Voriconazole fibrosis

The exact mechanisms of voriconazole-associated photosensitivity are unknown, but inhibition of retinoid metabolism or a direct phototoxic effect of voriconazole or its N-oxide main metabolite, formed by the action of CYP2C19, has been implicated. There was no significant correlation between the incidence of photosensitivity and voriconazole serum concentrations in six children with allergic bronchopulmonary aspergillosis [3T]. In a retrospective study of 24 lung transplant recipients with cystic fibrosis who took voriconazole, heterozygous carriers of the CYP2C19 2 allele required lower maintenance doses than... 

Markantonis SL, Katelari A, Pappa E, Doudounakis S. Voriconazole pharmacokinetics and photosensitivity in children with cystic fibrosis. J Cyst Fibres 2012 11(3) 246-52. 

Ovetchkine P, Th6oret Y, Quach C. Voriconazole inhibition of vitamin A metabolism are adverse events increased in cystic fibrosis patients Pediatr Pulmonol 2010 45(7) 661-6. 

Liver Hepatotoxicity was retrospectively evaluated in a cohort study in 105 lung transplant recipients taking voriconazole [25 ]. Age less than 40 years, cystic fibrosis, use of azathioprine, history of liver disease and early initiation of voriconazole were associated with hepatotoxicity and in multivariable logistic regression analysis, perioperative initiation of voriconazole was independently associated with hepatotoxicity. 

Skin Cases of voriconazole-induced photosensitivity continue to be reported. In 23 paediatric patients receiving voriconazole with methotrexate, cheilitis and/or photosensitivity occurred in 11 patients [29 ]. The authors could not identify a mechanism for this reaction. Two cases with severe skin toxicity were further described. Another report found retrospectively an unusually high incidence (33%) of voriconazole-associated photosensitivity in immunocompromised children receiving voriconazole, which was associated with a voriconazole dose of >6 mg/kg per dose twice daily [30 ]. A retrospective evaluation of 135 patients with cystic fibrosis demonstrates that these patients seem to be highly photosensitive to voriconazole (incidence 58.1%) and AF508 CFTR mutation might be involved in the development of voriconazole-associated photosensitivity [31 ]. The FIDOS and DoTS descriptions of this reaction are shown in Figure 1. 

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