Patient monitoring and side effects

Response to antifungal therapy in invasive molds is slow and difficult to judge by clinical signs alone. Resolution of fever and eventual clearing of CT scans (in the case of lung infections) are indications of response to antifungal therapy. Toxicity associated with antifungal therapy is similar in these patients as in those described earlier. In addition to the adverse effects mentioned earlier, voriconazole may cause transient visual changes (photopsia) in approximately one-third of patients with the first few doses of therapy. Occasionally, these visual disturbances are accompanied by hallucinations and may require discontinuation of therapy. Voriconazole and posaconazole exhibit wide intrapatient and interpatient pharmacokinetic variability due to variable absorption and metabolism, respectively. 2 Therefore, many experts advocate therapeutic drug monitoring in patients with documented disease receiving the drugs as monotherapy, or in patients with suspected progression (voriconazole, posaconazole) or toxicities (voriconazole) while on therapy. Although the therapeutic ranges are not well established, improved responses in patients receiving posaconazole as salvage therapy have been noted when plasma concentrations 3 to 4 hours after the oral dose approached 1 mcg/mL (1 mg/L).46 For voriconazole, patient response rates are improve if steady-state trough concentrations surpass 1 mcg/mL (1 mg/L); however, the risk of CNS toxicity increases as plasma concentrations increase above 5.5 mcg/mL 47

(5.5 mg/L). Patients often require prolonged therapy, particularly if they remain im-munosuppressed. In many cases, antifungal therapy may be continued indefinitely until complete resolution of underlying immunosuppression.

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