Carbamazepine Toxicity

Is Testing Right for Me? I Have My Test Results

Carbamazepine Toxicity

What Are Carbamazepine, Phenytoin, and Fosphenytoin?

Carbamazepine, phenytoin, and fosphenytoin are drugs commonly used to treat:

  • Epiliepsy, including grand mal seizures and psychomotor seizures
  • Pain in the nerves of the face caused by trigeminal neuralgia
  • Bipolar disorder

Generic Name
Brand Name
carbamazepine Tegretol, Equetro, Carbatrol, Atretol, Epitol, Teril
phenytoin Dilantin, Phenytek, Diphenylan
fosphenytoin Cerebyx

Side Effects

Like all drugs, carbamazepine, phenytoin and fosphenytoin can cause side effects.  Many of these are mild and temporary, like drowsiness and vomiting. However, severe side effects can develop that need immediate medical attention. Sometimes these drugs can damage the bone marrow, which increases the chance of getting sick. Problems with the liver and kidneys are also possible.

The most severe side effects are skin reactions. These skin reactions usually show up within a few weeks of starting drug treatment. The most common serious skin reactions are:

Stevens-Johnson syndrome (SJS): The symptoms of SJS begin with fever and tiredness, followed by a rash, severe skin wounds, and shedding of the skin. Up to 10% of the skin can be affected. Wounds may also appear in other tissues that cover the eyes, mouth, and genitals. Up to 5% of SJS cases are fatal.
Toxic Epidermal Necrolysis (TEN): This syndrome is more severe than SJS, and can be life threatening. It also begins with fever and tiredness followed by a rash and skin wounds that may resemble extensive burns. However, 30% or more of the skin may be affected. Between 25% and 35% of TEN cases are fatal.

Inherited gene changes may help explain these serious skin reactions in certain people.

Next: What Contributes to Serious Skin Reactions?

Why are you considering HLA-B*1502 testing?

I have Asian ancestry and I am considering starting carbamazepine, phenytoin, or fosphenytoin to treat a health problem.

I have Asian ancestry and I am currently taking carbamazepine, phenytoin, or fosphenytoin.

None of these

HLA-B*1502 testing may be useful for you. Asian people from regions with a high chance of the HLA-B*1502 variation should have testing to find those at highest risk for severe skin reactions.

Population HLA-B*1502 Frequency
Asian (overall) 5.1%
Singapore 11.6%
Han Chinese 10.2%
Malay 8.4%
Taiwanese 8%
Thai 6.1%
Filipino 5.3%
Indian-Khandesh Pawra 6%
Indian-Northern Hindi 2%
Indian-Mumbai Marathas 1%
Japanese <1%
Korean 0.5%
African 0.2%
European Caucasian Up to 0.1%%
Hispanic 0%
Native American 0%

If you have testing before you start carbamazepine, phenytoin or fosphenytoin therapy, it may help you avoid serious side effects of the drug. Genetic test results don't change over time. So, you only have to have HLA-B*1502 testing once in your lifetime.

Possible Test Results and How They May Change Your Care

  • A negative result for HLA-B*1502 means that you don't have this variant. Your doctor can begin your carbamazepine, phenytoin or fosphenytoin therapy with less concern that you will develop Stevens Johnson Syndrome (SJS) or toxic epidermal necrolysis (TEN). You will still need to be monitored for side effects from these drugs. Normal results don't rule out the chance of side effects.
  • A positive result for HLA-B*1502 means that you do have this variant. Carbamazepine, phenytoin, or fosphenytoin therapy should be avoided because of the risk of SJS and TEN. Other drugs that do similar things but don't have the same risk of skin reactions can be used. On the other hand, your doctor may decide that the benefits of carbamazepine, phenytoin, or fosphenytoin outweigh the risk of side effects. In this case, you will need to be watched carefully for any skin symptoms.

HLA-B*1502 testing may not be useful for you. This test is most useful for finding Asian people who have a higher-than-average risk for the serious skin reactions – Stevens Johnson Syndrome (SJS) or toxic epidermal necrolysis (TEN) – while taking carbamazepine. Phenytoin and fosphenytoin may also increase this risk in people with the HLA-B*1502 variation.

Most people will have signs of SJS or TEN within the first few months of treatment, if they are going to have these reactions. If you have been taking one of these drugs for more than a few months without developing SJS or TEN, you are at a low risk for these adverse skin effects. Testing at this point is probably not that helpful for you. On the other hand, if you just recently started therapy, your doctor may decide that testing is worthwhile.

You should continue to be monitored for side effects like everyone else who takes carbamazepine, phenytoin, and fosphenytoin. The most common serious side effects from these drugs are a low blood count, and problems with the liver or kidneys. Your doctor can check for these with routine lab testing.

If you developed SJS or TEN while taking one of these drugs in the past, HLA-B*1502 testing could help explain why you had this reaction. However, you probably need to avoid these and other similar drugs simply based on your past reaction, so these results may not change your medical care.

HLA-B*1502 testing may not be useful for you. The main reasons for testing are reviewed in the Who Should Consider Testing section. Testing is not recommended for people who don't have Asian ancestry. Testing is currently only useful when starting (or possibly very early in) carbamazepine, phenytoin, or fosphenytoin therapy.

If you have a reason for testing that isn't covered here, talk to your doctor or a genetic counselor about whether testing might be useful for you.