{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T21:32:48Z","timestamp":1768253568708,"version":"3.49.0"},"reference-count":20,"publisher":"The Pediatric Pharmacy Association","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021]]},"abstract":"Prolonged neutropenia increases the risk for lethal invasive fungal infections (IFIs) such as those caused by Rhizopus<\/jats:italic> species. Isavuconazonium sulfate is a new triazole that lacks pediatric dosing recommendations. Clinical courses of 4 pediatric patients with IFIs in the peri-allogeneic hematopoietic cell transplantation (alloHCT) period between 2015 and 2017 were reviewed. The reviews included previously unreported pharmacokinetic and safety data, and the IFIs included Rhizopus<\/jats:italic>. Isavuconazonium sulfate was initiated with a loading dose followed by daily dosing, adjusted to a goal trough concentration of >3 mg\/L based on adult literature. This target was achieved at a median of 7 days, demonstrating varying rates of metabolism. Renal insufficiency, electrolyte disturbances, and transaminitis were noted, although attribution was confounded by other alloHCT complications. One patient survived infection-free to hospital discharge and 1 of 3 deceased patients had evidence of an unresolved IFI (case 2). Case 2 was subtherapeutic for 39% of the duration of treatment, compared with others at an average of 29%, suggesting this target trough to be clinically relevant because case 2 demonstrated positive sinus and nasal cultures for Rhizopus<\/jats:italic> on autopsy. We recommend initiation of isavuconazonium 10 mg\/kg with a maximum dose of 372 mg. A loading dose of 10 mg\/kg is used every 8 hours for 6 doses followed by 10 mg\/kg dosing every 24 hours. Monitoring must continue beyond steady state. If early monitoring is not possible, we recommend a first drug level at week 3. If dose increases are required, a partial reload has been more successful instead of increasing daily doses. Further larger studies are needed to demonstrate optimum dosing in pediatric patients.<\/jats:p>","DOI":"10.5863\/1551-6776-26.8.863","type":"journal-article","created":{"date-parts":[[2021,11,11]],"date-time":"2021-11-11T00:52:57Z","timestamp":1636591977000},"page":"863-867","source":"Crossref","is-referenced-by-count":2,"title":["Isavuconazonium Sulfate Use in Multi-Modal Management of Invasive Mucormycosis in Four Pediatric Allogeneic Hematopoietic Cell Transplant Patients"],"prefix":"10.5863","volume":"26","author":[{"given":"Asmaa","family":"Ferdjallah","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristina M.","family":"Nelson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kailey","family":"Meyer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cathryn A.","family":"Jennissen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christen L.","family":"Ebens","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"3883","reference":[{"issue":"7","key":"i1551-6776-26-8-863-b1","series-title":"Lancet Infect Dis","first-page":"828","article-title":"Isavuconazole treatment for mucormycosis: a single-arm open-label trial and case-control analysis","volume":"16","year":"2016","unstructured":"Marty\n FM,\n \n \n Ostrosky-Zeichner\n L,\n \n \n Cornely\n OA,\n \n \n .\n\t\t\t\t\tIsavuconazole treatment for mucormycosis: a single-arm open-label trial and case-control analysis.\n\t\t\t\t\tLancet Infect Dis.\n\t\t\t\t\t2016;\n\t\t\t\t\t16(\n\t\t\t\t\t7):\n\t\t\t\t\t828\u2013\n\t\t\t\t\t837."},{"issue":"5","key":"i1551-6776-26-8-863-b2","series-title":"Clin Infect Dis","first-page":"634","article-title":"Epidemiology and outcome of zygomycosis: a review of 929 reported cases","volume":"41","year":"2005","unstructured":"Roden\n MM,\n \n \n Zaoutis\n TE,\n \n \n Buchanan\n WL,\n \n \n .\n\t\t\t\t\tEpidemiology and outcome of zygomycosis: a review of 929 reported cases.\n\t\t\t\t\tClin Infect Dis.\n\t\t\t\t\t2005;\n\t\t\t\t\t41(\n\t\t\t\t\t5):\n\t\t\t\t\t634\u2013\n\t\t\t\t\t653."},{"issue":"7","key":"i1551-6776-26-8-863-b3","series-title":"Clin Infect Dis","first-page":"909","article-title":"Epidemiology and outcome of mould infections in hematopoietic stem cell transplant recipients","volume":"34","year":"2002","unstructured":"Marr\n KA,\n \n \n Carter\n RA,\n \n \n Crippa\n F,\n \n \n .\n\t\t\t\t\tEpidemiology and outcome of mould infections in hematopoietic stem cell transplant recipients.\n\t\t\t\t\tClin Infect Dis.\n\t\t\t\t\t2002;\n\t\t\t\t\t34(\n\t\t\t\t\t7):\n\t\t\t\t\t909\u2013\n\t\t\t\t\t917."},{"issue":"2","key":"i1551-6776-26-8-863-b4","series-title":"Mycoses","first-page":"165","article-title":"Invasive mucormycosis in children with cancer: a retrospective study from the Infection Working Group of Italian Pediatric Hematology Oncology Association","volume":"62","year":"2019","unstructured":"Muggeo\n P,\n \n \n Calore\n E,\n \n \n Decembrino\n N,\n \n \n .\n\t\t\t\t\tInvasive mucormycosis in children with cancer: a retrospective study from the Infection Working Group of Italian Pediatric Hematology Oncology Association.\n\t\t\t\t\tMycoses.\n\t\t\t\t\t2019;\n\t\t\t\t\t62(\n\t\t\t\t\t2):\n\t\t\t\t\t165\u2013\n\t\t\t\t\t170."},{"issue":"4","key":"i1551-6776-26-8-863-b5","series-title":"Clin Infect Dis","first-page":"503","article-title":"Delaying amphotericin B-based frontline therapy significantly increases mortality among patients with hematologic malignancy who have zygomycosis","volume":"47","year":"2008","unstructured":"Chamilos\n G,\n \n \n Lewis\n RE,\n \n \n Kontoyiannis\n DP.\n \n \n Delaying amphotericin B-based frontline therapy significantly increases mortality among patients with 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\n \n Malecka\n A,\n \n \n Jaworski\n R,\n \n \n .\n\t\t\t\t\tIsavuconazole in a successful combination treatment of disseminated mucormycosis in a child with acute lymphoblastic leukaemia and generalized haemochromatosis: a case report and review of the literature.\n\t\t\t\t\tMycopathologia.\n\t\t\t\t\t2019;\n\t\t\t\t\t184(\n\t\t\t\t\t1):\n\t\t\t\t\t81\u2013\n\t\t\t\t\t88."},{"issue":"3","key":"i1551-6776-26-8-863-b8","series-title":"Antimicrob Agents Chemother","first-page":"1671","article-title":"A phase 2, randomized, double-blind, multicenter trial to evaluate the safety and efficacy of three dosing regimens of isavuconazole compared with fluconazole in patients with uncomplicated esophageal candidiasis","volume":"59","year":"2015","unstructured":"Viljoen\n J,\n \n \n Azie\n N,\n \n \n Schmitt-Hoffmann\n AH,\n \n \n Ghannoum\n M.\n \n \n A phase 2, randomized, double-blind, multicenter trial to evaluate the safety and efficacy of three dosing regimens of isavuconazole compared with fluconazole in patients with uncomplicated esophageal candidiasis.\n\t\t\t\t\tAntimicrob Agents Chemother.\n\t\t\t\t\t2015;\n\t\t\t\t\t59(\n\t\t\t\t\t3):\n\t\t\t\t\t1671\u2013\n\t\t\t\t\t1679."},{"issue":"10020","key":"i1551-6776-26-8-863-b9","series-title":"Lancet","first-page":"760","article-title":"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","volume":"387","year":"2016","unstructured":"Maertens\n JA,\n \n \n Raad\n II,\n \n \n Marr\n KA,\n \n \n .\n\t\t\t\t\tIsavuconazole 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.\n\t\t\t\t\tLancet.\n\t\t\t\t\t2016;\n\t\t\t\t\t387(\n\t\t\t\t\t10020):\n\t\t\t\t\t760\u2013\n\t\t\t\t\t769."},{"issue":"3","key":"i1551-6776-26-8-863-b10","series-title":"Clin Infect Dis","first-page":"324","article-title":"Epidemiology and outcome of fungemia in a cancer cohort of the Infectious Diseases Group (IDG) of the European Organization for Research and Treatment of Cancer (EORTC 65031)","volume":"61","year":"2015","unstructured":"Cornely\n OA,\n \n \n Gachot\n B,\n \n \n Akan\n H,\n \n \n .\n\t\t\t\t\tEpidemiology and outcome of fungemia in a cancer cohort of the Infectious Diseases Group (IDG) of the European Organization for Research and Treatment of Cancer (EORTC 65031).\n\t\t\t\t\tClin Infect Dis.\n\t\t\t\t\t2015;\n\t\t\t\t\t61(\n\t\t\t\t\t3):\n\t\t\t\t\t324\u2013\n\t\t\t\t\t331."},{"issue":"10","key":"i1551-6776-26-8-863-b11","series-title":"Pediatr Blood Cancer","first-page":"e27281","article-title":"Successful treatment of invasive mucormycosis with isavuconazole in pediatric patients","volume":"65","year":"2018","unstructured":"Barg\n AA,\n \n \n Malkiel\n S,\n \n \n Bartuv\n M,\n \n \n .\n\t\t\t\t\tSuccessful treatment of invasive mucormycosis with isavuconazole in pediatric patients.\n\t\t\t\t\tPediatr Blood Cancer.\n\t\t\t\t\t2018;\n\t\t\t\t\t65(\n\t\t\t\t\t10):\n\t\t\t\t\te27281."},{"issue":"1","key":"i1551-6776-26-8-863-b12","series-title":"BMC Pharmacol Toxicol","first-page":"81","article-title":"Successful outcome of disseminated mucormycosis in a 3-year-old child suffering from acute leukaemia: the role of isavuconazole? A case report","volume":"19","year":"2018","unstructured":"Cornu\n M,\n \n \n Bruno\n B,\n \n \n Loridant\n S,\n \n \n .\n\t\t\t\t\tSuccessful outcome of disseminated mucormycosis in a 3-year-old child suffering from acute leukaemia: the role of isavuconazole? A case report.\n\t\t\t\t\tBMC Pharmacol Toxicol.\n\t\t\t\t\t2018;\n\t\t\t\t\t19(\n\t\t\t\t\t1):\n\t\t\t\t\t81."},{"issue":"6","key":"i1551-6776-26-8-863-b13","series-title":"J Pediatr Hematol Oncol","first-page":"e469","article-title":"Isavuconazole treatment of cerebral and pulmonary aspergillosis in a pediatric patient with acute lymphoblastic leukemia: case report and review of literature","volume":"42","year":"2020","unstructured":"De Leonardis\n F,\n \n \n Novielli\n C,\n \n \n Giannico\n B,\n \n \n .\n\t\t\t\t\tIsavuconazole treatment of cerebral and pulmonary aspergillosis in a pediatric patient with acute lymphoblastic leukemia: case report and review of literature.\n\t\t\t\t\tJ Pediatr Hematol Oncol.\n\t\t\t\t\t2020;\n\t\t\t\t\t42(\n\t\t\t\t\t6):\n\t\t\t\t\te469\u2013\n\t\t\t\t\te471."},{"issue":"10","key":"i1551-6776-26-8-863-b14","series-title":"Pediatr Infect Dis J","first-page":"1035","article-title":"Isavuconazole-induced acute liver failure in a pediatric patient with invasive aspergillosis","volume":"38","year":"2019","unstructured":"Brivio\n E,\n \n \n Verna\n M,\n \n \n Migliorino\n GM,\n \n \n .\n\t\t\t\t\tIsavuconazole-induced acute liver failure in a pediatric patient with invasive aspergillosis.\n\t\t\t\t\tPediatr Infect Dis J.\n\t\t\t\t\t2019;\n\t\t\t\t\t38(\n\t\t\t\t\t10):\n\t\t\t\t\t1035\u2013\n\t\t\t\t\t1037."},{"issue":"7\u20138","key":"i1551-6776-26-8-863-b15","series-title":"Ann Pharmacother","first-page":"976","article-title":"Posaconazole therapeutic drug monitoring in pediatric patients and young adults with cancer","volume":"47","year":"2013","unstructured":"Bernardo\n VA,\n \n \n Cross\n SJ,\n \n \n Crews\n KR,\n \n \n .\n\t\t\t\t\tPosaconazole therapeutic drug monitoring in pediatric patients and young adults with cancer.\n\t\t\t\t\tAnn Pharmacother.\n\t\t\t\t\t2013;\n\t\t\t\t\t47(\n\t\t\t\t\t7\u20138):\n\t\t\t\t\t976\u2013\n\t\t\t\t\t983."},{"issue":"6\u20138","key":"i1551-6776-26-8-863-b16","series-title":"J Chemother","first-page":"380","article-title":"Acute kidney injury: an unusual complication of posaconazole use","volume":"30","year":"2018","unstructured":"Otu\n A,\n \n \n Bongomin\n F,\n \n \n Kosmidis\n C,\n \n \n Denning\n DW.\n \n \n Acute kidney injury: an unusual complication of posaconazole use.\n\t\t\t\t\tJ Chemother.\n\t\t\t\t\t2018;\n\t\t\t\t\t30(\n\t\t\t\t\t6\u20138):\n\t\t\t\t\t380\u2013\n\t\t\t\t\t383."},{"issue":"7","key":"i1551-6776-26-8-863-b17","series-title":"Antimicrob Agents Chemother","first-page":"e00585","article-title":"Isavuconazole concentration in real-world practice: consistency with results from clinical trials","volume":"62","year":"2018","unstructured":"Andes\n D,\n \n \n Kovanda\n L,\n \n \n Desai\n A,\n \n \n .\n\t\t\t\t\tIsavuconazole concentration in real-world practice: consistency with results from clinical trials.\n\t\t\t\t\tAntimicrob Agents Chemother.\n\t\t\t\t\t2018;\n\t\t\t\t\t62(\n\t\t\t\t\t7):\n\t\t\t\t\te00585\u2013\n\t\t\t\t\t18."},{"issue":"3","key":"i1551-6776-26-8-863-b18","series-title":"Antimicrob Agents Chemother","first-page":"e01783","article-title":"A case series and literature review of isavuconazole use in pediatric patients with hemato-oncologic diseases and hematopoietic stem cell transplantation","volume":"64","year":"2020","unstructured":"Decembrino\n N,\n \n \n Perruccio\n K,\n \n \n Zecca\n M,\n \n \n .\n\t\t\t\t\tA case series and literature review of isavuconazole use in pediatric patients with hemato-oncologic diseases and hematopoietic stem cell transplantation.\n\t\t\t\t\tAntimicrob Agents Chemother.\n\t\t\t\t\t2020;\n\t\t\t\t\t64(\n\t\t\t\t\t3):\n\t\t\t\t\te01783\u2013\n\t\t\t\t\t19."},{"issue":"3","key":"i1551-6776-26-8-863-b19","series-title":"J Antimicrob Chemother","first-page":"761","article-title":"Variability and exposure-response relationships of isavuconazole plasma concentrations in the phase 3 SECURE trial of patients with invasive mould diseases","volume":"74","year":"2019","unstructured":"Kaindl\n T,\n \n \n Andes\n D,\n \n \n Engelhardt\n M,\n \n \n .\n\t\t\t\t\tVariability and exposure-response relationships of isavuconazole plasma concentrations in the phase 3 SECURE trial of patients with invasive mould diseases.\n\t\t\t\t\tJ Antimicrob Chemother.\n\t\t\t\t\t2019;\n\t\t\t\t\t74(\n\t\t\t\t\t3):\n\t\t\t\t\t761\u2013\n\t\t\t\t\t767."},{"issue":"8","key":"i1551-6776-26-8-863-b20","series-title":"J Antimicrob Chemother","first-page":"2341","article-title":"Serial monitoring of isavuconazole blood levels during prolonged antifungal therapy","volume":"74","year":"2019","unstructured":"Furfaro\n E,\n \n \n Signori\n A,\n \n \n Di Grazia\n C,\n \n \n .\n\t\t\t\t\tSerial monitoring of isavuconazole blood levels during prolonged antifungal therapy.\n\t\t\t\t\tJ Antimicrob Chemother.\n\t\t\t\t\t2019;\n\t\t\t\t\t74(\n\t\t\t\t\t8):\n\t\t\t\t\t2341\u2013\n\t\t\t\t\t2346."}],"container-title":["The Journal of Pediatric Pharmacology and 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