Therapeutic Drug Monitoring of Isavuconazole: Lessons Learnt from a Real-life Setting in a Tertiary Care Center in India
Shweta P Panchakshari, Preeti S Ajapuje, Namita P Mahale, Sadanand S Naik, Sharwari Narawade, Anand Athavale
Keywords :
Aspergillosis, Drug monitoring, Fungal infections, Fungus, Isavuconazole, Mold infections, Mucormycosis, Therapeutic drug monitoring
Citation Information :
Panchakshari SP, Ajapuje PS, Mahale NP, Naik SS, Narawade S, Athavale A. Therapeutic Drug Monitoring of Isavuconazole: Lessons Learnt from a Real-life Setting in a Tertiary Care Center in India. Indian J Crit Care Med 2023; 27 (4):260-264.
Introduction: Isavuconazole is an emerging therapeutic option for invasive infections caused by molds, especially aspergillosis and mucormycosis. Isavuconazole has predictable pharmacokinetics and good bioavailability. These attributes have led to some doubts regarding the need for therapeutic drug monitoring (TDM). There are no data from India regarding TDM for isavuconazole.
Methods: A retrospective analysis of 50 patients who received oral isavuconazole for therapeutic purposes. Plasma isavuconazole levels were measured using a reversed phase high-performance liquid chromatography (HPLC) and UV detector with acetonitrile (ACN) as protein precipitating solvent.
Results: Of the 50 cases, 5 (10.0%) patients had subtherapeutic levels, while 45 (90.0%) had therapeutic levels. Higher body weight and solid organ transplantation (SOT) were significantly associated with subtherapeutic levels of isavuconazole (p-value < 0.05 for all). Receipt of a SOT was the only independent and statistically significant factor which was associated with subtherapeutic levels of isavuconazole (p-value < 0.05).
Conclusion: Our study reemphasizes the need of TDM for isavuconazole and adds to the growing evidence for the need to obtain drug levels. Factors associated with subtherapeutic levels of isavuconazole need to be assessed in larger studies to help identify those patients who are at risk of having subtherapeutic drug levels.
Cornely OA, Alastruey-Izquierdo A, Arenz D, Chen SC, Dannaoui E, Hochhegger B, et al. Global guideline for the diagnosis and management of mucormycosis: An initiative of the European Confederation of Medical Mycology in cooperation with the Mycoses Study Group Education and Research Consortium. Lancet Infect Dis 2019;19(12):e405–e421. DOI: 10.1016/S1473-3099(19)30312-3.
Maertens JA, Raad II, Marr KA, Patterson TF, Kontoyiannis DP, Cornely OA, et al. Isavuconazole versus voriconazole for primary treatment of invasive mould disease caused by Aspergillus and other filamentous fungi (SECURE): A phase 3, randomised-controlled, non-inferiority trial. Lancet 2016;387(10020):760–769. DOI: 10.1016/S0140-6736(15)01159-9.
McCarthy MW, Moriyama B, Petraitiene R, Walsh TJ, Petraitis V. Clinical pharmacokinetics and pharmacodynamics of isavuconazole. Clin Pharmacokinet 2018;57(12):1483–1491. DOI: 10.1007/s40262-018-0673-2.
Patterson TF, Thompson III GR, Denning DW, Fishman JA, Hadley S, Herbrecht R, et al. Practice guidelines for the diagnosis and management of aspergillosis: 2016 update by the infectious diseases society of America. Clin Infect Dis 2016;63(4):e1–e60. DOI: 10.1093/cid/ciw326.
Andes D, Kovanda L, Desai A, Kitt T, Zhao M, Walsh TJ. Isavuconazole concentration in real-world practice: Consistency with results from clinical trials. Antimicrob Agents Chemother 2018;62(7): e00585–e005818. DOI: 10.1128/AAC.00585-18.
Furfaro E, Signori A, Di Grazia C, Dominietto A, Raiola AM, Aquino S, et al. Serial monitoring of isavuconazole blood levels during prolonged antifungal therapy. J Antimicrob Chemother 2019;74(8):2341–2346. DOI: 10.1093/jac/dkz188.
Bruns AH, Roukens AH, Baas IO, van Steeg K, Toren-Wielema ML, Tersmette M, et al. The Dutch Working Party on Antibiotic Policy (SWAB) recommendations for the diagnosis and management of febrile neutropenia in patients with cancer. Infect Dis Ther 2022;11(6):2063–2098. DOI: 10.1007/s40121-022-00700-1.
Seyedmousavi S, Brüggemann RJ, Meis JF, Melchers WJ, Verweij PE, Mouton JW. Pharmacodynamics of isavuconazole in an Aspergillus fumigatus mouse infection model. Antimicrob Agents Chemother 2015;59(5):2855–2866. DOI: 10.1128/AAC.04907-14.
Buil JB, Brüggemann RJ, Wasmann RE, Zoll J, Meis JF, Melchers WJ, et al. Isavuconazole susceptibility of clinical Aspergillus fumigatus isolates and feasibility of isavuconazole dose escalation to treat isolates with elevated MICs. J Antimicrob Chemother 2018;73(1):134–142. DOI: 10.1093/jac/dkx354.
Kosmidis C, Otu A, Moore CB, Richardson MD, Rautemaa-Richardson R. Isavuconazole therapeutic drug monitoring during long-term treatment for chronic pulmonary aspergillosis. Antimicrob Agents Chemother 2020;65(1):e01511–e01520. DOI: 10.1128/AAC.01511-20.