Feng, Xiaodong_ Xie, Hong-Guang - Applying pharmacogenomics in therapeutics-CRC Press (2016)

Concepts in Pharmacogenomics and Personalized Medicine
15
Test Availability and Recommendations
A simple HLA typing will indicate whether patients are positive for the HLA-
B*1502; patients are positive if either one or two alleles of HLA-B*1502 are present.
In 2007, the US FDA recommended that all patients of Asian descent be screened
for the HLA-B*1502 allele before initiating carbamazepine therapy. This recommendation
is also reflected in the black box warning in the prescribing information
of carbamazepine. 30 Therefore, prior to initiation of this drug in high-risk patients,
genotyping is recommended.
It is important to note that patients who have been treated with carbamazepine
for an extended period do not need testing of the HLA-B*1502 allele. The SJS/TEN
reactions generally occur within the first two months of treatment, and the risk for
developing HSR is considered to be low even among carriers of the HLA-B*1502
status. 92 However, patients who are negative for the HLA-B*1502 allele and receive
carbamazepine should still be monitored clinically for the development of HSRs
since other genetic and nongenetic factors may contribute to these ADRs.
Clinical Pharmacogenetics Implementation Consortium (CPIC) published a guidance
for use and dosing of carbamazepine in patients who are carriers and noncarriers
of HLA-B*1502. 105 They recommend that in carriers of the HLA-B*1502,
carbamazepine should not be used in those who are new to the drug. In those who
have previously used carbamazepine for longer than three months without any
adverse effects, the drug can be used with caution.
TOXICITY: CODEINE
Clinical Case
A 55-year-old man is being evaluated for chronic back pain that he has been suffering
from for the past five years. He has tried multiple medications, including
anti-inflammatory drugs, opiates, and anticonvulsants with little relief. He is considering
surgical options for his chronic back pain because he does not want to become
“dependent” on his medications, and he has had numerous side effects from his
medications.
Background
Codeine is a weak opiate agonist that is used to treat mild-to-moderate pain. 106 In
order to exert its efficacy, it must be converted to its active metabolite, morphine,
via cytochrome P450 2D6 (CYP2D6). 107–109 It is often combined with other analgesics,
such as acetaminophen, for mild-to-moderate pain disorders and postsurgical
analgesia.
Gene/Allele of Interest and Functional Effect
The interindividual variability of CYP2D6 enzyme activity can be explained, in
part, by the genetic variation of CYP2D6. 110–112 Genetic polymorphisms of CYP2D6