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Study Details Genetic Influence on Carbamazepine Adverse Reactions

tegretol side effects

 
Carbamazepine (branded as Tegretol) is an anticonvulsant that is used to treat seizures and bipolar disorder among other psychiatric conditions. As effective as the drug is at treating such diseases, patients can suffer from potentially fatal or disfiguring adverse reactions.
 
The primary genetic culprit behind such severe reactions is HLA-B*15:02, according to a recent University of Liverpool study. The findings were published in Pharmacogenomics and Personalized Medicine “The HLA-A*31:01 allele: influence on carbamazepine treatment,” (November 2016).
 

“There is no doubt that there is an association between HLA-A*31:01 and CBZ hypersensitivity, in particular to HSS, in many different ethnic groups,” the authors state, noting that ethnic groups such as Asian population are at greater risk.
 

What is the HLA-B*15:02 Allele?

 

HLA-B*15:02 is an human leukocyte antigen (HLA) allele which is involved in the body’s inflammation response, as encoded by white cells (leukocytes). Specifically, the HLA s is a gene complex encoding the major histocompatibility complex (MHC) proteins in humans. The proteins encoded by certain genes are also known as antigens.

 

Adverse Reactions in Genetically Susceptible Patients

 

Severe adverse reactions can occur in genetically susceptible patients who are administered carbamazepine. Side effects include: toxic epidermal necrolysis (TEN), Stevens–Johnson syndrome (SJS), hypersensitivity syndrome (HSS) and milder reactions, such as maculopapular exanthema (MPE). Such reactions can be severe, life-threatening and disfiguring, the study noted.
 

“The mortality rate of TEN at 1 year is 34%, and in pediatric patients who survived acute TEN, all patients suffered with long-term complications, which included scarring, visual loss and chronic kidney disease,” according to the article.
 

Researchers Call for Pharmacogenetic Screening

 
The study identifies the challenges in applying pharmacogenetic screening for HLA-A*31:01 and proposals for overcoming these barriers. Specifically, the study notes that currently the carbamazepine summary of product characteristics approved by the European Medicines Agency for testing for HLA alleles mandates testing for HLA-B*15:02 before the use of CBZ in certain ethnic groups, but mentions HLA-A*31:01 for information only.
 
“At present, there is a disconnect between health technology assessment and regulatory advice, the authors state. “For precision medicine to succeed, we need to look at all forms of evidence, rather than relying on the usual paradigm of prospective studies or randomized trials.”
 

Understand Your Risks with the Rxight® Genetic Test

 
MD Labs’ Rxight® pharmacogenetic testing is based on the analysis of a comprehensive genetic panel identify whether genetic variants are present that put patients at risk for side effects or medication inefficacy. Over 200 medications across over 50 clinically significant pharmacological classes are tested ( including carbamazepine). All that is required is a simple cheek swab which is sent to our lab for analysis. The results, which are reviewed in detail with patients, are designed to guide prescribers in devising treatment plans that are based in the patient’s unique genotype.

 

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