MedGen

Carbamazepine is an aromatic anticonvulsant used to treat epilepsy and other seizure disorders, as well as bipolar disorder and trigeminal neuralgia. Carbamazepine can cause a variety of cutaneous adverse reactions, ranging from mild maculopapular eruptions to Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). The genetic variants HLA-B*15:02 and HLA-A*31:01 are associated with the risk of SJS/TEN. Patients who have at least one copy of the HLA-B*15:02 or HLA-A*31:01 allele (considered HLA-B*15:02 positive or HLA-A*31:01-positive, respectively) have a significantly increased risk for SJS/TEN compared to non-carriers, and it is recommended that they receive an alternate drug. It is important to note that it is possible for a patient without HLA-B*15:02 to develop SJS/TEN. Guidelines regarding the use of pharmacogenomic tests in dosing for carbamazepine have been published in Clinical Pharmacology and Therapeutics by the Clinical Pharmacogenetics Implementation Consortium (CPIC) and are available on the CPIC and PharmGKB websites. [from PharmGKB]

Carbamazepine is an aromatic anticonvulsant used to treat epilepsy and other seizure disorders, as well as bipolar disorder and trigeminal neuralgia. Carbamazepine can cause a variety of cutaneous adverse reactions, ranging from mild maculopapular eruptions to Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). The genetic variant HLA-B*15:02 is associated with the risk of SJS/TEN. Patients who have at least one copy of the HLA-B*15:02 allele (considered HLA-B*15:02-positive) have a significantly increased risk for SJS/TEN compared to non-carriers, and it is recommended that they receive an alternate drug. It is important to note that it is possible for a patient without HLA-B*15:02 to develop SJS/TEN. Guidelines regarding the use of pharmacogenomic tests in dosing for carbamazepine have been published in Clinical Pharmacology and Therapeutics by the Clinical Pharmacogenetics Implementation Consortium (CPIC) and are available on the PharmGKB website. [from PharmGKB]

Dabrafenib is a kinase inhibitor used in the treatment of individuals with unresectable or metastatic melanoma, metastatic non-small cell lung cancer (NSCLC), locally advanced or metastatic anaplastic thyroid cancer (ATC), pediatric low-grade glioma (LGG), and other unresectable or metastatic solid tumors with specific BRAF variants. Dabrafenib can be used as a single agent to treat melanoma with the BRAF valine 600 to glutamic acid (V600E) variant or in combination with the MEK inhibitor trametinib to treat multiple tumor types with BRAF V600E or V600K variants.The BRAF protein is an intracellular kinase in the mitogen-activated protein kinases (MAPK) pathway. Functionally, BRAF regulates essential cell processes such as cell growth, division, differentiation, and apoptosis. The gene BRAF is also a proto-oncogene—when mutated, it transforms normal cells into cancerous cells. Variation in the kinase domain of BRAF is associated with various cancers. The most common BRAF variant, V600E, constitutively activates the kinase and causes cell proliferation in the absence of growth factors that would usually be needed. The V600E variant is detected in approximately 50% of melanomas, 25% of ATC, 2% of NSCLC, and 20% of pediatric LGGs. The FDA-approved label for dabrafenib states that the presence of BRAF mutation in tumor specimens (V600E for dabrafenib monotherapy; V600E or V600K for dabrafenib plus trametinib) should be confirmed using an FDA-approved test before starting treatment with dabrafenib. Dabrafenib is not indicated for the treatment of individuals with wild-type BRAF tumors, or the treatment of colorectal cancer due to intrinsic resistance to BRAF inhibitor monotherapy. The label also states that individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency should be monitored for signs of hemolytic anemia while taking dabrafenib (1). However, it is important to note that an independent literature review by the Clinical Pharmacogenetics Implementation Consortium found no publications to support or refute this risk and thus issued no guidance for G6PD deficiency and dabrafenib therapy. [from Medical Genetics Summaries]