Results: Patient requiring carbamazepine with a known variant in the HLA-B*15:02 or HLA-A*31:01 allele

A 25-year-old man requires carbamazepine for the treatment of epilepsy. He has been tested previously and was found to have the HLA-B*15:02 allele.

• Variants in the HLA-B*15:02 and HLA-A*31:01 alleles are associated with an increased risk of severe cutaneous and hepatic adverse reactions (such as Stevens-Johnson syndrome) in patients treated with carbamazepine.
• 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.

• Pharmacogenomic test results should be used as follows.
  • Carbamazepine-naive patients who test positive for HLA-B*15:02: do not prescribe carbamazepine.
  • Patients who have received carbamazepine consistently for longer than three months and test positive for HLA-B*15:02: cautiously consider prescribing carbamazepine.
  • Carbamazepine-naive patients who test positive for HLA-A*31:01: do not prescribe carbamazepine unless no alternative treatment options exist.
    • If no alternative treatment options exist, consider the use of carbamazepine with increased frequency of clinical monitoring and discontinue carbamazepine at the first sign of a cutaneous adverse reaction.
  • Patients who have received carbamazepine consistently for longer than three months and test positive for HLA-A*31:01: cautiously consider prescribing carbamazepine.
• It should be noted that not all carbamazepine-induced cutaneous or hepatic adverse reactions can be attributed to HLA-B*15:02 or HLA-A*31:01. All patients should be monitored as standard practice.
• For more information about genomic testing for HLA-B*15:02 and HLA-A*31:01 variants, including how identification of variants affects patient management, see our Knowledge Hub resource, Carbamazepine.
• For information about how to arrange testing in Wales, Scotland or Northern Ireland, see our dedicated Knowledge Hub resource.

For clinicians

• Clinical Pharmacogenetics Implementation Consortium: CPIC® Guideline for HLA genotype and Use of Carbamazepine and Oxcarbazepine
• 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

References:

• Amstutz U, Ross CJ, 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: volume 2016, article number bcr2016218359. DOI: 10.1136/bcr-2016-214926
• 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 1028–1036. DOI: 10.1002/cpt.1493

For patients

• Medicines for Children: Carbamazepine (oral) for preventing seizures