ObjectiveTo analyze adverse reaction of voriconazole in Zhejiang province,and provide reference for safe and rational clinical use of it. Methods Eighty-four cases of voriconazole ADR reported from 2013 to 2015 were analyzed in terms of sex,age,mode of administration,time of ADR,combined drug use,organ or system involvement,outcome,etc. Results In the 84 cases of voriconazole ADR,the number of males was higher than that of females,aged 22 to 95 years old,and most cases were more than 60 years of age,accounting for 75.00%.Forty-six cases were caused by intravenous infusion,accounting for 54.76%,31 ADR cases were caused by oral administration,accounting for 36.90%,7 ADR cases were caused by intravenous infusion and oral administration,accounting for 8.33%.In 20 cases,ADR occurred immediately or on the administration day,accounting for 23.81%,and ADR in 36 cases occurred 2 to 10 days after the administration,accounting for 42.86%.The clinical manifestations of ADR were mainly digestive system injury,accounting for 31.58%,and the liver function abnormality was most common,mainly caused by oral administration;visual impairment was the second,accounting for 17.54%,mainly caused by the intravenous infusion;the proportion of nervous system injury was 16.67%,and the proportion of systemic reactions accounted for 11.40%. Conclusion During the period of clinical use,doctors,pharmacists,and nurses should strengthen the propaganda and education,recognition and prevention of voriconazole's ADR.The qualified hospitals may monitor the blood concentration and achieve individualized administration,to reduce the occurrence of ADR.
Key words:
Voriconazole
;
Adverse drug reaction
;
Drug analysis
HICHERI YI,COOKG,CORDONNIERC.Antifungal pro-phylaxis in haematology patients:the role of voriconazole[J].,2012,18(2):1-15.
Abstract Clin Microbiol Infect 2012; 18 (Suppl.2): 1-15 Abstract Invasive fungal infections (IFIs) are a major cause of morbidity and mortality in haematopoietic stem cell transplant (HCT) recipients and patients with haematological malignancies. Early treatment initiation is vital for improving survival, but is hampered by difficulties in timely diagnosis. Prophylaxis with a broad-spectrum antifungal, such as voriconazole, has the potential to decrease the incidence of IFI in haematology patients. Based on a growing body of data, voriconazole appears to be effective for the primary and secondary prevention of IFIs in HCT recipients, with generally good tolerability.
PASCUAL AI,CALANDRAT,BOLAYS,et al.Voricona-zole therapeutic drug monitoring in patients with invasive mycoses improves efficacy and safety outcomes[J].,2008,46(2):201-211.
Background. Voriconazole is the therapy of choice for aspergillosis and a new treatment option for candidiasis. Liver disease, age, genetic polymorphism of the cytochrome CYP2C19, and comedications influence voriconazole metabolism. Large variations in voriconazole pharmacokinetics may be associated with decreased efficacy or with toxicity. Methods. This study was conducted to assess the utility of measuring voriconazole blood levels with individualized dose adjustments. Results. A total of 181 measurements with high-pressure liquid chromatography were performed during 2388 treatment days in 52 patients. A large variability in voriconazole trough blood levels was observed, ranging from 1 mg/L (the minimum inhibitory concentration at which, for most fungal pathogens, 90% of isolates are susceptible) in 25% of cases to > 5.5 mg/L (a level possibly associated with toxicity) in 31% of cases. Lack of response to therapy was more frequent in patients with voriconazole levels ^ 1 mg/L (6 [46%] of 13 patients, including 5 patients with aspergillosis, 4 of whom were treated orally with a median dosage of 6 mg/kg per day) than in those with voriconazole levels > 1 mg/L (15 [12%] of 39 patients; P = .02). Blood levels > 1 mg/L were reached after increasing the voriconazole dosage, with complete resolution of infection in all 6 cases. Among 16 patients with voriconazole trough blood levels > 5.5 mg/L, 5 patients (31%) presented with an encephalopathy, including 4 patients who were treated intravenously with a median voriconazole dosage of 8 mg/kg per day, whereas none of the patients with levels 5.5 mg/L presented with neurological toxicity (P = .002). Comedication with omeprazole possibly contributed to voriconazole accumulation in 4 patients. In all cases, discontinuation of therapy resulted in prompt and complete neurological recovery. Conclusions. Voriconazole therapeutic drug monitoring improves the efficacy and safety of therapy in severely ill patients with invasive mycoses.
LATA,THOMPSON GR.Update on the optimal use of voriconazole for invasive fungal infections[J].,2011,27(4):43-53.
Asma Lat1 George R Thompson III21Department of Pharmacy, New York-Presbyterian Hospital, Columbia University Medical Center, New York, NY, USA; 2Department of Medical Microbiology and Immunology, Coccidioidomycosis Serology Laboratory, and the Department of Medicine, Division of Infectious Diseases, University of California-Davis, Sacramento, CA, USAAbstract: Voriconazole is an extended-spectrum triazole with excellent bioavailability that has now become the treatment of choice for aspergillosis. It has a unique side effect profile compared with other azoles, as well as a number of clinically important drugamp;ndash;drug interactions. These factors, along with a correlation between increased serum levels and improved outcomes, have prompted an interest in therapeutic drug monitoring of this agent. The pharmacology and clinical outcomes data of voriconazole are presented in this review.Keywords: therapeutic drug monitoring, aspergillosis, candidiasis, voriconazole
KINOSHITAJ,IWATAN,OHBAM,et al.Mechanism of voriconazole-induced transient visual disturbances:reversible dysfunction of retinal ON-bipolar cells in monkeys[J].,2011,52(8):5058-5063.
To investigate the mechanism of voriconazole-induced transient visual disturbance in humans.andard full-field electroretinograms (ERGs) were recorded from monkeys treated intravenously with voriconazole. In addition, photopic ERGs elicited by long-duration stimuli (ON-OFF response) were also recorded from monkeys receiving intravenous voriconazole or intravitreal 2-amino-4-phosphonobutyric acid (APB).aracteristic changes were observed in the waveform of the standard full-field ERGs obtained immediately after dosing of voriconazole as follows: electronegative combined rod-cone response (markedly attenuated b-wave and oscillatory potentials), undetectable rod response (eliminated b-wave); slightly abnormal single-flash cone response (flattened appearance in the bottom of the a-wave, mildly attenuated b-wave); and slightly abnormal 30 Hz flicker (mildly attenuated b-wave). The above changes fully recovered to baseline 24 hours after each dosing, along with a decrease in plasma voriconazole concentration. In addition, the change in the waveform of the ON-OFF response recorded in voriconazole-treated monkeys was quite similar to that recorded in APB-treated monkeys as follows: the b-wave was eliminated or prominently attenuated; and the a- and d-waves were not apparently attenuated.The results strongly suggest that voriconazole induces selective and reversible dysfunction of the retinal ON-bipolar cells in both the rod and cone pathways in monkeys. From the results obtained in monkeys in this study, it is suggested that the function of the retinal ON-bipolar cells was selectively and reversibly affected in voriconazole-treated humans who complained of transient visual disturbances.