June 2016 THE JAPANESE JOURNAL OF ANTIBIOTICS 69 3 143 19 6 1, 2 1, 2 2 1 1 1 2 1 1 2 2016 4 6 VRCZ VRCZ 4 2 1 68 VRCZ 4 VRCZ VRCZ 2 81 VRCZVRCZ VRCZ 0.09 μg/ml 3 67 VRCZ VRCZ 4 3.79 μg/ml 4 68 VRCZ 42 VRCZ VRCZ 42 1.28 μg/ml 5 76 VRCZ 3 VRCZ VRCZ 3 7.49 μg/ml 6 15 VRCZ 9 VRCZ VRCZ 25 4.45 μg/ml VRCZ VRCZ VRCZ 1 5 μg/ml VRCZ VRCZ
144 20 THE JAPANESE JOURNAL OF ANTIBIOTICS 69 3 June 2016 VRCZ Candida glabrata, Candida krusei 1 3 VRCZ 4 Therapeutic drug monitoring TDM VRCZ TDM 1 2 μg/ml 4 5 μg/ml 5 III VRCZ 78% 6 VRCZ 4,7 6 VRCZ VRCZ 4 2 24 4 28 1 VRCZ 123 VRCZ 15 123 VRCZ 4 2 VRCZ Table 1 VRCZ 1 68 45 kg Candida albicans C. glabrata ITCZ C. albicans VRCZ; Minimum inhibitory concentration MIC 0.125 μg/ml, ITCZ; MIC 0.125 μg/ml, MCFG MIC 0.03 μg/ml, C. glabrata VRCZ; MIC 1 μg/ml, ITCZ; MIC 1 μg/ml, MCFG; MIC 0.03 μg/ml VRCZ VRCZ 1 6.7 mg/kg 300 mg 1 2 2 1 4.4 mg/kg 200 mg 1 2 VRCZ 4 VRCZ MCFG β-d 2 178 pg/ml 64 121 pg/ml VRCZ 4 2 81 50 kg
June 2016 THE JAPANESE JOURNAL OF ANTIBIOTICS 69 3 145 21 Table 1. VRCZ Candida spp. CPFG Candida guilliermondii VRCZ MIC 0.125 μg/ ml, ITCZ; MIC 0.5 μg/ml, MCFG MIC 0.5 μg/ ml VRCZ VRCZ 1 6.0 mg/kg 300 mg 1 2 2 1 4.0 mg/kg 200 mg 1 2 VRCZ VRCZ ITCZ VRCZ VRCZ 0.09 μg/ml 3 67 46 kg Central venous CV 40 C C. albicans VRCZ MIC 0.125 μg/ml, ITCZ;
146 22 THE JAPANESE JOURNAL OF ANTIBIOTICS 69 3 June 2016 0.125 μg/ml, MCFG MIC 0.03 μg/ml Trichosporon asahii VRCZ MIC 0.125 μg/ml, ITCZ; MIC 0.5 μg/ml, MCFG MIC 16 μg/ml VRCZ VRCZ 1 6.5 mg/kg 300 mg 1 2 2 1 4.3 mg/kg 200 mg 1 2 VRCZ VRCZ VRCZ 4 VRCZ 3.79 μg/ ml 4 68 31.5 kg β-d ITCZ β-d B L-AMB VRCZ VRCZ 1 6.3 mg/kg 200 mg 1 2 2 1 3.2 mg/kg 100 mg 1 2 VRCZ 42 ITCZ VRCZ VRCZ 42 1.28 μg/ml 5 76 54.6 kg 0.5 VRCZ VRCZ 1 5.5 mg/kg 300 mg 1 2 2 1 3.7 mg/kg 200 mg 1 2 VRCZ 3 VRCZ 1 2.7 mg/kg 150 mg 1 2 VRCZ VRCZ 3 7.49 μg/ ml 6 15 38.2 kg IgE CT MCFG VRCZ VRCZ 1 5.2 mg/kg 200 mg 1 2 VRCZ 9 VRCZ 19 VRCZ VRCZ 25 4.45 μg/ml VRCZ 1 2.6 mg/kg 100 mg 1 2 VRCZ VRCZ Table 2 VRCZ 3; 3.79 μg/ml 4; 1.28 μg/ml 3.73 μg/ml 0.09 13.27 μg/ml VRCZ
June 2016 THE JAPANESE JOURNAL OF ANTIBIOTICS 69 3 147 23 Table 2. VRCZ 1 2 μg/ml 4 5 μg/ ml VRCZ 5; 7.49 μg/ml 6; 4.45 μg/ml 3.73 μg/ml 0.09 13.27 μg/ml Table 2 VRCZ VRCZ 23 53% 8 VRCZ 4.88% 6/123 VRCZ 4 3.25% 2 1.63% 1 0.81% 1 0.81% VRCZ 0.52% 1.30% 3.25% 4/123 1.63% 2/123 VRCZ VRCZ VRCZ VRCZ 1 7 1 9 6 5 VRCZ 2 9 VRCZ VRCZ 10 VRCZ
148 24 THE JAPANESE JOURNAL OF ANTIBIOTICS 69 3 June 2016 1 μg/ml 7.4 11 6 VRCZ 10,12 VRCZ 12 10 0.46 0.22 1.00 0.36 0.25 0.76 VRCZ VRCZ 3; 3.79 μg/ml 4; 1.28 μg/ml 3.73 μg/ml 0.09 13.27 μg/ml Table 2 VRCZ 5; 7.49 μg/ml 6; 4.45 μg/ml 3.73 μg/ml 0.09 13.27 μg/ml Table 2 VRCZ VRCZ VRCZ VRCZ VRCZ 11 VRCZ 12 VRCZ VRCZ 13 VRCZ VRCZ VRCZ VRCZ VRCZ 12 14 14 VRCZ VRCZ VRCZ VRCZ VRCZ VRCZ VRCZ 1 5 μg/ml VRCZ VRCZ VRCZ VRCZ VRCZ 1
June 2016 THE JAPANESE JOURNAL OF ANTIBIOTICS 69 3 149 25 VRCZ MSD Meiji Seika MSD Meiji Seika 1 EPINEL-INGROFF, A.: In vitro activity of the new triazole voriconazole UK-109,496 against opportunistic filamentous and dimorphic fungi and common and emerging yeast pathogens. J. Clin. Microbiol. 36: 198 202, 1998 2 JOHNSON, L. B. & C. A. KAUFFMAN: Voriconazole: a new triazole antifungal. Clin. Infect. Dis. 36: 630 637, 2003 3 MAESAKI, S.; J. IWAKAWA, Y. HIGASHIYAMA, et al.: Antifungal activity of a new triazole, voriconazole UK-109496 against clinical isolates of Aspergillus spp. J. Infect. Chemother. 6: 101 103, 2000 4 PURKINS, L.; N. WOOD, P. GHAHRAMANI, et al.: Pharmacokinetics and safety of voriconazole following intravenous- to oral-dose escalation regimens. Antimicrob. Agents Chemother. 46: 2546 2553, 2002 5 TDM TDM TDM TDM 60: 429 434, 2012 6 voriconazole 53: 32 50, 2005 7 LAZARUS, H. M.; J. L. BLUMER, S. YANOVICH, et al.: Safety and pharmacokinetics of oral voriconazole in patients at risk of fungal infection; a dose escalation study. J. Clin. Pharmacol. 64: 1997 2020, 2002 8 GHANNOUM, M. A. & D. M. KUHN: Voriconazolebetter chances for patients with invasive mycoses. Eur. J. Med. Res. 7: 242 256, 2002 9 21: 1647 1654, 2005 10 HARIPRASAD, S. M.; W. F. MIELER, E. R. HOLZ, et al.: Determination of vitreous, aqueous, and plasma concentration of orally administered voriconazole in humans. Arch. Ophthalmol. 122: 42 47, 2004 11 TAN, K.; N. BRAYSHAW, K. TOMASZEWSKI, et al.: Investigation of the potential relationship between plasma voriconazole concentration and visual adverse events or liver function test abnormalities. J. Clin. Pharmacol. 46: 235 243, 2006 12 LUTSAR, I.; S. ROFFEY & P. TROKE: Voriconazole concentrations in the cerebrospinal fluid and brain tissue of guinea pigs immunocompromised patients. Clin. Infect. Dis. 37: 728 732, 2003 13 KINOSHITA, J.; N. IWATA, M. OHBA, et al.: Mechanism of voriconazole-induced transient visual disturbance: reversible dysfunction of retinal ON-bipolar cells in monkeys. Invest. Ophthalmol. Vis. Sci. 51: 5058 5063, 2011 14 KAPUR, S.: How antipsychotics become anti- psychotic from dopamine to salience to psychosis. Trends Pharmacol. Sci. 25: 402 406, 2004
150 26 THE JAPANESE JOURNAL OF ANTIBIOTICS 69 3 June 2016 CASE REPORT Visual disturbance or central symptom like hallucination in patients treated voriconazole: report of six cases HIDEO KATO 1,2, MAO HAGIHARA 1,2, YUKIHIRO HAMADA 2, YUSUKE KOIZUMI 1, NAOYA NISHIYAMA 1, YUKA YAMAGISHI 1, KATSUHIKO MATSUURA 2 and HIROSHIGE MIKAMO 1 1 Department of Infection Control and Prevention, Aichi Medical University Hospital, Japan 2 Department of Pharmacy, Aichi Medical University Hospital, Japan Visual disturbance or central symptom like hallucination is well known to be one of the common drug adverse events in response to voriconazole VRCZ We observed 123 patients treated VRCZ from April 2012 to January 2016. Two of these cases experienced visual disturbance and 4 of these cases experienced central symptom. Six patients appeared visual disturbance or central symptom within 1 week after administration of VRCZ visual disturbance; 3 days 2 42 days, central symptom; 6 days 3 9 days and disappeared visual disturbance or central symptom at an early date after discontinuation of administration or decreasing dose of VRCZ. The trough concentration of VRCZ in patients who experienced central symptom was similar with that in patients who did not experience adverse events by VRCZ case 3; 3.79 μg/ ml, case 4; 1.28 μg/ml vs 3.73 μg/ml 0.09 13.27 μg/ml On the other hand, the trough concentration of VRCZ in patients who experienced visual disturbance was higher than that in patients who did not experience adverse events by VRCZ case 5; 7.49 μg/ml, case 6; 4.45 μg/ ml vs 3.73 μg/ml 0.09 13.27 μg/ml In conclusion, we thought that the risk factor of visual disturbance was the increasing concentration of VRCZ. Therefore, we should monitor the onset of visual disturbance or central symptom in patients treated with VRCZ, especially central symptom that the concentration is unconcerned.