Itraconazole Prophylaxis in Lung Transplant Recipients Receiving Tacrolimus (FK 506): Efficacy and Drug Interaction

Invasive fungal infections (IFI) are common after lung transplantation and there are limited data for the use of antifungal prophylaxis in these patients. Our aim was to compare the safety and describe the effectiveness of universal prophylaxis with two azole regimens in lung transplant recipients. This is a retrospective study in lung transplant recipients from July 2003 to July 2006 who received antifungal prophylaxis with itraconazole or voriconazole plus inhaled amphotericin B to compare the incidence of hepatotoxicity. Secondary outcomes include describing the incidence of IFI, clinical outcomes after IFI and mortality.Sixty-seven consecutive lung transplants received antifungal prophylaxis, 32 itraconazole and 35 voriconazole and inhaled amphotericin B. There were no significant differences between groups in the acute physiology and chronic health evaluation (APACHE) score at the time of transplantation, demographic characteristics, comorbidities and concomitant use of hepatotoxic medications. Hepatotoxicity occurred in 12 patients receiving voriconazole and inhaled amphotericin B and in no patients receiving itraconazole (p < 0.001). There was no significant difference between groups with regard to the percentage of transplants with IFI, but one case of zygomycosis occurred in a transplant treated with voriconazole. Voriconazole prophylaxis after lung transplantation was associated with a higher incidence of hepatotoxicity and similar clinical effectiveness when compared to itraconazole.

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“…However, there is no uniform approach to the prevention of these fungal infections (8)(9)(10). (11)(12)(13)(14)(15) Figure 1).…”

Section: Lung Transplantation Is a Complex Procedures Indicated In Patmentioning

confidence: 99%

“…We think the use of inhaled amphotericin B was unlikely to contribute to the hepatotoxicity. In a retrospective study by Hussein et al, (17) (11,21,35,36). Despite these differences, itraconazole was well tolerated and with a low degree of hepatotoxicity.…”

Section: During the Antifungal Prophylaxis Period 11 Transplants Wermentioning

confidence: 99%

Antifungal Prophylaxis with Voriconazole or Itraconazole in Lung Transplant Recipients: Hepatotoxicity and Effectiveness

Cadena

Levine

Angel

et al. 2009

American Journal of Transplantation

104

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“…Most are retrospective 7,20,22,32-45 and noncomparative. 22,33,34,36,38,39,[42][43][44][45][46][47][48] Of comparative trials, 7,20,[31][32][33]35,37,40,41,45,49,50 all used a nonrandomized, sequential design, with the exception of Drew et al 51 Although the majority of studies evaluated inhaled formulations of amphotericin B alone, 7,22,31,35,47,51 in combination with, 20,40,43 or as compared with other antifungals, 22,36,37,40,51 universal or targeted 20,50 prophylaxis with oral administration of fluconazole, 20,36,40,49 itraconazole, 20,33,34,…”

Section: Efficacy Of Antifungal Prophylaxis Regimensmentioning

confidence: 99%

Antifungal Prophylaxis in Lung Transplant Recipients

Patel

Eschenauer²,

Stuckey³

et al. 2016

Transplantation

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Invasive fungal infection remains a serious postoperative complication in lung transplant recipients and is associated with significant morbidity and mortality. Although most lung transplant centers use antifungal prophylaxis, consensus on the strategy, choice of antifungal agent(s), route of administration, and duration of prophylaxis have not been established. This review provides an overview of the epidemiology and risk factors for common fungal infections seen in lung transplant recipients, evaluates the clinical efficacy and toxicity of the various antifungal agents used to prevent infection, and offers recommendations and opportunities for future research. Currently available data evaluating the efficacy of antifungal prophylaxis strategies is limited by a lack of prospective, randomized clinical trial data and variability in patient populations, prophylactic and immunosuppressive strategies, dosing, durations of use of antifungal agents, and definitions of invasive infection. There is controversy regarding significant risk factors for invasive fungal infection, which has limited the development and validation of targeted prophylactic strategies. Inhaled formulations of amphotericin B remain the most widely studied option for universal prophylaxis and have been shown to be effective in reducing the incidence of invasive Aspergillosis as compared with no prophylaxis. Concern over early postoperative extrapulmonary infection may suggest a benefit of initial prophylaxis with a systemic azole. Long-term use of systemic antifungals is not optimal due to emerging evidence of long-term toxicities. Multicenter, randomized trials are needed to ascertain the optimal prophylactic strategy in lung transplant recipients. New agents and delivery mechanisms may offer additional opportunities for comparative research.

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“…Although studies documenting the effi cacy of itraconazole capsules as prophylaxis for IA in heart and lung transplant recipients are more encouraging [26,35], oral bioavailability is a significant concern. Systemic availability of itraconazole in lung transplantation was evaluated by serially measuring itraconazole levels in lung transplant patients who received itraconazole for prophylaxis or therapy, and absorption was highly variable [36].…”

Section: Azoles: Fl Uconazole Itraconazole Posaconazole and Voricomentioning

confidence: 99%

Prophylaxis of invasive mycoses in solid organ transplantation

Radack

Alexander

2009

Curr Infect Dis Rep

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Solid organ transplantation is emerging as a lifesaving procedure for increasing numbers of patients, and invasive fungal infections are a significant cause of mortality and morbidity for patients undergoing such procedures. Risks for developing these infections are continuing to evolve, leading to shifts in the epidemiology of invasive mycoses occurring after transplantation. Targeting preventive efforts to select solid organ transplantation groups at highest risk for invasive fungal infections is critical to optimizing prophylaxis strategies. The epidemiology of posttransplantation fungal infections, antifungal drug interactions and side effects, and new diagnostic capabilities should be considered when choosing an approach to antifungal prophylaxis for this population.

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Itraconazole Prophylaxis in Lung Transplant Recipients Receiving Tacrolimus (FK 506): Efficacy and Drug Interaction

Cited by 53 publications

References 20 publications

Antifungal Prophylaxis with Voriconazole or Itraconazole in Lung Transplant Recipients: Hepatotoxicity and Effectiveness

Antifungal Prophylaxis with Voriconazole or Itraconazole in Lung Transplant Recipients: Hepatotoxicity and Effectiveness

Antifungal Prophylaxis in Lung Transplant Recipients

Prophylaxis of invasive mycoses in solid organ transplantation

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