hospital and National University Hospital (NUH) found a strong association between the HLA-B*1502 allele and CBZ-induced SJS/TEN (Odds ratio 181, p<0.0001). The results were consistent with international data that HLA-B*1502 carriers have an elevated risk of developing SJS/TEN when taking CBZ.

As of 1 November 2013, a total of 307 blood samples were sent to the NUH Molecular Diagnostic Centre for HLA-B*1502 genotype testing, and 30 (9.8%) of these samples tested positive for the presence of the HLA-B*1502 allele. Over the past 10 years, HSA received an average of 15 reports of CBZ-induced SJS/TEN per year. After the implementation of HLA-B*1502 genotype screening, HSA has not received any reports of SJS/TEN associated with the use of CBZ in patients screened for the HLA-B*1502 allele.

Healthcare professionals are reminded to take note of the following:

  • CBZ is indicated for the treatment of epilepsy and other conditions such as bipolar disorders, alcohol-withdrawal syndrome, trigeminal neuralgia, diabetic neuropathy and diabetes insipidus centralis. Testing for the presence of HLA-B*1502 allele is highly recommended in new patients of Asian ancestry, regardless of the indication for which the drug is used.

  • CBZ should not be prescribed prior to the return of HLA-B*1502 test results. This is because of the possibility of development and progression of SJS/TEN in susceptible patients even after prompt discontinuation of the drug.

  • The use of CBZ should be avoided and treatment alternatives are recommended in patients who are found to be positive for HLA-B*1502. Preliminary data have shown a suspected association between this allele and phenytoin-induced SJS/TEN, although the effect size is not as large.2,3 As a precaution, patients who are identified to be positive for the HLA-B*1502 allele should also not be prescribed phenytoin.

  • Genetic testing should not substitute for appropriate clinical vigilance and patient management. Although rare, patients negative for HLA-B*1502 could still develop SJS/TEN as the role of other factors such as drug dose, concomitant medications and co-morbidities have not been studied.

Healthcare professionals are also encouraged to report any adverse reactions suspected to be associated with the use of CBZ to the Vigilance Branch of HSA.

References

  1. MOH/HSA Dear Healthcare Professional Letter: Recommendations for HLA-B*1502 genotype testing prior to initiation of carbamazepine in new patients. 30 Apr 2013, No. 49. 

  2. Epilepsia 2008; 49: 2087-91

  3. Pharmacogenomics 2010; 11: 349-56

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