Effect of voriconazole on the pharmacokinetics of cyclosporine in renal transplant patients

Romero, Alain; Pogamp, P. Le; Nilsson, Lars‐Göran; Wood, Nolan

doi:10.1067/mcp.2002.121911

Cited by 162 publications

(97 citation statements)

References 16 publications

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“…39 An empiric dose reduction of 50% for CYA and 66% for tacrolimus has been proposed, along with close monitoring for a week after beginning and finishing treatment with voriconazole. 15,39,40 The combination of voriconazole and sirolimus is contraindicated according to product information, 41 but sirolimus doses reduced by 70-90% have been used safely in combination with voriconazole. [42][43][44] In our study, no ADE was observed in a patient administered sirolimus (3 mg) as the initial dose, followed by 1 mg every 3 days in combination with voriconazole.…”

Section: Discussionmentioning

confidence: 99%

Drug interactions and adverse events associated with antimycotic drugs used for invasive aspergillosis in hematopoietic SCT

Egger

Meier

Leu

et al. 2009

Bone Marrow Transplant

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The aim of this study was to assess the frequency of potential drug-drug interactions (pDDIs) and adverse drug events (ADEs) associated with antimycotics in hospitalized patients with hematopoietic SCT (HSCT). Of the 120 HSCT recipients evaluated, 36 received antimycotics. A total of 124 ADEs were recorded in 32 of the 36 patients treated, with 54 ADEs being possibly and 9 probably related to antimycotics. Of the treatments with amphotericin B, 93% were associated with one or more possible and 36% with probable ADEs. The corresponding figures for lipid-based amphotericin B were 100% and 7%, for voriconazole 68% and 11% and for caspofungin 70% and 0%. A total of 57 potentially severe DDIs associated with antimycotics were detected in 31 of the 36 patients. Of these, 14 DDIs were a possible cause of an ADE and 5 (4 times a combination of voriconazole with CYA and once a combination of CYA with conventional amphotericin B) were probably related. Although the prevalence of pDDIs and ADEs is high in HSCT patients, ADEs related with a high probability to treatment with antimycotics are rare. Regarding the high prevalence of pDDIs, our findings underscore the importance of close monitoring of laboratory and clinical parameters, as well as dose adjustment for critical drugs, in patients with HSCT.

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Section: Discussionmentioning

confidence: 99%

Drug interactions and adverse events associated with antimycotic drugs used for invasive aspergillosis in hematopoietic SCT

Egger

Meier

Leu

et al. 2009

Bone Marrow Transplant

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“…[5][6][7][8] However, the drug interaction between voriconazole and calcineurin inhibitors has been systematically examined only in a limited number of renal transplant recipients (CsA) and in healthy subjects (tacrolimus), and documented sporadically in a few case reports. [7][8][9][10][11][12] In particular, the drug interaction between voriconazole and tacrolimus has not been systematically evaluated in patients to this date. In spite of such limited data, a uniform dose reduction of calcineurin inhibitors on initiating voriconazole (1/2 for CsA, 1/3 for tacrolimus) has been recommended by the manufacturer.…”

Section: Introductionmentioning

confidence: 99%

Drug interaction between voriconazole and calcineurin inhibitors in allogeneic hematopoietic stem cell transplant recipients

Mori

Aisa

Kato

et al. 2009

Bone Marrow Transplant

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Although voriconazole has been shown to interact with calcineurin inhibitors, this interaction has not been thoroughly examined. The purpose of this study was to evaluate the drug interaction between voriconazole and calcineurin inhibitors among recipients of allogeneic hematopoietic stem cell transplantation (HSCT). Twenty-one recipients of allogeneic HSCT were evaluated. Those recipients had been on CsA (n ¼ 10) or tacrolimus (n ¼ 11) when voriconazole (400 mg per day orally, or 8 mg/kg per day, i.v.) was initiated. Trough concentrations of calcineurin inhibitors were measured before and periodically after initiating voriconazole to determine the concentration/dose (C/D) ratio of calcineurin inhibitors. Median C/D ratio significantly increased by initiating voriconazole: from 86.0 (range, 43.5-178.8) to 120.2 (range, 86.1-379.4) in CsA (Po0.05), and from 595.9 (range, 51.3-1643.3) to 890.7 (range, 94.1-4658.3) (ng/ml)/(mg/kg) in tacrolimus (Po0.01). Median increases in the C/D ratio did not differ significantly between CsA and tacrolimus (82.1%, ranging from À9.4 to 266.9% vs 115.6%, ranging from 25.4 to 307.6%). These results indicate that voriconazole alters the blood concentration of calcineurin inhibitors with a wide range of interindividual variability after allogeneic HSCT. Dose adjustment of calcineurin inhibitors on initiating voriconazole should not be decided uniformly, but determined on an individual basis by close monitoring of their blood concentrations.

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“…In one study coadministration of voriconazole and tacrolimus elevated trough tacrolimus levels in one liver transplant patient nearly ten-fold [100], and in another study tacrolimus levels were significantly increased 2.2-fold when coadministered with voriconazole [101]. In a study of renal transplant patients, concomitant administration of voriconazole with cyclosporine also resulted in a 1.7-fold increase in the geometric mean for cyclosporine area under the plasma concentration-time curve, so it is recommended that the cyclosporine dose be halved and levels monitored frequently [102].…”

Section: Toxicities Side Effects and Drug Interactionsmentioning

confidence: 99%

Triazole Use in the Nursery: Fluconazole, Voriconazole, Posaconazole, and Ravuconazole

Watt¹,

Manzoni²,

Cohen‐Wolkowiez³

et al. 2013

Current Drug Metabolism

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Invasive fungal infections in infants admitted to the neonatal intensive care unit are common and often fatal. The mainstay of therapy against invasive fungal infections is antifungal agents. Over the last two decades, the development and approval of these drugs evolved tremendously, and the azole class emerged as important agents in the treatment and prevention of invasive fungal infections. Among the azoles, fluconazole has been used extensively due to its favorable pharmacokinetics, excellent activity against Candida spp, and safety profile. This drug has been well studied in children but data for its use in infants are largely limited to Candida prophylaxis studies. Voriconazole, a second generation triazole, has excellent activity against Candida and Aspergillus spp. However, data on its use in neonates are extremely limited. Posaconazole and Ravuconazole are the newest agents of the triazole family. The antimicrobial spectrum of posaconazole is similar to voriconazole, but with additional activity against zygomycetes. Experience with posaconazole in children is very limited, and there are no reports of its use in infants. Ravuconazole is not approved for use by the FDA but studies in animals and humans show that it is often fungicidal and has favorable pharmacokinetics. In conclusion, the management of invasive fungal infections has progressed greatly over the last two decades with the azole antifungals playing a significant role. Related to this class, future research is needed in order to better assess dosing, safety, schedules and areas of use of these agents in infants admitted to the neonatal intensive care unit.

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Effect of voriconazole on the pharmacokinetics of cyclosporine in renal transplant patients

Cited by 162 publications

References 16 publications

Drug interactions and adverse events associated with antimycotic drugs used for invasive aspergillosis in hematopoietic SCT

Drug interactions and adverse events associated with antimycotic drugs used for invasive aspergillosis in hematopoietic SCT

Drug interaction between voriconazole and calcineurin inhibitors in allogeneic hematopoietic stem cell transplant recipients

Triazole Use in the Nursery: Fluconazole, Voriconazole, Posaconazole, and Ravuconazole

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