Isavuconazole: Case Report and Pharmacokinetic Considerations

Francesco Marchesi, Corrado Girmenia, Bianca Maria Goffredo, Emanuela Salvatorelli, Atelda Romano, Andrea Mengarelli, Giorgio Minotti, Pierantonio Menna

Research output: Contribution to journalArticle

Abstract

Invasive fungal disease (IFD) is one of the major causes of morbidity and mortality in immunocompromised patients. Voriconazole (VCZ) and posaconazole (PCZ) remain the most widely used antifungals for the prophylaxis and treatment of IFD. However, VCZ and PCZ are liable for drug-drug interactions and show a pharmacokinetic variability that requires therapeutic drug monitoring (TDM). Isavuconazole (IVZ) is a newest generation triazole antifungal approved for the treatment of invasive aspergillosis (IA) in adult patients and for the treatment of invasive mucormycosis in adult patients for whom treatment with amphotericin B is inappropriate. In clinical trials, IVZ showed linear pharmacokinetics and little or no evidence for interactions with other drugs. There is only modest evidence on IVZ pharmacokinetics and TDM in real-life settings. Here, we report on IVZ pharmacokinetics in a young adult with Ph chromosome-negative acute lymphoblastic leukemia (ALL) who developed a "probable" IA during induction chemotherapy. The patient was initially treated with VCZ, but she developed a severe hepatic toxicity that was associated to the high plasma levels of VCZ. Therefore, VCZ was discontinued and the patient was switched to IVZ. After a loading dose of IVZ, the patient remained on IVZ for 5 months while also receiving standard maintenance chemotherapy for ALL. At day 65 after the start of IVZ, the patient experienced a significant hepatic toxicity; however, no change in IVZ plasma concentrations was observed in the face of a concomitant administration of many other drugs (cancer drugs, antiemetics, other anti-infectives). Hepatic toxicity resolved after discontinuing maintenance chemotherapy but not IVZ. These results show that (i) IVZ plasma concentrations remained stable throughout and were not affected by concomitant ALL therapy, and (ii) there was no relation between IVZ plasma concentration and hepatic toxicity. Thus, in clinical practice IVZ may not require TDM.

Original languageEnglish
Pages (from-to)253-256
Number of pages4
JournalChemotherapy
Volume63
Issue number5
DOIs
Publication statusE-pub ahead of print - Nov 20 2018

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Pharmacokinetics
Drug Monitoring
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Maintenance Chemotherapy
Aspergillosis
Mycoses
Liver
isavuconazole
Pharmaceutical Preparations
Mucormycosis
Therapeutics
Induction Chemotherapy
Triazoles
Antiemetics
Immunocompromised Host
Amphotericin B
Drug Interactions
Young Adult
Chromosomes
Voriconazole

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Isavuconazole : Case Report and Pharmacokinetic Considerations. / Marchesi, Francesco; Girmenia, Corrado; Goffredo, Bianca Maria; Salvatorelli, Emanuela; Romano, Atelda; Mengarelli, Andrea; Minotti, Giorgio; Menna, Pierantonio.

In: Chemotherapy, Vol. 63, No. 5, 20.11.2018, p. 253-256.

Research output: Contribution to journalArticle

Marchesi, Francesco ; Girmenia, Corrado ; Goffredo, Bianca Maria ; Salvatorelli, Emanuela ; Romano, Atelda ; Mengarelli, Andrea ; Minotti, Giorgio ; Menna, Pierantonio. / Isavuconazole : Case Report and Pharmacokinetic Considerations. In: Chemotherapy. 2018 ; Vol. 63, No. 5. pp. 253-256.
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AU - Minotti, Giorgio

AU - Menna, Pierantonio

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AB - Invasive fungal disease (IFD) is one of the major causes of morbidity and mortality in immunocompromised patients. Voriconazole (VCZ) and posaconazole (PCZ) remain the most widely used antifungals for the prophylaxis and treatment of IFD. However, VCZ and PCZ are liable for drug-drug interactions and show a pharmacokinetic variability that requires therapeutic drug monitoring (TDM). Isavuconazole (IVZ) is a newest generation triazole antifungal approved for the treatment of invasive aspergillosis (IA) in adult patients and for the treatment of invasive mucormycosis in adult patients for whom treatment with amphotericin B is inappropriate. In clinical trials, IVZ showed linear pharmacokinetics and little or no evidence for interactions with other drugs. There is only modest evidence on IVZ pharmacokinetics and TDM in real-life settings. Here, we report on IVZ pharmacokinetics in a young adult with Ph chromosome-negative acute lymphoblastic leukemia (ALL) who developed a "probable" IA during induction chemotherapy. The patient was initially treated with VCZ, but she developed a severe hepatic toxicity that was associated to the high plasma levels of VCZ. Therefore, VCZ was discontinued and the patient was switched to IVZ. After a loading dose of IVZ, the patient remained on IVZ for 5 months while also receiving standard maintenance chemotherapy for ALL. At day 65 after the start of IVZ, the patient experienced a significant hepatic toxicity; however, no change in IVZ plasma concentrations was observed in the face of a concomitant administration of many other drugs (cancer drugs, antiemetics, other anti-infectives). Hepatic toxicity resolved after discontinuing maintenance chemotherapy but not IVZ. These results show that (i) IVZ plasma concentrations remained stable throughout and were not affected by concomitant ALL therapy, and (ii) there was no relation between IVZ plasma concentration and hepatic toxicity. Thus, in clinical practice IVZ may not require TDM.

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