Voriconazole Therapeutic Drug Monitoring is Necessary for Children with Invasive Fungal Infection
1
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Purpose: To determine the clinical significance of voriconazole therapeutic drug monitoring (TDM) in the pediatric population. Methods: Twenty-eight patients with invasive fungal infections administered with voriconazole from July 2010 to June 2012were investigated retrospectively. Fourteen received TDM, and 143 trough concentrations were analyzed. All 28 patientswere assessed for adverse events and treatment response six weeks into treatment, and at the end. Results: Out of 143 samples, 53.1% were within therapeutic range (1.0-5.5 mg/L). Patients administered with the same loading(6 mg/kg/dose) and maintenance (4 mg/kg/dose) dosages prior to initial TDM showed highly variable drug levels. Adverseevents occurred in 9 of 14 patients (64.3%) in both the TDM and non-TDM group. In the TDM group, voriconazole-relatedencephalopathy (n=2, 14.3%) and aspartate aminotransferase (AST) or alanine aminotransferase (ALT) elevation (n=8, 57.1%) occurred with serum levels in the toxic range (>5.5 mg/L), whereas blurred-vision (n=2, 14.3%) occurred within thetherapeutic range (1.18 mg/L and 3.9 mg/L). The frequency of voriconazole discontinuation due to adverse events waslower in the TDM group (0.0% vs. 18.2%, P =0.481). Overall, 57.2% of the patients in the TDM group versus 14.3% in thenon-TDM group showed clinical response after 6 weeks (P =0.055), whereas 21.4% in the TDM group versus 14.3% in thenon-TDM group showed response at final outcome (P =0.664). In the TDM group, >67.0% of the serum levels were withintherapeutic range for the first 6 weeks; however 45.5% were within therapeutic range for the entire duration. Conclusion: Routine TDM is recommended for optimizing the therapeutic effects of voriconazole.
Abstract
Purpose: To determine the clinical significance of voriconazole therapeutic drug monitoring (TDM) in the pediatric population. Methods: Twenty-eight patients with invasive fungal infections administered with voriconazole from July 2010 to June 2012were investigated retrospectively. Fourteen received TDM, and 143 trough concentrations were analyzed. All 28 patientswere assessed for adverse events and treatment response six weeks into treatment, and at the end. Results: Out of 143 samples, 53.1% were within therapeutic range (1.0-5.5 mg/L). Patients administered with the same loading(6 mg/kg/dose) and maintenance (4 mg/kg/dose) dosages prior to initial TDM showed highly variable drug levels. Adverseevents occurred in 9 of 14 patients (64.3%) in both the TDM and non-TDM group. In the TDM group, voriconazole-relatedencephalopathy (n=2, 14.3%) and aspartate aminotransferase (AST) or alanine aminotransferase (ALT) elevation (n=8, 57.1%) occurred with serum levels in the toxic range (>5.5 mg/L), whereas blurred-vision (n=2, 14.3%) occurred within thetherapeutic range (1.18 mg/L and 3.9 mg/L). The frequency of voriconazole discontinuation due to adverse events waslower in the TDM group (0.0% vs. 18.2%, P =0.481). Overall, 57.2% of the patients in the TDM group versus 14.3% in thenon-TDM group showed clinical response after 6 weeks (P =0.055), whereas 21.4% in the TDM group versus 14.3% in thenon-TDM group showed response at final outcome (P =0.664). In the TDM group, >67.0% of the serum levels were withintherapeutic range for the first 6 weeks; however 45.5% were within therapeutic range for the entire duration. Conclusion: Routine TDM is recommended for optimizing the therapeutic effects of voriconazole.
참고문헌 (28)
- Ascioglu S, "Defining opportunistic invasive fungal infections in immunocompromised patients with cancer and hematopoietic stem cell transplants: an international consensus", Clin Infect Dis, 34, pp.7~14 (2002)
- Pfaller MA, "Invasive fungal pathogens:current epidemiological trends", Clin Infect Dis, 43, pp.S3~S14 (2006)
- Ashley ESD, "Pharmacology of systemic antifungal agents", Clin Infect Dis, 43, pp.S28~S39 (2006)
- Herbrecht R, "Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis", N Engl J Med, 347, pp.408~415 (2002)
- De Pauw B, "Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer", Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC, Clin Infect Dis, pp.2008, 46[DOI]
- Kauffman CA, "The changing landscape of invasive fungal infections: epidemiology, diagnosis, and pharmacologic options", Clin Infect Dis, 43, pp.S1~S2 (2006)
- Purkins L, "Pharmacokinetics and safety of voriconazole following intravenous- to oral-dose escalation regimens", Antimicrob Agents Chemother, 46, pp.2546~2553 (2002)
- Walsh TJ, "Pharmacokinetics and safety of intravenous voriconazole in children after single- or multiple-dose administration", Antimicrob Agents Chemother, 48, pp.2166~2172 (2004)
- Lat A, "Update on the optimal use of voriconazole for invasive fungal infections", Infect Drug Resist, 4, pp.43~ (2011)
- Walsh TJ, "Pharmacokinetics, safety, and tolerability of voriconazole in immunocompromised children", Antimicrob Agents Chemother, 54, pp.4116~4123 (2010)
- Segal BH, "Defining responses to therapy and study outcomes in clinical trials of invasive fungal diseases: Mycoses Study Group and European Organization for Research and Treatment of Cancer consensus criteria", Clin Infect Dis, 47, pp.674~683 (2008)
- Neely M, "Voriconazole pharmacokinetics and pharmacodynamics in children", Clin Infect Dis, 50, pp.27~36 (2010)
- Pascual A, "Voriconazole therapeutic drug monitoring in patients with invasive mycoses improves efficacy and safety outcomes", Clin Infect Dis, 46, pp.201~211 (2008)
- "National Cancer Institute" (2013)[URL]
- Taketomo CK, "Pediatric Dosage Handbook", pp.1274~1276 (2009), Lexi-Comp, Inc
- Singh N, "Treatment of opportunistic mycoses: how long is long enough?", Lancet Infect Dis, 3, pp.703~708 (2003)
- Park WB, "The effect of therapeutic drug monitoring on safety and efficacy of voriconazole in invasive fungal infections: a randomized controlled trial", Clin Infect Dis, 55, pp.1080~1087 (2012)
- Troke PF, "Observational study of the clinical efficacy of voriconazole and its relationship to plasma concentrations in patients", Antimicrob Agents Chemother, 55, pp.4782~4788 (2011)
- Ueda K, "Monitoring trough concentration of voriconazole is important to ensure successful antifungal therapy and to avoid hepatic damage in patients with hematological disorders", Int J Hematol, 89, pp.592~599 (2009)
- Choi SH, "Importance of voriconazole therapeutic drug monitoring in pediatric cancer patients with invasive aspergillosis", Pediatr Blood Cancer, 60, pp.82~87 (2013)
- Soler-Palacin P, "Voriconazole drug monitoring in the management of invasive fungal infection in immunocompromised children: a prospective study", J Antimicrob Chemother, 67, pp.700~706 (2012)
- Michael C, "Voriconazole pharmacokinetics and safety in immunocompromised children compared to adult patients", Antimicrob Agents Chemother, 54, pp.3225~3232 (2010)
- Shimizu T, "Bioinformatics research on inter-racial difference in drug metabolism I. Analysis on frequencies of mutant alleles and poor metabolizers on CYP2D6 and CYP2C19", Drug Metab Pharmacokinet, 18, pp.48~70 (2003)
- Solis-Munoz P, "Voriconazole hepatotoxicity in severe liver dysfunction", J Infect, 66, pp.80~86 (2013)
- 김민주, "Voriconazole 투여 중 발생한 환시 및 환청 1례", Infection and Chemotherapy, 43(5), pp.421~424 (2011), 대한감염학회
- Imhof A, "Neurological adverse events to voriconazole: evidence for therapeutic drug monitoring", Int J Infect Dis, 10, pp.S61~ (2006)
- den Hollander JG, "Incidence of voriconazole hepatotoxicity during intravenous and oral treatment for invasive fungal infections", J Antimicrob Chemother, 57, pp.1248~1250 (2006)
- Levin M-D, "Hepatotoxicity of oral and intravenous voriconazole in relation to cytochrome P450 polymorphisms", J Antimicrob Chemother, 60, pp.1104~1107 (2007)