Toxicity of adenine arabinoside in humans

Six forms of reversible adverse reactions to adenine arabinoside (vidarabine) were observed in a two-year period among 42 patients (19 of whom had lymphomas, leukemias, or other malignancies) who were treated for complicated infections with varicella-zoster or herpes simplex virus. Six patients received placebo. Ten patients received 10 mg of adenine arabinoside/kg per day; three received 15 mg/kg; 22 received 20 mg/kg; and one received 30 mg/kg. Patients were treated (by continuous intravenous injection) for an average of seven days. Toxic effects were nausea and vomiting, weight loss, weakness (often with impaired ambulation), megaloblastosis in erythroid series in bone marrow, tremors five to seven days after the start of therapy (including tremors in one patient with abnormal electroencephalograms that were consistent with toxic-metabolic encephalopathy), and thrombophlebitis at the intravenous site. Side effects clearly predominated in patients who received 20 mg/kg per day. Therefore, treatment with 10 mg/kg per day appears preferable until the relation of toxicity to dosage level can be clarified.