Hypersensitivity reactions during therapy with the nucleoside reverse transcriptase inhibitor abacavir

Background: Hypersensitivity reactions consist of a variable group of clini cal findings and have been described for a wide variety of chemical compoun ds. Objective: This review characterizes the clinical profile of hypersensitivi ty to the nucleoside reverse transcriptase inhibitor abacavir sulfate. Methods: We performed a retrospective medical review of pooled adverse even ts data from similar to 200,000 patients who received abacavir in clinical trials, through expanded-access programs, or by prescription from 1996 thro ugh 2000. Screened cases of hypersensitivity were classified as either defi nitive or probable. Definitive cases were identified when initial symptoms resolved on interruption of abacavir therapy and returned on reintroduction of abacavir therapy. Results: A total of 1803 cases were identified, 1302 in the 30,595 patients participating in clinical trials or the expanded-access program and 501 in patients from the postmarketing experience. On review, 176 (9.8%) of these cases were considered definitive and the remainder probable. Based on the 1302 cases identified in clinical trials or the expanded-access program, th e calculated incidence of hypersensitivity was 4.3%. Symptoms reported in g reater than or equal to 20% of cases of this multiorgan reaction included f ever, rash, malaise/fatigue, and gastrointestinal symptoms such as nausea, vomiting, and diarrhea, among others. Respiratory symptoms occurred in 30% of cases and included dyspnea (12%), cough (10%), and pharyngitis (6%). In 90% of cases, hypersensitivity reactions occurred within the first 6 weeks after initiation of abacavir (median time, I I days); after an initial reac tion, rechallenge with abacavir resulted in the reappearance of symptoms wi thin hours of reexposure. Hypotension was present in 25% of these rechallen ge reactions. Among patients who received abacavir in clinical trials, the mortality rate was 0.03% (3 per 10,000 patients). Conclusions: Hypersensitivity to abacavir is an idiosyncratic reaction and a distinct clinical syndrome characterized predominantly by systemic involv ement. It can be expected to appear as a treatment-limiting event in simila r to5% of patients. The appearance of clinical symptoms consistent with thi s syndrome mandates immediate discontinuation of abacavir. Hypersensitivity to abacavir is an absolute contraindication to subsequent treatment with a ny formulation that includes this agent.