A pharmacogenomics consultation is requested for a 35-year-old woman with bipolar disorder about to start lamotrigine. Her HLA genotype is HLA-B*15:02. What is the clinical significance of this finding?

• A HLA-B*15:02 confers near zero risk of lamotrigine-induced Stevens-Johnson syndrome in all populations
• B HLA-B*15:02 is strongly associated with carbamazepine- and phenytoin-induced severe cutaneous adverse reactions but evidence for lamotrigine association is primarily for Asian populations and should prompt caution ✓
• C HLA-B*15:02 carriers should receive double the standard lamotrigine dose for efficacy
• D HLA-B*15:02 predicts poor lamotrigine metabolism through CYP2C19, leading to drug accumulation

Explanation

HLA-B*15:02 is found predominantly in South and Southeast Asian populations and is strongly associated with carbamazepine-induced Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) — the FDA recommends testing before carbamazepine use in these populations. For lamotrigine, HLA-B*15:02 also shows association with SJS/TEN specifically in Asian (particularly Han Chinese and Thai) populations, though the association is weaker than with carbamazepine. Lamotrigine's main SJS risk factors are rapid dose escalation and concomitant valproate (which inhibits UGT1A4 glucuronidation of lamotrigine). A different allele, HLA-A*31:01, is relevant for carbamazepine hypersensitivity in Caucasians.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

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Written and medically reviewed by the StethoPrep medical team.