Carbamazepine and HLA-B*15:02

Jeanette Taylor, Pharm.D. Candidate; Sarah Kradel, Pharm.D. Candidate; Christina Ciccone, Pharm.D. Candidate; Victoria Ridge, Pharm.D. Candidate; Matthew Irwin, Pharm.D. Candidate.

About the Drug

Carbamazepine (Tegretol® and generic products) is given to patients with epilepsy as an anticonvulsant drug. Epilepsy is a disorder that affects the brain, causing a person to have seizures (several repeating, unpredictable convulsions) over time. It is also used as a painkiller to treat patients who suffer from a type of facial nerve pain known as trigeminal neuralgia.

About the Gene

The gene of interest for this medication is known as HLA-B. HLA-B is called a class I gene that provides instructions for making proteins critical in the immune system. These specific proteins allow the immune system to distinguish the body’s own proteins from proteins made by invading foreign cells (like bacteria).

About the Drug-Gene Interaction

The specific form of HLA-B of interest in patients taking carbamazepine is known as HLA-B*15:02, which can cause two severe skin disorders: Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN). One to six out of 10,000 new Caucasian users will experience severe reactions. The risk in patients of Asian descent, Chinese ancestry in particular, is estimated to be about 10 times higher. Studies have found that in patients of Chinese descent there is a strong association between the risk of developing a severe skin reaction and the presence of the HLA-B*15:02 form of the gene. It should be noted that the presence of HLAB*15:02 increases the risk of SJS and TEN in all individuals, regardless of ethnicity.

Patients taking carbamazepine should contact a healthcare professional and will likely be told to discontinue use of the medication if a rash or skin reaction develops, unless it is clear the rash is not related to the drug. If the rash/skin reaction is related to the drug, an alternative treatment should be used.

There is a genetic test that can be used to identify which patients are HLA-B*15:02 positive. It is important to discuss this with your doctor and pharmacist.

Drug-Gene Interaction Example

Jim, an Asian male, starts taking carbamazepine for the first time. Jim's doctor has diagnosed him with epilepsy and believes the medication will help control his seizures. Prior to prescribing carbamazepine, Jim’s doctor recommended a genetic test of his HLA-B genotype. The doctor explained that this test will help select an optimal dose of carbamazepine, lowering Jim’s risk of an adverse medication effect called Stevens-Johnson syndrome. Jim declined because he did not want to spend the extra time and money to perform the test. Six weeks after starting carbamazepine, Jim notices a strange rash on his chest that seems to be getting worse every day. Concerned, he decides to go to the emergency room, where he is diagnosed with Stevens-Johnson syndrome and admitted for immediate treatment. Eventually he is released from the hospital, and must recuperate at home for two weeks. Jim’s doctor prescribes him a different medication to control his seizures.

Although Jim had to make an expensive trip to the hospital and recuperate at home for two weeks from his skin reaction, this was only a mild case of Stevens-Johnson syndrome. More severe cases may result in permanent disfigurement and even death.

HLA-B testing does not completely rule out the risks of taking carbamazepine, nor does it guarantee the medication will work for you. Genetic testing is a guide to personalize the treatment of patients, maximizing benefit and minimizing harm.

Provider Information

The links below provide access to important articles and information relative to carbamazepine. The links are to external websites and will be checked regularly for consistency.

Sources of Information

DailyMed [Internet]. Bethesda (MD): U.S. National Library of Medicine; c1993-2012. Carbamazepine; [cited 2012 Oct 19]; [about 4 screens]. Available from: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c13bc0b8-7900- 4ef4-98ed- e1315a08d95d/.

Ferrell PB Jr, McLeod HL. Carbamazepine, HLA-B*1502 and risk of Stevens-Johnson syndrome and toxic epidermal necrolysis: US FDA recommendations. Pharmacogenomics. 2008 Oct;9(10):1543-6.

Mockenhaupt M. Risk of Stevens–Johnson syndrome and toxic epidermal necrolysis in new users of antiepileptics. Neurology. 2005;64:1134-38.

National Center for Biotechnology Information [Internet]. Bethesda (MD): National Center for Biotechnology Information; 2012. HLA-B major histocompatibility complex, class I, B [ Homo sapiens (human) ]; [cited 2012 Oct 9]; [about 17 screens]. Available from: https://www.ncbi.nlm.nih.gov/gene/3106/.

PharmGKB [Internet]. Stanford (CA): U.S. Department of Health and Human Services; c2001-2017. Carbamazepine; [cited 2012 Oct 19]; [about 2 screens]. Available from: https://www.pharmgkb.org/chemical/PA448785?previousQuery=Carbamazepene/.