Background Triazole antifungals (itraconazole and voriconazole), are commonly used for treating isolates of Aspergillus, or in combination with corticosteroids for the empiric treatment of Allergic Bronchopulmonary Aspergillosis (ABPA) in children with cystic fibrosis (CF). Posaconazole is a newer triazole that is as effective, but better tolerated than voriconazole and itraconazole in immunocompromised patients¹ though there is no published use in CF and it is not licensed in children<18 years old. It is used as a 3rd line agent for Aspergillus or ABPA in our institution.

Aim Our aim was to evaluate why posaconazole was needed in some children, and to assess its tolerability. Given the difficulty in reaching therapeutic drug levels of triazoles in children with CF² we also reviewed posaconazole blood levels.

Method A retrospective case note review of all children with CF who had received voriconazole or posaconazole from April 2014 to May 2015 in a tertiary paediatric CF centre with a clinic population of 350 children. Children were identified from pharmacy records and clinical data was collected from case notes and computerised laboratory records. We compared reported adverse effects for both drugs, and for the posaconazole group documented reason for use and blood levels (therapeutic >0.7 mg/L).

Results Voriconazole was used in 10 children with a median age of 13.5 years (range 12–16), for median 8 weeks. Adverse effects were experienced in 5/10 (50%) of children (photosensitivity – 4; hallucinations and nausea – 1), and 2 children had raised liver functions tests (LFTs). Posaconazole was used in 7 children with a median age of 14 years (range 13–16) for median 37 weeks. No adverse effects were reported but LFTs were raised in 1 child. Posaconazole was commenced in 6/7 (85%) children due to severe photosensitivity with voriconazole. Of these, posaconazole was indicated for concurrent Scedosporium isolates in 2 children, and therapeutic failure with itraconazole in 4 children. Posaconazole levels were consistently therapeutic in 5/7 (71%) children (range 0.7–2.47 mg/L). Levels in 1 child fell to <0.2 mg/L following the introduction of an interacting drug (rifampicin), and a level of 2.47 mg/L was associated with raised LFTs in another, resulting in discontinuation of posaconazole.

Conclusion In this small cohort, posaconazole was better tolerated than voriconazole for the treatment of Aspergillus or ABPA in children with CF, due mainly to the lack of photosensitivity associated with its use. Posaconazole levels attained from our patients indicate that therapeutic levels can be readily obtained in this patient population. Larger studies are needed to support these conclusions.

References

1. Doring M, Blume O, Haufe S, et al. Comparison of itraconazole, voriconazole, and posaconazole as oral antifungal prophylaxis in paediatric patients following allogeneic hematopoietic stem cell transplantation. Eur J Clin Microbiol Infect Dis2014;33(4):629–38.

2. Bentley S, Gupta A, Balfour-Lynn IM. Subtherapeutic itraconazole and voriconazole levels in children with cystic fibrosis. J Cyst Fibros2013;12:418–9.