Abacavir is a nucleoside reverse transcriptase inhibitor (NRTI) used in the treatment of infection caused by the human immunodeficiency virus (HIV). There are two licensed products carrying abacavir namely Ziagen® (GlaxoSmithKline), which contains abacavir only and Kivexa® (GlaxoSmithKline) which contains a combination of abacavir and lamivudine.
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HLA-B*5701 associated Abacavir Hypersensitivity Reactions (HSR)
Recently, the US Food and Drug Administration (FDA) issued an alert informing healthcare professionals that serious and sometimes fatal hypersensitivity reactions caused by abacavir therapy are significantly more common in patients with the human leukocyte antigen (HLA) allele, HLA-B*5701. This alert was based on the review of 2 studies, PREDICT-1 and SHAPE, which supported the recommendation for pre-therapy screening for the presence of HLA-B*5701 allele and the selection of alternative therapies in positive subjects.
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Abacavir Hypersensitivity Reactions
Abacavir HSR is a multi-organ syndrome characterized by two or more clinical signs and symptoms that include fever, rash, gastrointestinal symptoms, respiratory symptoms and constitutional symptoms. Symptoms can occur any time during treatment with abacavir but usually appear within the first 6 weeks (median, 11 days).
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Details of the studies
PREDICT-1 is a prospective, randomized, double-blind study that evaluates the clinical utility of pre-therapy HLA-B*5701 screening compared to no screening on the incidence of abacavir HSR in abacavir-naïve patients infected with HIV type 1. Data from PREDICT-1 estimates that 61%of HLA-B*5701 positive subjects will develop abacavir HSR during treatment with abacavir compared with 4.5% of HLA-B*5701 negative subjects. Screening of HIV-1 infected subjects for the presence of HLA-B*5701 resulted in a reduction in the incidence of clinically-suspected HSR of approximately 60% compared with no screening.
The SHAPE study is a retrospective, case-control study designed to evaluate the sensitivity of HLA-B*5701 allele with respect to abacavir HSR in black and white subjects in the United States. In this study, the data supports the strong association between HLA-B*5701 and clinically-suspected abacavir HSR in both black and white patients as well as the pre-screening for the HLA-B*5701 allele in the broader United States population to improve the safety profile of abacavir.
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International regulatory actions
Following the safety alert by FDA, the US package inserts of abacavir and abacavir-containing medications were updated to include recommendation to test patients for HLA-B*5701 allele before starting or restarting these medications. The US abacavir medication guide for patients was also updated to highlight the safety information on the increase risk of abacavir HSR in patients with the HLA-B*5701 allele carriage. Similar warnings on strong association between HLA-B*5701 allele carriage and abacavir HSR and the recommendation to do pre-therapy HLA-B*5701 screening have also been updated in the European package inserts for abacavir containing medications.
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Local situation
HSA has not received any local reports pertaining to abacavir HSR. However, physicians who prescribe abacavir-containing medications are encouraged to advise their patients to look out for signs and symptoms of abacavir hypersensitivity reactions. If they develop signs and symptoms suggestive of hypersensitivity reactions, they should be advised to stop their medication and seek prompt medical attention. Although our Asian population has a low prevalence of the HLA-B*5701 allele, it is important to bear in mind the potential risk of abacavir HSR associated with this allele.
The local package insert for Ziagen® has recently been updated to reflect the safety information on HLA-B*5701 allele associated abacavir HSR and the recommendation to do pre-therapy screening for this allele. The package insert of Kivexa® is in the process of being updated with this safety information. Healthcare professionals are encouraged to report suspected adverse drug reactions associated with abacavir to the Pharmacovigilance Branch of HSA.
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References
- FDA alert. Information for Healthcare Professionals Abacavir (marketed as Ziagen) and Abacavir-containing Medications. http://www.fda.gov/cder/drug/InfoSheets/HCP/abacavirHCP.htm.
- European Public Assessment Report for Abacavir (Ziagen®) http://www.emea.europa.eu/humandocs/PDFs/EPAR/Ziagen/101999en8b.pdf.
- N Eng J Med 2008 Feb 7;358:568-79
- CID 2008 Apr 1; 46: 1111-8
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