Network Meta-analysis and Pharmacoeconomic Evaluation of Fluconazole, Itraconazole, Posaconazole, and Voriconazole in Invasive Fungal Infection Prophylaxis.

Invasive fungal infections (IFIs) are associated with high mortality rates and large economic burdens. Triazole prophylaxis is used for at-risk patients with hematological malignancies or stem cell transplants. We evaluated both the efficacy and the cost-effectiveness of triazole prophylaxis. A network meta-analysis (NMA) of randomized controlled trials (RCTs) evaluating fluconazole, itraconazole capsule and solution, posaconazole, and voriconazole was conducted. The outcomes of interest included the incidences of IFIs and deaths. This was coupled with a cost-effectiveness analysis from patient perspective over a lifetime horizon. Probabilities of transitions between health states were derived from the NMA. Resource use and costs were obtained from the Singapore health care institution. Data on 5,505 participants in 21 RCTs were included. Other than itraconazole capsule, all triazole antifungals were effective in reducing IFIs. Posaconazole was better than fluconazole (odds ratio [OR], 0.35 [95% confidence interval [CI], 0.16 to 0.73]) and itraconazole capsule (OR, 0.25 [95% CI, 0.06 to 0.97]), but not voriconazole (OR, 1.31 [95% CI, 0.43 to 4.01]), in preventing IFIs. Posaconazole significantly reduced all-cause deaths, compared to placebo, fluconazole, and itraconazole solution (OR, 0.49 to 0.54 [95% CI, 0.28 to 0.88]). The incremental cost-effectiveness ratio for itraconazole solution was lower than that for posaconazole (Singapore dollars [SGD] 12,546 versus SGD 26,817 per IFI avoided and SGD 5,844 versus SGD 12,423 per LY saved) for transplant patients. For leukemia patients, itraconazole solution was the dominant strategy. Voriconazole was dominated by posaconazole. All triazole antifungals except itraconazole capsule were effective in preventing IFIs. Posaconazole was more efficacious in reducing IFIs and all-cause deaths than were fluconazole and itraconazole. Both itraconazole solution and posaconazole were cost-effective in the Singapore health care setting.

Prolonged argatroban clearance in a critically ill patient with heparin-induced thrombocytopaenia.

This is a case of argatroban use in a critically ill patient with heparin-induced thrombocytopaenia (HIT), presenting with unexpectedly prolonged drug clearance possibly secondary to hepatic congestion due to reduced cardiac contractility. A 63-year-old woman from Asia with end-stage renal failure was hospitalised in the critical care unit with non-ST elevation myocardial infarction with underlying triple vessel disease. She was subsequently started on intravenous unfractionated heparin infusion after an intra-aortic balloon pump was inserted. Six days after the initiation of heparin, she developed HIT and argatroban was started for treatment of HIT. Despite starting on the recommended dose of 2µg/kg/min, she developed significantly prolonged activated partial thromboplastin time (aPTT) with delayed clearance. Argatroban was stopped 14 hours after time of initiation in view of the markedly prolonged aPTT (in the range of 145 s), and levels only normalised at approximately 60 hours after argatroban was stopped.