Lamotrigine (Lamictal)
A common medicine for epilepsy and bipolar disorder that, rarely, causes a dangerous rash. Its US label now names one gene, HLA-B*15:02, as one of four things that make that rash more likely.
What this drug connects to
The genes involved
Lamotrigine, used for epilepsy and bipolar disorder, can cause this reaction too, usually in the first 2 to 8 weeks. Its US label lists four things that make a serious rash more likely: taking it with valproate, starting above the recommended dose, raising the dose faster than recommended, and carrying HLA-B*15:02, the same immune gene version that matters for carbamazepine. In studies of patients of Asian ancestry, such as Han Chinese and Thai patients, carriers had about 2 to 3 times the risk. The label does not require a test: for someone known to carry it, it asks the prescriber to weigh the risks and benefits, and it says a test must never replace watching for a rash.
US prescribing information for LAMICTAL (lamotrigine), revised October 2025: Boxed Warning and section 5.1, Serious Skin Rashes. This is the label itself, not a CPIC guideline.
Questions about Lamotrigine (Lamictal)
What is lamotrigine?
Lamotrigine (brand name Lamictal) is a medicine for epilepsy and for keeping mood steady in bipolar disorder. Most people take it without trouble. Its best-known danger is a rare but serious skin rash, which is why it is started at a low dose and raised slowly.
What does the HLA-B*15:02 gene have to do with lamotrigine?
HLA-B is one of the genes your immune system uses to tell your own cells from invaders. One version of it, HLA-B*15:02, can make the immune system react to certain medicines as if they were a threat. In studies of patients of Asian ancestry, such as Han Chinese and Thai patients, people carrying it had a risk of Stevens-Johnson syndrome about 2 to 3 times higher on lamotrigine.
What are the four things that raise the rash risk?
The label lists four: taking lamotrigine together with valproate, starting at a higher dose than recommended, raising the dose faster than recommended, and carrying HLA-B*15:02. Three of the four are about how the medicine is taken, which is why the slow start matters so much. The label also says serious rashes have happened in people with none of the four.
How often does the serious rash happen?
According to the label, a rash serious enough to need a hospital stay and stopping the medicine happens in about 0.3% to 0.8% of children aged 2 to 17, and about 0.08% to 0.3% of adults. Nearly all the life-threatening cases started within 2 to 8 weeks of beginning treatment.
Do I need a gene test before taking lamotrigine?
The label does not require one. If someone is already known to carry HLA-B*15:02, it asks the prescriber to weigh the risks and benefits. It also warns that a test has real limits: many carriers never react, people without it can still react, and a test must never replace watching for a rash. Any new rash on lamotrigine is a reason to contact your doctor straight away: the label says the medicine should usually be stopped at the first sign of a rash, unless the rash is clearly not caused by it.
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Lamotrigine (Lamictal). MyGeneLog™. https://www.mygenelog.com/drugs/lamotrigine