An update on the safety and interactions of antifungal drugs in stem cell transplant recipients

ABSTRACT

Introduction: Invasive fungal diseases (IFDs) are a major cause of morbidity and mortality in patients undergoing allogeneic hematopoietic stem cell transplant (HSCT). Improvement in the management of IFDs have been achieved with the availability of new effective and safe antifungal drugs, however, many of these newer treatments have some limitations in their variable toxicity and unique predisposition for pharmacokinetic drug-drug interactions.

Areas covered: This article is an update of a previous review published in this journal evaluating the safety profile of the antifungal drugs. Interesting new features include the availability of the new drug isavuconazole and the new tablet and intravenous formulations of posaconazole. Different dosages and new ways of administration of liposomal Amphotericin B (L-AmB) and echinocandins may be considered in the HSCT practice.

Expert opinion: Nephrotoxicity continues to be a clinically relevant and frequent side effect of L-AmB which may cause a reduced clearance of other renally eliminated drugs frequently used in HSCT patients. Echinocandins are favorable therapeutic options in view of their low toxicity and uncommon drug-drug interactions. Important limitations of triazoles are represented by hepatic toxicity and certain side effects particularly after prolonged treatments. The new triazole isavuconazole and the new tablet formulation of posaconazole will be probably increasingly used in the HSCT setting not only due to their efficacy but in particular for their interesting toxicity profile and pharmacokinetic characteristics. The knowledge of these pharmacological findings is crucial in the daily care of allogeneic HSCT patients.

KEYWORDS:

• Antifungals
• toxicity
• interactions
• allogeneic HSCT

Article highlights

• The knowledge of pharmacokinetic and toxicity profile of antifungal agents and their possible interaction with other drugs in allogeneic HSCT patients is crucial in the daily clinical practice.

• The co-administration of certain antifungals may interfere with several drugs commonly used in allogeneic HSCT patients including cytotoxic drugs used in the pretransplant conditioning regimen and immunosuppressive agents used for the prevention and treatment of Graft Versus Host Disease. Unfortunately, the knowledge of drug-drug interactions is less than ideal in the real life.

• Thank to the favourable toxicity and drug-drug interaction profile echinocandins continue to be particularly suitable for the allogeneic HSCT setting.

• The use of Lipid formulations of AmB in the HSCT setting may be associated to some reversible side effects and additive toxicity with other nephrotoxic drugs.

• The triazoles, in particular voriconazole, are characterized by important drug-drug interactions and serum level monitoring of triazoles and of the interacting drugs is usually required. The new tablet formulation of posaconazole is characterized by a significantly improved bioavailability compared to the oral suspension formulation.

• The new triazole isavuconazole is characterized by very low toxicity and propensity to interactions. It is an interesting alternatives to voriconazole and L-AmB in the tratement of aspergillosis and mucormycosis, respectively, but more real life data in the HSCT setting are required.

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Declaration of interest

C Gimenia has received payment for lectures through speaker’s bureaus for Gilead, Pfizer, Astellas, MSD and Basilea. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This paper was not funded.