Pharmacoeconomics of voriconazole in the management of invasive fungal infections

Al‐Badriyeh, Daoud; Heng, Siow Chin; Neoh, Chin Fen; Slavin, Monica A; Stewart, Kay; Kong, David Chee Ming

doi:10.1586/erp.10.69

Cited by 7 publications

(4 citation statements)

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“…Their data suggest nonlinear corneal absorption of voriconazole, which is consistent with the results of our previous studies that showed that the penetration of voriconazole via an intact cornea is unlikely to be concentration dependent for a concentration range between 1% and 2% (5, 6). The ocular kinetics of topical voriconazole seem to reflect the nonlinearity of the voriconazole pharmacokinetics profile when administered systemically (10). In addition, our results show a slower decline in voriconazole aqueous humor concentrations than was previously reported (elimination t 1/2 ϭ 0.82 h) by Senthilkumari et al (8), who adopted a one-compartment model.…”

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confidence: 68%

Open-Label Study of Absorption and Clearance of 1% Voriconazole Eye Drops

Neoh

Leung

Chan

et al. 2016

Antimicrob Agents Chemother

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h Twenty participants undergoing elective cataract surgery received 1% voriconazole eye drops (1 drop per eye) either 20, 40, 60, or 80 min before surgery. Median voriconazole concentrations of 1.9 to 3.2 mg/liter in aqueous humor samples were attained over the first 80 min, which were higher than in vitro MIC 90 values for typical fungi that cause keratitis. Fungal keratitis remains one of the most difficult-to-treat corneal infections and accounts for approximately 50% of infectious keratitis cases in developing countries (1). The filamentous fungi Aspergillus and Fusarium spp. are the two most frequently encountered causative pathogens (2).Voriconazole is increasingly used as a first-line treatment for ocular fungal infections (3) given its excellent in vitro activity against a wide variety of keratitis isolates (4), including less common fungi (e.g., Curvularia and Acremonium spp.). Topically administered 1% and 2% voriconazole eye drops have been documented to achieve good intraocular penetration in noninflamed (5, 6) and inflamed eyes (7). However, the voriconazole concentrations observed in the aqueous humor samples of patients receiving 2% voriconazole eye drops (6) were similar to that reported for the 1% voriconazole eye drops (5) when the same dosing frequency was used (i.e., total of four once-hourly doses). This suggests that increasing the concentration of voriconazole eye drops from 1% to 2% does not result in higher voriconazole concentrations in the aqueous humor of noninflamed human eyes. The extent of voriconazole clearance from the eye after topical administration might have been the key factor behind this observation, but this issue has largely remained unexplored, except in a recent ocular kinetic study by Senthilkumari et al. (8); therefore, data on this remain limited. The availability of such data is important for optimizing the dosing of voriconazole eye drops. Accordingly, we investigated the change in voriconazole concentrations in the aqueous humor of human eyes over time after topical administration of 1% voriconazole eye drops.Between April 2009 and April 2011, participants who were Ն18 years old and were scheduled for elective cataract surgery at the Royal Victorian Eye and Ear Hospital (RVEEH) were recruited. Excluded were subjects with a history of inflammation of the eye (uveitis) to undergo surgery, with a history of kidney or liver failure, who were breastfeeding, pregnant, or trying to conceive, who had an allergy to voriconazole or benzalkonium chloride, or who were using medications known to interact with voriconazole. Written informed consent was obtained from participants prior to enrollment. The study was approved by the ethics committees of RVEEH and Monash University.One-percent voriconazole eye drops were prepared aseptically from Vfend injections as previously described (6). All eye drops were stable for at least 14 weeks when stored at 2 to 8°C (9). Consenting participants each received a single drop (50 l) of 1% voriconazole to the eye to undergo surgery 20 min (a...

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supporting

confidence: 68%

Open-Label Study of Absorption and Clearance of 1% Voriconazole Eye Drops

Neoh

Leung

Chan

et al. 2016

Antimicrob Agents Chemother

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“…No prior studies have compared the cost-effectiveness of isavuconazole vs. voriconazole in the treatment of IA; however, there are multiple studies comparing voriconazole to other IA treatments [13, 38]. Those studies have concluded that voriconazole is the preferred therapy for IA in terms of cost-effectiveness.…”

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confidence: 99%

Cost-Effectiveness Analysis of Isavuconazole vs. Voriconazole as First-Line Treatment for Invasive Aspergillosis

et al. 2016

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IntroductionInvasive aspergillosis (IA) is associated with a significant clinical and economic burden. The phase III SECURE trial demonstrated non-inferiority in clinical efficacy between isavuconazole and voriconazole. No studies have evaluated the cost-effectiveness of isavuconazole compared to voriconazole. The objective of this study was to evaluate the costs and cost-effectiveness of isavuconazole vs. voriconazole for the first-line treatment of IA from the US hospital perspective.MethodsAn economic model was developed to assess the costs and cost-effectiveness of isavuconazole vs. voriconazole in hospitalized patients with IA. The time horizon was the duration of hospitalization. Length of stay for the initial admission, incidence of readmission, clinical response, overall survival rates, and experience of adverse events (AEs) came from the SECURE trial. Unit costs were from the literature. Total costs per patient were estimated, composed of drug costs, costs of AEs, and costs of hospitalizations. Incremental costs per death avoided and per additional clinical responders were reported. Deterministic and probabilistic sensitivity analyses (DSA and PSA) were conducted.ResultsBase case analysis showed that isavuconazole was associated with a $7418 lower total cost per patient than voriconazole. In both incremental costs per death avoided and incremental costs per additional clinical responder, isavuconazole dominated voriconazole. Results were robust in sensitivity analysis. Isavuconazole was cost saving and dominant vs. voriconazole in most DSA. In PSA, isavuconazole was cost saving in 80.2% of the simulations and cost-effective in 82.0% of the simulations at the $50,000 willingness to pay threshold per additional outcome.ConclusionIsavuconazole is a cost-effective option for the treatment of IA among hospitalized patients.FundingAstellas Pharma Global Development, Inc.Electronic supplementary materialThe online version of this article (doi:10.1007/s12325-016-0443-1) contains supplementary material, which is available to authorized users.

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“…Fusarium species possesses several virulence factors, including the production of tricothecene and other mycotoxins. These mycotoxins can suppress humoral and cellular immunity, and cause break down of tissue [ 4 ]. Such skin breakdown may precede infection by up to one year [ 2 ].…”

mentioning

confidence: 99%

“…If Fusarium species are identified in culture or biopsy, aggressive debridement should be performed and antifungal therapy should be administered. Previous guidelines recommended amphotericin B for treatment of fungal infections, including Fusarium infection, however, in a recent analysis, voriconazole was recommended as the most cost-effective therapy [ 4 ]. Treatment of cutaneous fusariosis is usually successful.…”

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confidence: 99%