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Test ID: CARPO Carbamazepine Hypersensitivity Pharmacogenomics, Saliva

Useful For

Identifying individuals with increased risk of carbamazepine-associated cutaneous adverse reactions

 

Identifying individuals who may be at increased risk of cutaneous adverse reactions when treated with alternative medications to carbamazepine including phenytoin, fosphenytoin, oxcarbazepine, eslicarbazepine acetate, and lamotrigine

 

Genotyping patients who prefer not to have their blood drawn

Method Name

Qualitative Allele-Specific Real-Time Polymerase Chain Reaction (PCR)

Reporting Name

Carbamazepine PGx Panel, Saliva

Specimen Type

Saliva


Specimen Required


Multiple saliva genotype tests can be performed on a single specimen after a single extraction. See Multiple Saliva Genotype Tests in Special Instructions for a list of tests that can be ordered together.

 

Container/Tube: Oragene DNA Self-Collection Kit (T651: fees apply)

Specimen Volume: Full tube

Collection Instructions:

1. Fill tube to line.

2. Send specimen in original container per kit instructions.


Specimen Minimum Volume

1 mL

Specimen Stability Information

Specimen Type Temperature Time
Saliva Ambient

Clinical Information

Carbamazepine is sometimes prescribed for the treatment of epilepsy, as well as trigeminal neuralgia and bipolar disorder. A minority of carbamazepine-treated persons have cutaneous adverse reactions that vary in prevalence and severity, with some forms associated with substantial morbidity and mortality. More severe reactions, such as the hypersensitivity syndrome, are associated with mortality of up to 10% and include symptoms such as rash, fever, eosinophilia, hepatitis, and nephritis. The most severe reactions, such as the Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), are characterized by a blistering rash affecting a variable percentage of the body-surface area. TEN is the rarest of these phenotypes and is associated with mortality of up to 30%. According to the FDA-approved label for carbamazepine, the estimated incidence of SJS-TEN is 1 to 6 cases in 10,000 persons of European ancestry who are exposed to the drug. The rate of SJS-TEN as a result of carbamazepine exposure is about 10 times higher in some Asian countries.

 

Clinical studies have demonstrated associations between some human leukocyte antigen (HLA) genotypes and drug-associated cutaneous adverse reactions. The presence of the HLA-B*15:02 allele varies throughout Asia: 10% to 15% frequency in Chinese, 2% to 4% frequency in Southeast Asians, including Indians, and <1% frequency in Japanese and Koreans.

 

The HLA-A*31:01 allele, which has a prevalence of 2% to 5% in Northern European populations, has been significantly associated with drug-associated cutaneous adverse reactions. In the absence of HLA-A*31:01, the risk for drug-associated cutaneous adverse reactions is 3.8%, but in the presence of this allele, the risk increases to 26%.  

 

The FDA-approved label for carbamazepine states that the screening of patients in genetically at-risk populations (ie, patients of Asian descent) for the presence of the HLA-B*15:02 allele should be carried out prior to initiating treatment with carbamazepine. The FDA-approved label also notes the association of HLA-A*31:01 allele with drug-associated cutaneous adverse reactions regardless of ethnicity but does not specifically mandate screening of patients. For patients who are HLA-B*15:02 and HLA-A*31:01 positive, oxcarbazepine, phenytoin, fosphenytoin, eslicarbazepine acetate, and lamotrigine may also be associated with drug-associated cutaneous adverse reactions so these medications may need to be avoided as well.

Reference Values

An interpretive report will be provided.

Interpretation

The presence of the HLA-B*15:02 and/or HLA-A*31:01 allele confers increased risk for hypersensitivity to carbamazepine.

 

For additional information regarding pharmacogenomic genes and their associated drugs, see the Pharmacogenomic Associations Tables in Special Instructions. This resource also includes information regarding enzyme inhibitors and inducers, as well as potential alternate drug choices.

Clinical Reference

1. Leckband SG, Kelsoe JR, Dunnenberger HM, et al: Clinical Pharmacogenetics Implementation Consortium guideline for HLA-B genotype and carbamazepine dosing. Clin Pharmacol Ther 2013;94(3):324-328

2. Caudle KE, Rettie AE, Whirl-Carrillo M, et al: Clinical pharmacogenetics implementation consortium guidelines for CYP2C9 and HLA-B genotypes and phenytoin dosing. Clin Pharacol Ther. 2014;96(5):542-548

3. McCormack M, Alfirevic A, Bourgeois S, et al: HLA-A*3101 and carbamazepine-induced hypersensitivity reactions in Europeans. N Engl J Med 2011;364:1134-1143

4. Amstutz U, Shear NH, Rieder MJ, et al: Recommendations for HLA-B*15:02 and HLA-A*31:01 genetic testing to reduce the risk of carbamazepine-induced hypersensitivity reactions. Epilepsia 2014;55:496-506 

Day(s) and Time(s) Performed

Monday, Thursday

Analytic Time

1 day (not reported on Saturday or Sunday)

Test Classification

This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the U.S. Food and Drug Administration.

CPT Code Information

81381 x 2

LOINC Code Information

Test ID Test Order Name Order LOINC Value
CARPO Carbamazepine PGx Panel, Saliva In Process

 

Result ID Test Result Name Result LOINC Value
37300 HLA-A3101 Genotype In Process
37301 HLA-B1502 Genotype In Process
37302 Carbamazepine PGx Panel Phenotype In Process
37303 Carbamazepine PGx Panel Interpretation In Process
37408 Reviewed by No LOINC Needed

Forms

New York Clients-Informed consent is required. Please document on the request form or electronic order that a copy is on file. An Informed Consent for Genetic Testing (T576) is available in Special Instructions.

Mayo Medical Laboratories | Genetics and Pharmacogenomics Catalog Additional Information:

mml-pgx