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SEE ANNOUNCEMENT BELOW!
Steps to Implementing Pharmacogenomics (PGx) in Your Practice
Carbamazepine, SJS, TEN, and HLA-B*15:02
Borrowing a case from a very good and recommended book on PGx1, we have WH, a 17 yo African American/Asian male with a history of head trauma resulting from an automobile accident occurring four months earlier. After experiencing some episodes of unprovoked aggressiveness and agitation, his mother states to the neurologist that the episodes have been increasing recently. WH is diagnosed with acquired brain injury following examination of a CT scan.
The neurologist decides to start WH on carbamazepine for the treatment of agitation and aggression caused by closed head trauma. Since there is a strong association between carbamazepine use and Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in individuals with this allele, genetic testing is performed for the HLA-B*15:02 allele.
The Asian population is at higher risk regarding the potential for TEN and SJS with the administration of carbamazepine. Genotyping of individuals of Asian ethnicity would be prudent when considering the risk/benefit ratio of the use of carbamazepine. The HLA-B*15:02 Allele Frequencies in Major North American Populations1 is as follows:
| Ethnicity | Allele Frequency (%) | n |
|---|
| Asian | 5.1 | 396 |
| African | 0.2 | 251 |
| European | 0 | 287 |
| Hispanic | 0 | 240 |
PACKAGE INSERT-BOX WARNING FOR CARBAMAZEPINE
WARNINGS SERIOUS DERMATOLOGIC REACTIONS AND HLA-B*1502 ALLELE SERIOUS AND SOMETIMES FATAL DERMATOLOGIC REACTIONS, INCLUDING TOXIC EPIDERMAL NECROLYSIS (TEN) AND STEVENS-JOHNSON SYNDROME (SJS), HAVE BEEN REPORTED DURING TREATMENT WITH TEGRETOL. THESE REACTIONS ARE ESTIMATED TO OCCUR IN 1 TO 6 PER 10,000 NEW USERS IN COUNTRIES WITH MAINLY CAUCASIAN POPULATIONS, BUT THE RISK IN SOME ASIAN COUNTRIES IS ESTIMATED TO BE ABOUT 10 TIMES HIGHER. STUDIES IN PATIENTS OF CHINESE ANCESTRY HAVE FOUND A STRONG ASSOCIATION BETWEEN THE RISK OF DEVELOPING SJS/TEN AND THE PRESENCE OF HLA-B*1502, AN INHERITED ALLELIC VARIANT OF THE HLA-B GENE. HLA-B*1502 IS FOUND ALMOST EXCLUSIVELY IN PATIENTS WITH ANCESTRY ACROSS BROAD AREAS OF ASIA. PATIENTS WITH ANCESTRY IN GENETICALLY AT-RISK POPULATIONS SHOULD BE SCREENED FOR THE PRESENCE OF HLA-B*1502 PRIOR TO INITIATING TREATMENT WITH TEGRETOL. PATIENTS TESTING POSITIVE FOR THE ALLELE SHOULD NOT BE TREATED WITH TEGRETOL UNLESS THE BENEFIT CLEARLY OUTWEIGHS THE RISK (SEE WARNINGS AND PRECAUTIONS, LABORATORY TESTS).
Decision2:
- If genetic testing shows WH is a non-carrier of HLA-B*15:02, then there is a normal or reduced risk of carbamazepine-induced SJS/TEN, and carbamazepine can be used in a standard dose.
- If WH is a carrier of HLA-B*15:02, carbamazepine should not be used�unless the patient has previously used carbamazepine for longer than 3 months without incidence of cutaneous adverse reactions; cautiously consider use of carbamazepine. Otherwise, use an alternative drug.
- Kisor DF, Kane MD, Sprague JE et al. Pharmacogenetics, Kinetics, and Dynamics for Personalized Medicine. Burlingon, MA: Jones & Bartlett Learning; 2014.
- Leckband SG, Kelsoe JR, Dunnenberger HM et al. Clinical pharmacogenetics implementation consortium guidelines for HLA-B genotype and carbamazepine dosing. Clinical Pharmacology & Therapeutics 2013.
Loyd V. Allen, Jr., PhD, RPh
Editor-in-Chief
International Journal of Pharmaceutical Compounding
Remington: The Science and Practice of Pharmacy Twenty-second edition
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