Efficacy and safety of Isavuconazole for the treatment of invasive <i>Aspergillus</i> infection - an update of the literature

Sivasubramanian, Geetha; Chandrasekar, Pranatharthi H.

doi:10.1080/14656566.2022.2032645

Cited by 6 publications

(5 citation statements)

References 73 publications

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“…A phase II single arm study probed isavuconazole, 29 a broad spectrum triazole that causes only mild–moderate inhibition of CYP3A4 30 and shows a good safety profile in terms of QTc prolongation and other AEs commonly associated with triazoles. 31 In the latter study, which also included patients with FLT3‐ mut AML, breakthrough IFIs were slightly more prevalent compared to historical cohorts of patients exposed to PCZ. 29 …”

Section: Discussionmentioning

confidence: 97%

“…We have shown that IFI incidence was similar in PCZ and micafungin groups, which in principle should reassure about the appropriateness of replacing PCZ with micafungin; however, absent robust studies in the settings of primary prophylaxis, these findings need to be considered with due caution. A phase II single arm study probed isavuconazole, 29 a broad spectrum triazole that causes only mild–moderate inhibition of CYP3A4 30 and shows a good safety profile in terms of QTc prolongation and other AEs commonly associated with triazoles 31 . In the latter study, which also included patients with FLT3‐ mut AML, breakthrough IFIs were slightly more prevalent compared to historical cohorts of patients exposed to PCZ 29 …”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Posaconazole and midostaurin in patients with FLT3‐mutated acute myeloid leukemia: Pharmacokinetic interactions and clinical facts in a real life study

Menna

Marchesi

Cattaneo

et al. 2023

Clinical Translational Sci

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Midostaurin is used in combination with chemotherapy to treat patients with newly diagnosed FLT3‐mutated acute myeloid leukemia. Chemotherapy‐induced neutropenia exposes these patients to a significant risk of invasive fungal infections (IFIs). International guidelines recommend primary antifungal prophylaxis with posaconazole (PCZ) but nested analysis of a phase III trial showed that strong PCZ inhibition of CYP3A4 diminished midostaurin metabolism and increased midostaurin plasma levels; however, midostaurin‐related adverse events (AEs) were only moderately exacerbated. We conducted a prospective multicenter real‐life study to evaluate (i) how often concerns around PCZ‐midostaurin interactions made the hematologist prescribe antifungals other than PCZ, (ii) how remarkably PCZ increased midostaurin plasma levels, and (iii) how significantly PCZ‐midostaurin interactions influenced hematologic and safety outcomes of induction therapy. Although the hematologists were blinded to pharmacokinetic findings, as many as 16 of 35 evaluable patients were prescribed antifungal prophylaxis with micafungin, weak CYP3A4 inhibitor, in place of PCZ (p < 0.001 for deviation from guidelines). In the 19 patients managed as per guidelines, PCZ‐midostaurin interactions were more remarkable than previously characterized, such that at the end of induction therapy midostaurin minimum plasma concentration (Cmin) was greater than three times higher than reported; moreover, midostaurin Cmin, maximum plasma concentration, and area under the curve were more than or equal to four times higher with PCZ than micafungin. Hematologic outcomes (complete remission and duration of severe neutropenia) and safety outcomes (midostaurin‐related any grade or grade ≥3 AEs) were nonetheless similar for patients exposed to PCZ or micafungin, as was the number of breakthrough IFIs. In waiting for randomized phase III trials of new prophylaxis regimens, these findings show that PCZ should remain the antifungal of choice for the midostaurin‐treated patient.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Posaconazole and midostaurin in patients with FLT3‐mutated acute myeloid leukemia: Pharmacokinetic interactions and clinical facts in a real life study

Menna

Marchesi

Cattaneo

et al. 2023

Clinical Translational Sci

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“…As to our experience, once suspicion of AIFRS was raised according to clinical manifestation, antifungal treatment should be initiated as soon as possible, usually Voriconazole for Aspergillus and amphotericin B for Mucor. In recent years, FDA has approved isavuconazole, which was effective against Aspergillus and some Mucor, and it was water-soluble, with less impact on renal function and hepatic function than amphotericin B [7,8].…”

Section: Antifungal Agent Was Important To Aifrs Patientsmentioning

confidence: 99%

Management of acute invasive fungal rhinosinusitis with orbit-cranio-facial involved------ our experience with 8 cases

Yang

Shen

Wang

et al. 2023

Preprint

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Key points:  Diagnosis of AIFRS should be alert in the immunocompromised patient presenting with new-onset, rapidly progressive sinusitis with facial-cranio-orbital spread.  Extended debridement should be considered on a case-by-case basis.  Antifungal agent contributed greatly to the outcome of AIFRS.  Prognosis mostly up to the balance of underlying disease and fungal invasion, more emphasizes should be focused on comprehensive treatment.  AIFRS with facial-cranio-orbital involved often had a disastrous end.

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“…Triazole antifungals cease fungal growth by inhibiting lanolin 1-4-alpha-demethylase, the cytochrome P450-dependent membrane protein that inhibits the conversion of lanolin to ergosterol, which is primarily responsible for maintaining the integrity of fungal cell membrane. 1 – 3 Triazole antifungals are broad-spectrum antifungals with clinical indications such as the prevention and treatment of invasive fungal diseases primarily caused by immune deficiency, including the prevention and treatment of invasive fungal diseases caused primarily by immune deficiency. 2 , 4 For the therapy of candidemia in nonneutropenic, invasive pulmonary aspergillosis (IPA), and to prevent invasive candidiasis in the intensive care unit setting, the preferred administration of triazole antifungals as therapeutic agents was proposed by the Clinical Practice Guideline for the Management of Candidiasis and Practice Guidelines for the Diagnosis and Management of Aspergillosis of the Infectious Diseases Society of America (IDSA), updated in 2016.…”

Section: Introductionmentioning

confidence: 99%

Safety of triazole antifungals: a pharmacovigilance study from 2004 to 2021 based on FAERS

Chai

Zhan

Zhao

et al. 2022

Therapeutic Advances in Drug Safety

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Background: Triazole antifungals are widely used as broad-spectrum antifungal activity; however, there are many undetected and unreported adverse events (AEs). Methods: Data from the Food and Drug Administration Adverse Event Reporting System (FAERS) from the first quarter (Q1) of 2004 to the third quarter (Q3) of 2021 were selected for disproportionality analysis to assess the connection between antifungal triazoles, and AEs and important medical events (IMEs). Results: A total of 22,566 records associated with triazole antifungals were identified, with 9584 triazole antifungal–IME pairs. The following system organ classes (SOCs) appeared as significant signals: ‘Endocrine disorders’ [reported odds ratio (ROR) = 167.94], ‘Metabolism and nutrition disorders’ (ROR = 46.30), and ‘Skin and subcutaneous tissue disorders’ (ROR = 21.37). Strong signals were observed with respiratory failure, rash, hepatic function abnormal, and hypokalemia. Uncommon security signals included a change in the QT interval, neurotoxicity, pseudoaldosteronism, and hallucinations. Conclusion: Various triazole antifungals cause AEs of different types and intensities of association. Our results are broadly consistent with prescribing information and previous studies; however, additional pharmacoepidemiological studies are required to verify AEs with modest incidence but high signal. Plain Language Summary A study on the adverse effects of triazole antifungals Introduction: The triazole antifungals we studied include fluconazole, itraconazole, voriconazole, posaconazole, and isavuconazole. Triazole antifungals are widely used as broad-spectrum antifungals; however, there are many undetected and unreported adverse events (AEs). Materials and Methods: The Food and Drug Administration Adverse Event Reporting System (FAERS) database contains AEs reported to the FDA by different countries regarding post-marketing drugs. Through the FAERS database, we retrieved a total of 22,566 AE reports related to triazole antifungals. We not only counted information about patients’ gender, age, weight, reporting country, outcome indicators, and indications but also analyzed the system organ classes (SOCs) of AEs, and the number of reported drug-related AEs and the degree of relevance. Results: We found a total of 22,566 records related to triazole antifungal agents, of which 9584 reports made important medical events (IMEs) about triazole antifungal agents, which are serious AEs. The following SOCs appear as important signals: ‘endocrine disorders’, ‘metabolic and nutritional disorders’, and ‘skin and subcutaneous tissue disorders’. Triazole antifungals produce AEs, such as respiratory failure, rash, hepatic function abnormal, and hypokalemia. They also produce uncommon AEs, including changes in the QT interval, neurotoxicity, pseudoaldosteronism, and hallucinations. Conclusion: By analyzing data from the FAERS database, we identified more AEs associated with these five triazole antifungals than were indicated in the instructions and our findings provide additional insight into triazole-related AEs to inform clinicians before and during treatment.

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Efficacy and safety of Isavuconazole for the treatment of invasive Aspergillus infection - an update of the literature

Cited by 6 publications

References 73 publications

Posaconazole and midostaurin in patients with FLT3‐mutated acute myeloid leukemia: Pharmacokinetic interactions and clinical facts in a real life study

Posaconazole and midostaurin in patients with FLT3‐mutated acute myeloid leukemia: Pharmacokinetic interactions and clinical facts in a real life study

Management of acute invasive fungal rhinosinusitis with orbit-cranio-facial involved------ our experience with 8 cases

Safety of triazole antifungals: a pharmacovigilance study from 2004 to 2021 based on FAERS

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