Reminder to verify HLA-B*1502 status in new patients of asian ancestry before starting carbamazepine treatment

HSA would like to remind healthcare professionals to verify the HLA-B*1502 status before starting carbamazepine (CBZ) treatment in new patients of Asian ancestry. Patients who are HLA-B*1502-positive are at an increased risk of developing severe cutaneous adverse reactions (SCARs), particularly Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis (SJS/TEN) during treatment with CBZ.

CBZ is an anticonvulsant indicated for the treatment of epilepsy and other conditions such as diabetic neuropathy, trigeminal neuralgia and bipolar disorders. It has been registered in Singapore since 1988 and is currently available as Tegretol® (Novartis) and two other generic products.

 

About HLA-B*1502 genotype testing

Genotyping for HLA-B*1502 prior to treatment initiation with CBZ in new patients of Asian ancestry has been the standard of care in Singapore since 2013.1 This one-time test helps distinguish high-risk patients who should avoid CBZ from low-risk patients who are able to continue to use this low-cost yet effective medicine. The implementation of this recommendation has contributed to a 92% reduction in the number of CBZ-associated SJS/TEN cases in Singapore, from 50 cases in the 5-year pre-implementation period (2008 - 2013) to 4 cases in the post-implementation period (2013-2018).2

The HLA-B*1502 genotyping test is available at the National University Hospital Molecular Diagnosis Centre, the Tan Tock Seng Hospital Molecular Diagnostic Laboratory, the DNA Diagnostic & Research Laboratory at Kandang Kerbau Women's and Children's Hospital, and the Tissue Typing Laboratory at the Health Sciences Authority of Singapore. The estimated turnaround time for the test result is one to four working days. Subsidised patients from the MOH-funded restructured hospitals and institutions would qualify for a flat rate subsidy of 75% of the cost of the test.

 

HSA’s advisory

Healthcare professionals are advised to take note of the following:

  • HLA-B*1502 genotype testing specifically identifies patients at risk of developing CBZ-induced SJS/TEN, but not CBZ-induced drug rash with eosinophilia and systemic symptoms (DRESS)
  • HLA-B*1502 test results should be obtained prior to prescribing CBZ as SJS/TEN can develop and progress in susceptible patients, even after prompt discontinuation of the drug
  • The use of CBZ should be avoided and treatment alternatives are strongly recommended in patients who are found to be positive for HLA-B*1502. As a precaution, these patients should also not be prescribed phenytoin, as there is preliminary data suggesting a suspected association between HLA-B*1502 and phenytoin-induced SJS/TEN
  • Although reported to be rare, patients who test negative for HLA-B*1502 may still be at risk of developing CBZ-induced SJS/TEN. The role of other factors, which may contribute to the development of SJS/TEN in these patients, such as drug dose, concomitant medications and co-morbidities, have not been studied
  • Clinical vigilance for CBZ-induced SCARs including DRESS should continue, especially during the first 12 weeks following treatment initiation with CBZ

Healthcare professionals are encouraged to report any suspected serious adverse reactions related to CBZ use to the Vigilance and Compliance Branch.

 

References

  1. https://www.hsa.gov.sg/announcements/safety-alert/recommendations-for-hla-b-1502-genotype-testing-prior-to-initiation-of-carbamazepine-in-new-patients
  2. https://www.frontiersin.org/articles/10.3389/fphar.2020.00527/full
Healthcare professional, Industry member, Therapeutic Products
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