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Arzneimittel-Interaktionen mit systemischen Antimykotika beim Intensivpatienten

Drug interactions with systemic antimycotics in intensive care patients

  • KLINISCHE PRAXIS
  • Published:
Intensivmedizin und Notfallmedizin

Abstract

Invasive mycoses are a frequent problem in the treatment of intensive care patients. Available antimycotic drugs for treatment are antimycotics of the polyene group (Amphotericin B, liposomal Amphotericin B), Azole-antimycotics (Fluconazole, Itraconazole, Voriconazole, Posaconazole), Caspofungin as a member of the echinocandin group and the antimetabolite flucytosine. As intensive care patients additionally receive further drugs, potential drug-drug interactions have to be considered. All available systemic antimycotics could potentially be involved in interactions. These drug-drug interactions could either result in a change of efficacy of the other drugs by the antimycotic or vice versa in a change of the antimycotic efficacy by the other drugs. Pharmacodynamic interactions, e.g. additive nephro- or myelotoxicity, are typical for the polyene antimycotics and flucytosine. Pharmacokinetic interactions with an inhibition of cytochrome P450 mediated metabolism are characteristic for the azole antimycotic group. An induction of the metabolism of intraconazole, voriconazole and caspofungin by the well-known cytochrome P450 enzyme inducers (e.g. rifampin, phenytoin, phenobarbital, carbamazepine) could result in a loss of antimycotic efficacy if the dose of these antimycotic agents is not increased. Within the multitude of drug interactions thinkable, those that are clinically relevant are summarized and categorized according to their position and consequences in intensive care.

Zusammenfassung

Invasive Mykosen stellen ein häufiges Problem in der Behandlung von Intensivpatienten dar. Zur Behandlung stehen Antimykotika aus der Gruppe der Polyene (Amphotericin B, liposomales Amphotericin B), der Azole (Fluconazol, Itraconazol, Voriconazol, Posaconazol) sowie als Vertreter der Echinocandine Caspofungin und als Antimetabolit Flucytosin zur Verfügung. Darüber hinaus erhalten Intensivpatienten in der Regel weitere Arzneimittel, so dass potentielle Arzneimittelinteraktionen zu beachten sind, bei denen entweder das Antimykotikum die Wirksamkeit des anderen Arzneimittels verändert oder umgekehrt die Effektivität des Antimykotikums durch das andere Arzneimittel verändert werden kann. Alle derzeit verfügbaren systemischen Antimykotika können potentiell in Interaktionen involviert sein. Pharmakodynamische Interaktionen z.B. durch additive Nephro- oder Hämatotoxizität betreffen insbesondere die Polyene und Flucytosin. Pharmakokinetische Interaktionen durch Hemmung der Metabolisierung durch Cytochrom P450-Isoenzyme sind charakteristisch für die Azol-Antimykotika. Eine Aktivierung der Metabolisierung von Itraconazol, Voriconazol und Caspofungin durch klassische Enzyminduktoren (z. B. Rifampicin, Phenytoin, Phenobarbital, Carbamazepin) kann ohne eine Dosiserhöhung zu einem antimykotischen Wirkverlust führen. Aus der Vielzahl denkbarer Interaktionen werden die klinisch relevanten zusammengefasst und hinsichtlich der Konsequenzen und des Stellenwerts im Rahmen der Intensivtherapie gegliedert.

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Authors and Affiliations

  1. Institut für Klinische Pharmakologie, Universität Rostock, Schillingallee 70, 18057, Rostock, Germany

    Silke C. Müller

  2. Abteilung Pneumologie, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, 30625, Hannover, Germany

    Tobias Welte

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  2. Tobias Welte
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Correspondence to Silke C. Müller.

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Müller, S.C., Welte, T. Arzneimittel-Interaktionen mit systemischen Antimykotika beim Intensivpatienten. Intensivmed 44, 526–534 (2007). https://doi.org/10.1007/s00390-007-0828-0

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  • DOI: https://doi.org/10.1007/s00390-007-0828-0

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