Presentation: Patient of Asian ethnicity requiring carbamazepine

A 25-year-old man of Han Chinese origin requires carbamazepine for the treatment of epilepsy. The risk of carbamazepine-induced severe cutaneous reaction may be increased due to his ethnic origin.

• HLA-B*15:02 and HLA-A*31:01 have distinct ethnic and geographical distributions that are important for evaluating population risk. While severe cutaneous reactions are estimated to occur in between 1 and 6 per 10,000 new users of carbamazepine in countries with mainly White populations, the risk in some Asian populations is thought to be up to 10 times higher. Associations between HLA-B*15:02 and HLA-A*31:01 and carbamazepine hypersensitivity have been recorded in children as well as in adults. Strong association with drug-induced liver injury has also been reported.
• The summary of product characteristics for carbamazepine (sold under the brand name Tegretol) indicates that patients of Han Chinese and Thai origin should, whenever possible, be screened for HLA-B*15:02 before starting treatment, but that there is insufficient data to support a recommendation for HLA-A*31:01 screening. Prior screening for HLA-B*15:02 in patients of Han Chinese, Hong Kong Chinese and Thai origin was also recommended by the Medicine and Healthcare products Regulatory Agency in 2008.

• At the time of writing, the National Genomic Test Directory does not include pharmacogenomic testing for HLA-B*15:02 or HLA-A*31:01 variants, although tests may be available via your regional Genomic Laboratory Hub or other local laboratories (such as histocompatibility or immunogenetics laboratories).
• • For information about how to arrange testing in Wales, Scotland or Northern Ireland, see Genomic testing in the devolved nations.
• For human leukocyte antigen (HLA) testing (and other DNA-based tests), an EDTA sample (typically in a purple-topped tube) is required.
• For more information on genomic testing for the HLA-B*15:02 and HLA-A*31:01 variants, including how identification of these alleles affects patient management, see Patient requiring carbamazepine with a known variant in the HLA-B*15:02 or HLA-A*31:01 allele.
• If you are discussing genomics concepts with your patients, you may find it helpful to use the visual communication aids for genomics conversations.
• Information about patient eligibility and test indications were correct at the time of writing. When requesting a test, please refer to the National Genomic Test Directory to confirm the right test for your patient.

For clinicians

• Clinical Pharmacogenetics Implementation Consortium (CPIC): Guideline for HLA genotype and use of carbamazepine and oxcarbazepine: 2017 update (PDF, eight pages)
• Electronic Medicines Compendium (EMC): Tegretol 100mg tablets summary of product characteristics
• Medicines and Healthcare products Regulatory Agency: Drug safety update: Carbamazepine, oxcarbazepine and eslicarbazepine: Potential risk of serious skin reactions
• NHS England: National Genomic Test Directory
• OMIM: 608579 Severe cutaneous adverse reaction, susceptibility to

References:

• Amstutz U, Ross CJD, Castro-Pastrana LI and others. ‘HLA-A*31:01 and HLA-B*15:02 as genetic markers for carbamazepine hypersensitivity in children‘. Clinical Pharmacology & Therapeutics 2013: volume 94, issue 1, pages 142–149. DOI: 10.1038/clpt.2013.55
• Khoo ABS, Ali FR, Yiu ZZN and others. ‘Carbamazepine induced Stevens-Johnson syndrome‘. British Medical Journal Case Reports 2016. DOI: 10.1136/bcr-2016-214926
• Manson LEN, Swen JJ and Guchelaar HJ. ‘Diagnostic test criteria for HLA genotyping to prevent drug hypersensitivity reactions: A systematic review of actionable HLA recommendations in CPIC and DPWG guidelines‘. Frontiers in Pharmacology 2020: volume 11, article number 567048. DOI: 10.3389/fphar.2020.567048
• Nicoletti P, Barrett S, McEvoy L and others. ‘Shared genetic risk factors across carbamazepine-induced hypersensitivity reactions‘. Clinical Pharmacology & Therapeutics 2019: volume 106, issue 5, pages 1,028–1,036. DOI: 10.1002/cpt.1493.

For patients

• Medicines for Children: Oral carbamazepine for preventing seizures (PDF, two pages)