Utility of Voriconazole Monitoring and Factors Affecting Its Levels in Patients Undergoing Hematopoietic Stem Cell Transplantation. Single Center Experience From India

• Published in: Blood 2012-11, Vol.120 (21), p.3035-3035
• Main Authors: Goyal, Gautam, Gota, Vikram, Patil, Pravin, Achuta, Dileep Kumar, Mathew, Libin, Bagal, Bhausaheb, Gawande, Jayant, Kannan, Sadhna, Khattry, Navin
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V120.21.3035.3035

Abstract 3035 Voriconazole (vori) is used for prophylaxis against fungal infections in BMT. Under and over-dosing of vori may influence the efficacy and safety of therapy, respectively. There is large variability in vori exposure following standard dose administration. Utility of Therapeutic Drug Monitoring (TDM) of vori in patients with invasive mycoses has been demonstrated and recommended that trough concentrations should be maintained between 1–5.5 μg/mL. Based on these observations we started TDM of vori in BMT patients at our centre to target trough plasma concentration of 1–6 μg/mL. Few reports are available on the TDM of vori in BMT. We report our experience. All patients (autologous-65, allogeneic-64) who received vori prophylaxis during peritransplant period between September 2008 and January 2012 were included. Vori prophylaxis was started atleast 3 days prior to start of conditioning regimen in all patients before April 2011. Since April 2011, patients undergoing autologous transplant received vori 1 day after completion of chemotherapy. All patients above 12 years received oral loading dose of 6 mg/kg (upto maximum of 400 mg) 12 hourly on first day followed by 4mg/kg as maintenance. Intravenous dosing was used if patients had severe mucositis or developed febrile neutropenia. Patients less than 12 years received 7mg/kg 12 hourly continuously. Vori levels were measured on 5th-7th day after start of loading dose. Subsequent levels were done 2– 4 weekly till discontinuation of drug. If first level was < 1 or > 6 μg/ml, each dose was increased or decreased by 50% respectively and levels repeated after a week. Vori was continued for at least 100 days for all patients undergoing allogeneic transplant and longer if patients were on steroids due to graft vs host disease. Autologous transplant patients received it for 28 days. Incidence of breakthrough fungal infection was recorded as definite (blood culture positivity or histological evidence), probable (CT scan evidence with positive fungal PCR or galactomannan positivity) or possible (CT evidence only). Demographic and laboratory factors affecting the levels evaluated were age, sex, height, weight, body surface area (BSA), liver and renal function parameters. Concomitant drugs being used were recorded for any effect on vori levels. Vori levels in plasma were determined by a validated HPLC assay. Paired samples were compared using t-test or Wilcoxin sign rank test. Influence of covariates on vori lev