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Safety study and therapeutic drug monitoring of the oral tablet formulation of posaconazole in patients with haematological malignancies

Abstract : PurposePosaconazole is a triazole antifungal widely used for prophylaxis of invasive fungal disease (IFI). Posaconazole tablets allow reaching higher plasma levels than the oral suspension, but safety data with this formulation in real life are scarce. This study aimed at evaluating the safety profile, the pharmacokinetic variability, and the concentration–toxicity relationship of posaconazole tablets in patients with haematological malignancies.MethodsSixty neutropenic patients treated with posaconazole tablets for prophylaxis of IFI were prospectively included in the study. Adverse drug reactions (ADR) were recorded and analyzed by the Regional Pharmacovigilance Centre to assess posaconazole implication. Blood samples were drawn once a week and plasma trough concentrations (C min) were assayed by LC–MS/MS. The rates of ADR by quartile of C min were compared.ResultsEighteen patients (30%) experienced at least one ADR attributed to posaconazole. Liver function test (LFT) abnormalities were encountered in 20% of patients and resulted in four (6.7%) treatment discontinuations. Posaconazole median (range) C min was 1.36 (< 0.1–3.44) µg/mL (inter-patient CV = 43.9%). During follow-up, 28.6% of patients had at least one concentration < 0.7 µg/mL, and 35.7% had at least one concentration > 2 µg/mL. Rates of ADR by quartile of C min were not different.ConclusionsPosaconazole was well tolerated; however, LFT abnormalities were frequent. ADR occurrence was not linked to posaconazole exposure. Because posaconazole concentrations were highly variable, TDM can be helpful to avoid underexposure to the drug and increase its efficacy in preventing IFI. Conversely, a large proportion of patients was overexposed and might have benefited of a dose reduction.
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https://hal-univ-rennes1.archives-ouvertes.fr/hal-01685802
Contributor : Laurent Jonchère Connect in order to contact the contributor
Submitted on : Tuesday, January 16, 2018 - 5:05:42 PM
Last modification on : Tuesday, January 25, 2022 - 6:56:05 PM

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C. Boglione-Kerrien, S. Picard, C. Tron, S. Nimubona, Jean-Pierre Gangneux, et al.. Safety study and therapeutic drug monitoring of the oral tablet formulation of posaconazole in patients with haematological malignancies. Journal of Cancer Research and Clinical Oncology, Springer Verlag, 2018, 144 (1), pp.127-134. ⟨10.1007/s00432-017-2523-2⟩. ⟨hal-01685802⟩

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