Hypersensitivity reactions during therapy with the nucleoside reverse transcriptase inhibitor abacavir

Hetherington, Seth; McGuirk, Sue; Powell, Gwendolyn; Cutrell, Amy; Naderer, Odin; Spreen, Bill; Lafon, Steve; Pearce, Gillian; Steel, Howard H.

doi:10.1016/s0149-2918(01)80132-6

Cited by 389 publications

(280 citation statements)

References 29 publications

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“…Hypersensitivity to abacavir occurs in approximately 5-8% of patients within 1-6 weeks of the initial dose. 35 The initial association between abacavir-induced hypersensitivity and HLA-B*5701 was reported in Australian and British populations. 36,37 However, abacavir-induced hypersensitivity is present at a high frequency only in Caucasians and at a very low frequency in Asian and black populations.…”

Section: Abacavirmentioning

confidence: 99%

Pharmacogenetics of cutaneous adverse drug reactions

Aihara

2011

The Journal of Dermatology

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Drug-induced hypersensitivity reactions are of major medical concern because they are associated with high morbidity and high mortality. In addition, individual patients' reactions are impossible to predict in each patient. In the field of severe cutaneous adverse drug reactions (cutaneous ADR) such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug-induced hypersensitivity syndrome (DHIS) or drug rash with eosinophilia and systemic symptoms (DRESS), major advances have recently been gained through studies of an association between HLA alleles and drug hypersensitivity induced by specific drugs. The results of these pharmacogenomic studies allow prediction of the risk of adverse reactions in patients treated with certain drugs, including carbamazepine and other aromatic antiepileptic drugs, allopurinol and abacavir. However, different ethnic populations show variations in the genetic associations. A strong association between carbamazepine-induced SJS ⁄ TEN and HLA-B*1502 has been found in Southeast Asian patients but not in Caucasian and Japanese patients. Moderate associations between aromatic amine anticonvulsants and other HLA alleles have been proposed in Japanese patients. In contrast, HLA-B*5801 was found to be associated with allopurinol-induced cutaneous ADR, including SJS ⁄ TEN and DIHS ⁄ DRESS, in Caucasian and Asian patients, including the Japanese. These differences may, at least in part, be due to the differences in allele frequency in different ethnic populations. This article reviews the progress in pharmacogenomics, associated mainly with carbamazepine and allopurinol in different ethnic populations. Pharmacogenetic screening based on associations between adverse reactions and specific HLA alleles helps to avoid serious conditions associated with drug hypersensitivity.

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Section: Abacavirmentioning

confidence: 99%

Pharmacogenetics of cutaneous adverse drug reactions

Aihara

2011

The Journal of Dermatology

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“…Abacavir is prescribed for the treatment of HIV and, although well-tolerated, approximately 5% of the population is at risk of developing hypersensitivity (HSR) to the drug [70]. Within the first 11 days of abacavir use, individuals with drug hypersensitivity may present with fever, skin rash, gastrointestinal or respiratory problems, and in rare cases, lifethreatening conditions like Stevens-Johnson syndrome (SJS) [66,70]. In 2002, the genetic susceptibility of HSR was determined, when the HLA-B locus variant, HLA-B*5701, was shown to be associated with increased risk of developing HSR in response to abacavir [71].…”

Section: Immune-mediated Responsesmentioning

confidence: 99%

Application and Utility of Pharmacogenetics in the Clinical Laboratory

2014

J Analyt Molecul Tech

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The administration of pharmaceuticals presents a challenge for the healthcare system, as inappropriate drug or dose selection can result in diminished therapeutic efficacy or adverse drug reactions. Genetic variability is a major regulator of drug action and should be taken into account during drug and dose selection. The correlation of drug responses (phenotypes) to specific polymorphisms (genotype) has contributed to the development of many targeted genotyping approaches. Incorporation of such testing into the clinical laboratory requires the evaluation of current testing platform characteristics as well as the selection of appropriate polymorphisms to be tested. Here we describe known genotype -phenotype relationships pertinent to drug action and present currently available targeted genotyping platforms for pharmacogenetics (PGx) testing. We additionally discuss considerations regarding platform and polymorphism selection for successful integration of PGx testing into the clinical laboratory and attainment of clinically useful results.

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“…Abacavir (ABC) is widely prescribed as part of the HAART regimen although about 5-8% of Caucasian patients who receive ABC develop a HSR within the first 6 weeks of treatment [70,71]. Symptoms include fever, rash, gastrointestinal disturbances, and lethargy.…”

Section: Pharmacogenetics Of Abacavirmentioning

confidence: 99%

The Pharmacogenetics of HIV Treatment: A Practical Clinical Approach

Barc¹

2013

J Pharmacogenom Pharmacoproteomics

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Hypersensitivity reactions during therapy with the nucleoside reverse transcriptase inhibitor abacavir

Cited by 389 publications

References 29 publications

Pharmacogenetics of cutaneous adverse drug reactions

Pharmacogenetics of cutaneous adverse drug reactions

Application and Utility of Pharmacogenetics in the Clinical Laboratory

The Pharmacogenetics of HIV Treatment: A Practical Clinical Approach

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