Voriconazole therapy in children with cystic fibrosis

Hilliard, Tom; Edwards, Sian; Buchdahl, Roger; Francis, Jackie; Rosenthal, Mark; Balfour‐Lynn, Ian M.; Bush, Andrew; Davies, Jane C.

doi:10.1016/j.jcf.2005.05.019

Cited by 102 publications

(72 citation statements)

References 22 publications

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“…On the other hand, voriconazole-related photosensitivity has rarely been reported in CF children or adult patients [2,[6][7]. This high rate of photosensitivity was not in line with the previous reported ratio of 14% in CF children [2], but closer to 40% in lung-transplanted CF adults [6]. A recent Canadian case report raised the question of voriconazole safety as five out of the six CF children treated with voriconazole presented photosensitivity.…”

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confidence: 76%

“…Voriconazole, a new triazole antifungal, has been recognised as efficient and safe in the treatment of invasive aspergillosis [1][2]. Since it is available orally, voriconazole became the first alternative to itraconazole.…”

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confidence: 99%

“…Skin eruptions [1] have been described in 0.5 to 5.3% of cases in various phase III trials [4], and recently up to 8.3% in an open study on chronic aspergillosis treatment [5]. On the other hand, voriconazole-related photosensitivity has rarely been reported in CF children or adult patients [2,[6][7]. This high rate of photosensitivity was not in line with the previous reported ratio of 14% in CF children [2], but closer to 40% in lung-transplanted CF adults [6].…”

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confidence: 99%

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High frequency of voriconazole-related phototoxicity in cystic fibrosis patients

Rondeau¹,

Couderc²,

Dominique³

et al. 2012

European Respiratory Journal

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To the Editors:Aspergillus fumigatus infection is common in cystic fibrosis (CF) patients and estimates of the rate of allergic bronchopulmonary aspergillosis range from 1-15%. Voriconazole, a new triazole antifungal, has been recognised as efficient and safe in the treatment of invasive aspergillosis [1][2]. Since it is available orally, voriconazole became the first alternative to itraconazole. We began giving voriconazole to CF patients in 2003, and we encountered an unexpectedly high frequency of moderate-tosevere skin reactions, which limited the administration of the drug.We therefore reviewed all the medical files of children (aged ,18 yrs; n572) and adults (n563) followed up in our tertiary CF reference centre between April 2003 and December 2008, in order to estimate the frequency of voriconazole-induced photosensitivity, as previously defined [3]. All the patients who were given voraconazole were selected. Demographic data, cystic fibrosis transmembrane conductance regulator (CFTR) mutations, clinical data, treatment, duration and voriconazole dosage, and related adverse effects (AEs) were collected. Qualitative and quantitative comparisons were analysed using the Chi-squared test and nonparametric Mann-Whitney test, respectively. Multivariate analyses were performed by using stepwise logistic regression.A p-value ,0.05 was considered statistically significant. Statistical analyses were performed using Statistica 8 (StatSoft, MaisonsAlfort, France).

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confidence: 76%

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confidence: 99%

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confidence: 99%

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High frequency of voriconazole-related phototoxicity in cystic fibrosis patients

Rondeau¹,

Couderc²,

Dominique³

et al. 2012

European Respiratory Journal

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“…52 Kolve and others 53 studied 37 immunocompromised pediatric patients with invasive fungal infections and found that 86% of the patients with probable or proven infections and 100% of those with possible infections had a response to treatment and their condition remained stable. In a case series involving patients with cystic fibrosis and recurrent allergic bronchopulmonary aspergillosis, Hilliard and others 54 reported a response to voriconazole therapy.…”

Section: Pediatric Patientsmentioning

confidence: 99%

“…[50][51][52][53][54] In one study, treatment success (as determined by clinical, radiographic, and mycological evidence) was 45% among 58 children (ranging in age from 9 months to 15 years) with aspergillosis, candidiasis, or scedosporiosis. 50 Cesaro and others 51,52 conducted 2 small observational studies in pediatric patients with invasive fungal infections.…”

Section: Pediatric Patientsmentioning

confidence: 99%

Role of Therapeutic Drug Monitoring of Voriconazole in the Treatment of Invasive Fungal Infections

Kuo

Ensom

2009

CJHP

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Background: Voriconazole is a broad-spectrum, second-generation triazole antifungal agent with demonstrated efficacy in the treatment of invasive fungal infections caused by Aspergillus spp. and Candida spp. Given the characteristically poor prognosis of patients with invasive fungal infections and the protracted duration of treatment required, therapeutic monitoring of voriconazole is, in theory, an attractive method to optimize antifungal therapy. Objective:To determine the utility of therapeutic drug monitoring for voriconazole. Methods:A previously published decision-making algorithm was used to assess the currently available literature on therapeutic drug monitoring of voriconazole.Results: Several analytical methods can be used to quantify plasma or serum concentrations of voriconazole. Reasons for therapeutic monitoring of this drug include wide variability both within and between individuals secondary to drug properties, drug-drug interactions, and disease states. Furthermore, voriconazole follows nonlinear pharmacokinetics with saturable hepatic clearance. Another potential factor in favour of therapeutic drug monitoring for voriconazole is genetic polymorphism of CYP2C19, whereby patients who are homozygous for poor metabolism (about 19% of non-Indian Asians) can have 4-fold greater exposure to voriconazole. The concentrations of this drug are also greater in patients with hepatic impairment. Drug-drug interactions with other substrates of CYP2C9, CYP2C19, and CYP3A4 can also alter voriconazole concentrations. However, the correlations between plasma concentrations of voriconazole and its efficacy and toxicity are not well defined. Although lower and upper target thresholds of 0.25-2 mg/L and 4-6 mg/L, respectively, have been suggested, studies to date have not been appropriately designed or powered to reveal any definitive association. Conclusions:Routine therapeutic drug monitoring of voriconazole is not recommended except in certain circumstances, such as lack of response to therapy or evidence of toxicity, in which case selective monitoring of voriconazole concentrations may be of clinical utility. Méthodes : Un algorithme de prise de décision publié a été utilisé pour évaluer la documentation actuellement disponible sur le suivi thérapeutique pharmacologique du voriconazole. Résultats :Plusieurs méthodes analytiques peuvent servir à quantifier les concentrations sériques ou plasmatiques de voriconazole. Les raisons de recourir au suivi thérapeutique pharmacologique de ce médicament sont notamment la grande variabilité intra et interindividuelle attribuable aux propriétés du médicament, aux interactions médicament-médicament et aux affections. De plus, le voriconazole a un comportement pharmacocinétique non linéaire en raison d'une clairance hépatique saturable. Un autre facteur potentiellement en faveur du suivi thérapeutique pharmacologique du voriconazole est le polymorphisme génétique du CYP2C19 qui, chez les patients homozygotes ayant un faible métabolisme (environ 19 % des Asiatiques ...

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Melanoma Associated With Long-term Voriconazole Therapy

Miller¹,

Cowen²,

Nguyen³

et al. 2010

Arch Dermatol

125

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Background: Voriconazole is a triazole antifungal agent approved by the US Food and Drug Administration for serious fungal infections, including with Aspergillus, Fusarium, Pseudallescheria, and Scedosporium species. In initial clinical trials, approximately 2% of patients developed cutaneous reactions, including photosensitivity, cheilitis, and xerosis. Subsequent reports have implicated voriconazole as a cause of severe photosensitivity and accelerated photoaging, pseudoporphyria cutanea tarda, and aggressive squamous cell carcinoma. Observation: We report 5 melanoma in situ lesions in the setting of extreme photosensitivity associated with long-term voriconazole therapy. Conclusions: We recommend surveillance for skin cancer formation in all patients who require long-term voriconazole treatment, particularly those who manifest signs or symptoms of photosensitivity or chronic photodamage. Further study of the mechanism underlying voriconazole photosensitivity and oncogenesis is warranted.

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Voriconazole therapy in children with cystic fibrosis

Abstract: Voriconazole may be a useful adjunctive therapy for ABPA in CF. Voriconazole monotherapy appears to be an alternative treatment strategy when oral corticosteroids may not be suitable.

Cited by 102 publications

References 22 publications

High frequency of voriconazole-related phototoxicity in cystic fibrosis patients

High frequency of voriconazole-related phototoxicity in cystic fibrosis patients

Role of Therapeutic Drug Monitoring of Voriconazole in the Treatment of Invasive Fungal Infections

Melanoma Associated With Long-term Voriconazole Therapy

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