Daoud Al-Badriyeh

Clinical utility of voriconazole eye drops in ophthalmic fungal keratitis

Fungal keratitis is one of the major causes of ophthalmic mycosis and is difficult to treat. The range of common antifungal agents available for fungal keratitis remains inadequate and is generally associated with poor clinical outcomes. Voriconazole is a new generation triazole antifungal agent. Only marketed in systemic formulation and, with broad-spectrum activity and high intraocular penetration, voriconazole has demonstrated effectiveness against fungal keratitis. Systemic voriconazole, however, is not without side effects and is costly. Voriconazole eye drops have been prepared extemporaneously and used for the treatment of ophthalmic fungal keratitis. The current article sought to review the literature for evidence related to the effectiveness and safety of topical voriconazole and its corneal penetration into the aqueous humor of the eye. The voriconazole eye drops used are typically of 1% concentration, well tolerated by the eye, and are stable. Despite existing evidence to suggest that the eye drops are effective in the treatment of fungal keratitis, more studies are needed, especially in relation to using the eye drops as first-line and stand-alone treatment, preparation of higher concentrations, and optimal dosing frequency.

Cost-effectiveness evaluation of voriconazole versus liposomal amphotericin B as empirical therapy for febrile neutropenia in Australia.

OBJECTIVES A major randomized clinical trial, evaluating voriconazole versus liposomal amphotericin B (LAMB) as empirical therapy in febrile neutropenia, recommended voriconazole as a suitable alternative to LAMB. The current study sought to investigate the health economic impact of using voriconazole and LAMB for febrile neutropenia in Australia. METHODS A decision analytic model was constructed to capture downstream consequences of empirical antifungal therapy with each agent. The main outcomes were: success, breakthrough fungal infection, persistent baseline fungal infection, persistent fever, premature discontinuation and death. Underlying transition probabilities and treatment patterns were derived directly from trial data. Resource use was estimated using an expert panel. Cost inputs were obtained from the latest Australian representative published sources. The perspective adopted was that of the Australian hospital. Uncertainty and sensitivity analyses were undertaken via the Monte Carlo simulation. RESULTS Compared with voriconazole, LAMB was associated with a net cost saving of AU

Pharmacoeconomic evaluation of voriconazole versus posaconazole for antifungal prophylaxis in acute myeloid leukaemia

1422 (2.9%) per patient. A similar trend was observed with the cost per death prevented and successful treatment. LAMB dominated voriconazole as it resulted in higher efficacy and lower costs when compared with voriconazole. The results were most sensitive to the duration of therapy and the alternative therapy used post discontinuations. In uncertainty analysis, LAMB had 99.8% chance of costing less than voriconazole. CONCLUSIONS In this study, which used the current standard five component endpoint to assess the impact of empirical antifungal therapy, LAMB was associated with cost savings relative to voriconazole.

Stability of extemporaneously prepared voriconazole ophthalmic solution

BACKGROUND Voriconazole and posaconazole are used prophylactically against invasive fungal infection (IFI) in patients with acute myeloid leukaemia (AML). The current study attempted to evaluate the economics of voriconazole versus posaconazole for prophylaxis in AML. METHODS A 6 year (2003-09) retrospective chart review of AML patients was performed at a major Australian tertiary hospital. Patients were followed through the induction stage of chemotherapy, estimating outcome probabilities and prescribing patterns of antifungal prophylaxis. Cost inputs were obtained from the latest Australian sources. A decision analytical model was developed to depict options and consequences involved in the prophylaxis, including success, survival, possible and proven IFIs, and discontinuations due to intolerance. A cost-benefit analysis and an uncertainty study through sensitivity analyses were performed. RESULTS Fifty-six and 38 patients were evaluated in the voriconazole and posaconazole groups, respectively. Baseline demographic characteristics were not significantly different between the study cohorts. Posaconazole was associated with an overall cost saving of AU

Economic impact of caspofungin as compared with liposomal amphotericin B for empirical therapy in febrile neutropenia in Australia

17,458 (29%) per patient over voriconazole. The posaconazole group was associated with lower rate of death, as well as lower probability of discontinuation because of possible infections and intolerance to oral administration. The voriconazole group was associated with fewer proven infections. As per sensitivity analyses, results were highly robust over variations in all costs and probabilities in the model. Monte Carlo simulation suggested a 91.6% chance for posaconazole to cost less than voriconazole. CONCLUSIONS This is the first economic evaluation of voriconazole versus posaconazole; where posaconazole appears to be more cost-beneficial than voriconazole as antifungal prophylaxis in AML.

Successful Salvage Treatment of Scedosporium apiospermum Keratitis with Topical Voriconazole After Failure of Natamycin

PURPOSE The stability of extemporaneously prepared voriconazole ophthalmic solution was studied. METHODS Voriconazole solutions (2% and 1%) were reconstituted from the i.v. formulation. After thorough mixing, 3-mL samples of each of the resulting 2% and 1% solutions were filtered into eyedroppers. Three samples for both solutions were analyzed in triplicate at each time point. The 2% voriconazole ophthalmic solutions were stored at 2-8 degrees C, 25 degrees C, and 40 degrees C. The 1% voriconazole eye drops were stored at 2-8 degrees C. The 2% voriconazole solution samples were analyzed at time 0 and at weeks 1, 2, 4, 8, 16, and 32. The 1% solution samples were analyzed at time 0 and at weeks 6 and 14. Stability was measured using high-performance liquid chromatographic analysis. RESULTS The 2% voriconazole ophthalmic solution demonstrated excellent stability at 2-8 degrees C and 25 degrees C for up to 16 weeks. The voriconazole solution displayed no significant change in pH at all time intervals. No change in visual appearance or clarity was observed in the 2% voriconazole eye drops at any point of the study for all study temperatures. Voriconazole 1% solution was stable at 2-8 degrees C for up to 14 weeks. CONCLUSION Voriconazole 2% (20 mg/mL) solution preserved with 0.01% benzalkonium chloride prepared as alternative antifungal eye drops was stable for 16 weeks when stored at 2-8 degrees C and 25 degrees C and for 8 weeks when stored at 40 degrees C, while voriconazole 1% solution was stable at 2-8 degrees C for up to 14 weeks.

Successful Use of Topical Voriconazole 1% Alone as First-Line Antifungal Therapy Against Candida albicans Keratitis

BACKGROUND In a major clinical trial, caspofungin was as efficacious as liposomal amphotericin B (LAmB) for empirical therapy in febrile neutropenia. The current study sought to evaluate the economic impact of caspofungin as compared with LAmB for febrile neutropenia in Australia. METHODS A decision analytic model was developed to capture the downstream consequences of the empirical antifungal therapy. The main outcomes were success, breakthrough infection, persistent baseline infection, persistent fever, premature discontinuation and death. Underlying transition probabilities and treatment patterns were derived directly from trial data. Resource use was estimated using an expert panel. Cost inputs were obtained from the latest Australian representative sources. The perspective adopted was that of the Australian hospital system. Uncertainty and sensitivity analyses were undertaken via Monte Carlo simulation. RESULTS Caspofungin was associated with a net cost saving of AU

Pharmacoeconomic evaluation of fluconazole, posaconazole and voriconazole for antifungal prophylaxis in patients with acute myeloid leukaemia undergoing first consolidation chemotherapy

7245 (12.6%) per patient over LAmB (AU

Pharmacoeconomic evaluation of caspofungin versus liposomal amphotericin B in empirical treatment of invasive fungal infections in Turkey

50 267 versus AU

Pharmacoeconomics of voriconazole in the management of invasive fungal infections

57 512). A similar trend was observed with cost per success and death prevented (AU