Methods: We conducted a retrospective chart review to select adult patients who had received at least one dose of voriconazole and had at least one voriconazole serum concentration measurement during admission at Duke University Hospital between 01/01/2005 – 12/31/2015. The records were then screened to determine if patients experienced CNS side effects while on voriconazole and determined whether these effects were drug related.
Results: Of the 341 patients screened, 20 had documented CNS symptoms that were associated with the start of voriconazole therapy. 65% were male, 80% were Caucasian and mean age was 55.8 ± 13.3 years. Mean voriconazole dose was 569.0 ± 253.5 mg/day, 6.8 ± 2.8 mg/kg/day. The incidences of CNS symptoms were: 10 visual hallucinations, 9 visual changes, 2 auditory hallucinations, 2 confusions and 3 vivid dreams. Median time from first dose to first documented symptoms was 2 days (IQR 0-9), and median duration of symptoms was 2 days (IQR 1-6). Mean voriconazole serum concentration closest to when the first symptoms were documented was 3.1 ± 2.4 mcg/ml. Symptoms resolved after decreasing dose or discontinuing voriconazole in 4 and 6 patients, respectively. Symptoms did not resolve in 10 (50%) patients during admission. There was no difference in mean voriconazole concentration or total daily dose between patients whose symptoms did or did not resolve. 11 (55%) patients were receiving concomitant opioids when they experienced their symptoms.
Conclusion: CNS side effects of voriconazole are not rare but a large number of patients will have resolution of these symptoms after decreasing or discontinuing voriconazole. Concomitant opioids may be contributing to the incidence of these side effects since they can be associated with similar symptoms. It is important to consider all potential causes of CNS symptoms before making unnecessary voriconazole dose adjustments in critically ill patients.
J. R. Perfect, Pfizer: Consultant and Scientific Advisor , Research grant .