Multicentre study of posaconazole delayed-release tablet serum level and association with hepatotoxicity and QTc prolongation Journal Article
| Authors: | Pettit, N. N.; Miceli, M. H.; Rivera, C. G.; Narayanan, P. P.; Perissinotti, A. J.; Hsu, M.; Delacruz, J.; Gedrimaite, Z.; Han, Z.; Steinbeck, J.; Pisano, J.; Seo, S. K.; Paskovaty, A. |
| Article Title: | Multicentre study of posaconazole delayed-release tablet serum level and association with hepatotoxicity and QTc prolongation |
| Abstract: | Objectives: The association of posaconazole serum concentrations and toxicity is unclear. An assessment of whether levels obtained with the delayed-release tablet (DRT) formulation are correlated with abnormal liver function test (LFT) results and/or QTc prolongation was undertaken. Methods: This was a multicentre, retrospective, observational study of adult patients with cancer between 26 November 2013 and 14 November 2014. Patients were included if they received posaconazole DRT with a posaconazole level obtained between days 5 and 14. Clinical data, including demographics, hepatotoxicmedications, posaconazole levels, LFTs and QTc intervals, were obtained. Association of factors with changes in LFTs and QTc prolongation was assessed using linear and logistic regression. Results: One hundred and sixty-six study patients were included. The median posaconazole level was 1250 (range 110-4220) ng/mL and the median time until level was 6 (range 5-14) days. There was a statistically significant increase in AST (P < 0.001), ALT (P < 0.001), alkaline phosphatase (ALK) (P < 0.001), total bilirubin (TBILI) (P < 0.001) and QTc (P=0.05) from baseline. Posaconazole levels were not associated with increases in AST [b (SE) = -0.33 (2.2), P = 0.88], log ALT [β (SE) = -0.02 (0.03), P=0.63], ALK [β (SE) = 2.2 (2.9), P=0.46] and TBILI [β (SE) = -0.01 (0.04), P = 0.88]. For each additional hepatotoxic medication, there was a mean change in TBILI of 0.13 mg/dL (P = 0.02) and ALK of 7.1 U/L (P = 0.09). No statistically significant association between posaconazole level and QTc interval prolongation was found. Conclusions: Wedid not identify an association between posaconazole serum concentrations and LFT elevations or QTc prolongation. However, some LFTs were found to increase with more hepatotoxic medications administered. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. |
| Journal Title: | Journal of Antimicrobial Chemotherapy |
| Volume: | 72 |
| Issue: | 8 |
| ISSN: | 0305-7453 |
| Publisher: | Oxford University Press |
| Date Published: | 2017-08-01 |
| Start Page: | 2355 |
| End Page: | 2358 |
| Language: | English |
| DOI: | 10.1093/jac/dkx122 |
| PROVIDER: | scopus |
| PUBMED: | 28475803 |
| PMCID: | PMC5890703 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 5 September 2017 -- Source: Scopus |
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