Background Recipients of haematopoietic stem cells are at high risk of developing invasive fungal disease (IFD) which is the leading cause of morbidity and mortality in these immunocompromised patients.

Fluconazole and voriconazole are recommended as the first-line agents for IFD in the department of Haematology at the National Centre for Bone Marrow Transplants, Tunisia.

These two drugs are metabolised by cytochrome P450 (CYP) enzymes; they can also be inhibitors of these enzymes. Therefore, they are source of many drug interactions with drugs metabolised by these enzymes.

Purpose To analyse the drug interactions in hematopoietic stem cell transplant (HSCT) recipients receiving azole antifungal drugs (voriconazole and fluconazole) and investigate the impact of such interactions.

Materials and methods A retrospective study was performed on 1067 daily drug prescriptions of 38 patients (61% men and 39% women) treated with hematopoietic stem cells who were hospitalised during 2012 in the haematology and transplants service

Results The average number of drugs per prescription was 5 drugs, with a minimum of 3 and a maximum of 17.

The average number of interactions was 2 per prescription, ranging from 2 to 18 interactions.

60% of prescriptions collected contained an azole antifungal, with a slight predominance of voriconazole (34% vs. 26% for fluconazole).

74% of prescriptions containing an antifungal azole had at least one interaction with this antifungal drug.

In one patient, an association was noted contraindicated. This interaction involved the co-prescription of voriconazole and rifampicin (an enzyme inducer responsible for the decrease in the concentration of voriconazole in the blood of more than 95%).

Also a non-recommended interaction was observed in another patient between voriconazole and sirolimus.

The majority of interactions were classed as precautions for use (3rd level of risk):

Voriconazole: ciclosporin, nicardipine and sodium alginate

Fluconazole: ciclosporin, acenocoumarol and sodium alginate

We assessed the effects of azole antifungals administration on the concentration of calcineurin inhibitors, namely ciclosporin, in the recipients of hematopoietic stem cell transplants and revealed a notably wide inter-individual variability in the magnitude of the drug interaction.

Azoles, by their enzymatic inhibition of CYP3A4, increase plasma concentrations of ciclosporin and thus the risk of nephrotoxicity.

Conclusions Understanding the mechanisms of drug interactions allows clinicians to avoid certain interactions and to develop a possible strategy to minimise iatrogenic events. This is facilitated by the establishment of a computerised system in the service to prevent iatrogenic drug interactions and ensure patient safety.

References

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No conflict of interest.