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 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]

Allopurinol is widely prescribed for the treatment of hyperuricemia and gout. An estimated 25-30% of gout patients in the UK and the US are treated with allopurinol. However, 0.1-0.4% of patients treated with allopurinol experience severe cutaneous adverse reactions (SCAR), including drug hypersensitivity syndrome, Stevens-Johnson syndrome, and toxic epidermal necrolysis. The genetic variant HLA-B*58:01, along with non-genetic factors, is known to be associated with this risk. Patients who are HLA-B*58:01-positive (having at least one copy of the HLA-B*58:01 allele) have a significantly increased risk of allopurinol-induced SCAR compared to those who are negative for this allele. It is still possible for a HLA-B*58:01 negative patient to develop SCAR on allopurinol. Guidelines regarding the use of pharmacogenomic tests in dosing for allopurinol have been published in Clinical Pharmacology and Therapeutics by the Clinical Pharmacogenetics Implementation Consortium (CPIC) and are available on the PharmGKB website. [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 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]

Abacavir is a nucleoside reverse transcriptase inhibitor indicated for the treatment of HIV infection, in combination with other medications, as part of highly active antiretroviral therapy. Although abacavir is generally well tolerated, ~5–8% of patients experience a hypersensitivity reaction (HSR) during the first 6 weeks of treatment. Suspicion of an HSR requires immediate discontinuation of abacavir. Drug re-challenge is contraindicated because immediate life-threatening reactions can occur. HLA-B is a member of the major histocompatibility complex gene family and patients with at least one HLA-B*57:01 allele may develop HSR when treated with abacavir. HLA-B allele status has no effect on abacavir pharmacodynamics or pharmacokinetics; it only influences the likelihood that an HSR will occur. Guidelines regarding the use of pharmacogenomic tests in dosing for abacavir have been published in Clinical Pharmacology and Therapeutics by the Clinical Pharmacogenetics Implementation Consortium (CPIC) and are available on the PharmGKB website. [from PharmGKB]