Abacavir - Side Effects

Side Effects

Fatal hypersensitivity reactions have been associated with therapy with abacavir. Symptoms of hypersensitivity include fever, skin rash, fatigue, gastrointestinal symptoms such as nausea, vomiting, diarrhea or abdominal pain and respiratory symptoms such as pharyngitis, dyspnea, or cough.

Hypersensitivity is strongly associated with HLA-B*57:01 for which testing is now available in most western countries. There is a strong relationship with race: the prevalence of HLA-B*57:01 in some Indian ethnic groups is up to 10%, but is 0% in Japan; the prevalence is 5–7% in western Europe. Screening for the HLA-B*57:01 has been convincingly shown to reduce the incidence of abacavir hypersensitivity reactions. Abacavir binds specificially to the peptide-binding groove of HLA-B*57:01 and thereby alters the spectrum of peptides that bind to this molecule. This in turn leads to aberrant CD8 T-cell responses to self-antigens, which probably explain the side effect.

A new FDA alert concerning abacavir and abacavir containing medications was issued on July 24, 2008. FDA informed that based on data from two studies they support a recommendation for pre-therapy screening for the presence of the HLA-B*57:01 allele and the selection of alternative therapy in positive subjects. Genetic tests for HLA-B*57:01 are available and all patients should be screened for the HLA-B*57:01 allele before starting or restarting treatment with abacavir or abacavir containing medications. Development of clinically suspected abacavir HSR requires immediate and permanent discontinuation of abacavir therapy in all patients, including patients negative for HLA-B*57:01. On March 1, 2011 the FDA updated the public about an ongoing safety review of abacavir and a possible increased risk of heart attack.