Zidovudine intolerance

Patients may be intolerant of zidovudine for several reasons, the most prominent being hematologic toxicity. In vitro studies demonstrate that zidovudine is toxic to the myeloid and erythroid precursors in the bone marrow; at concentrations of zidovudine near those associated with the optimal antiviral effect in vitro, the proliferative capability of these progenitor cells is reduced 50%-70%. The clinical manifestations of anemia and leukopenia generally are time- and dose-dependent. Strategies for alleviating the hematologic toxicity of zidovudine include the use of hematopoietic growth factors, such as erythropoietin, granulocyte colony-stimulating factor, or granulocyte-macrophage colony-stimulating factor. Myopathy, a recently recognized toxic effect of zidovudine, also appears to be time-dependent. Patients often complain of muscle weakness and discomfort and exhibit an associated elevation in creatine phosphokinase level; dose reduction or discontinuation of therapy generally is required. Some patients have experienced high fever, nausea, and vomiting; however, these effects are unusual and of unclear etiology. The substantial proportion of patients with AIDS or AIDS-related complex receiving zidovudine who experience hematologic or muscular toxicity may benefit from treatment with new antiviral agents, such as dideoxyinosine, with toxicity profiles different from that of zidovudine.