Voriconazole Therapy Associated With Hallucinations, Confusion

Among 341 patients, 20 reported experiencing central nervous system symptoms that correlated with voriconazole therapy initiation.
Among 341 patients, 20 reported experiencing central nervous system symptoms that correlated with voriconazole therapy initiation.
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SAN FRANCISCO — Patients receiving voriconazole therapy for the treatment of invasive fungal infections experienced hallucinations and other central nervous system side effects that often resolved after decreasing or discontinuing voriconazole therapy, according to research presented at IDWeek 2018, held October 3-7, 2018, in San Francisco.

Investigators of this retrospective chart review sought to characterize the various side effects — especially those affecting the central nervous system — in adults treated with at least 1 dose of voriconazole for the prevention or treatment of fungal infections.

Researchers screened 341 patients admitted to Duke University hospital from January 1, 2005, to December 31, 2015, who received voriconazole therapy in the form of at least 1 voriconazole serum concentration measurement during their stay. Patient records were further screened to determine whether any central nervous system-related side effects were reported, including hallucinations and visual disturbances, and etiology for the side effects were evaluated for associated with voriconazole.

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Among the 341 patients screened, 20 reported experiencing central nervous system symptoms that correlated with voriconazole therapy initiation; 11 patients who experienced symptoms also received concomitant opioid treatment, which has known side effects of visual hallucinations. The incidence of central nervous system-related side effects included 10 visual hallucinations, 9 visual changes, 2 auditory hallucinations, 2 incidents of confusion, and 3 vivid dreams. The mean voriconazole dose given to patients was 569.0 ± 253.5mg/day or 6.8 ± 2.8mg/kg/day; median time from the first dose to the first documented symptom was 2 days, and symptoms lasted a median duration of 2 days. 

The mean voriconazole serum concentration reported near the time symptoms were first reported was 3.1 ± 2.4mcg/ml. Although symptoms resolved in 4 patients after decreasing voriconazole dosage and in 6 patients after discontinuing therapy, no difference in mean voriconazole serum concentration or total daily dose was determined between patients whose symptoms did or did not resolve. Of note, 10 patients reported no resolution of symptoms after decreased dose voriconazole or discontinuation of therapy.

Experiencing central nervous system side effects during voriconazole therapy is not uncommon, and many patients stopped experiencing symptoms after decreasing or discontinuing voriconazole treatment. Investigators suggested that concomitant opioid use may have contributed to the incidence of central nervous system-related side effects. They also suggest careful consideration before adjusting voriconazole dosage in critically ill patients.

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J.R. Perfect declares associations with Pfizer.

Reference

Mourad A, Johnson M, Perfect JR. Hallucinations and CNS side effects with voriconazole: a real world description. Presented at: IDWeek 2018; October 3, 2018; San Francisco, CA.