HLA genotype testing for Carbamazepine, Oxcarbazepine, and Eslicarbazepine: a guideline developed by the UK Centre of Excellence in Regulatory Science and Innovation in Pharmacogenomics (CERSI-PGx)

Carbamazepine is licensed in the United Kingdom for the treatment of epilepsy, bipolar disorder and trigeminal neuralgia. The related compounds oxcarbazepine and eslicarbazepine are licensed for the treatment of epilepsy. These drugs can cause immune‐mediated hypersensitivity reactions, which typically affect the skin, and can be of variable severity. The liver and other organ systems can also be affected. The HLA alleles, HLA‐B*15:02, HLA‐B*15:11 and HLA‐A*31:01, are known predisposing factors for these hypersensitivity reactions. Any treatment‐naïve patient, regardless of ancestry or indication for treatment, who is about to be prescribed carbamazepine, oxcarbazepine or eslicarbazepine, or has been on these drugs for less than 3 months, should undergo pharmacogenetic testing to identify all clinically relevant HLA alleles to reduce the risk of hypersensitivity reactions. Carbamazepine, oxcarbazepine and eslicarbazepine should be avoided in HLA‐B*15:02‐positive patients. These drugs should also be avoided in patients positive for HLA‐A*31:01 or HLA‐B*15:11 if an alternative is possible. Where it is not possible to use an alternative, treatment should only be commenced after careful consideration of the benefits and risks, with increased monitoring and advising patients on appropriate action to take if a skin rash occurs. Our guideline is compatible with other international pharmacogenetics prescribing guidelines. This guideline is grounded in the latest evidence but cannot account for all individual factors relevant to patient care. Therefore, prescribers must conduct a thorough assessment of each patient's risk–benefit profile, ensuring that therapy is optimised to maximise benefits whilst minimising potential harms.