Liposomal amphotericin B: clinical experience and perspectives.

While amphotericin B deoxycholate (Fungizone, Apothecon Pharmaceuticals) has been considered by many to be the gold standard for the treatment for numerous invasive fungal infections for over 45 years, toxicities associated with its use often necessitate treatment modification or discontinuation. Lipid-based formulations, including liposomal amphotericin B (AmBisome, Fujisawa Healthcare, Inc.), were developed to decrease many of these toxicities while retaining broad antifungal spectrum and potency of amphotericin B. In clinical trials, liposomal amphotericin B has demonstrated efficacy comparable to that of amphotericin B deoxycholate while reducing the incidence of treatment-related nephrotoxicity, electrolyte-wasting, and infusion-related reactions. In addition, recent clinical trials have also compared liposomal amphotericin B with other antifungal classes. Acquisition costs of liposomal amphotericin B are substantially higher than those of amphotericin B deoxycholate and other antifungals. While pharmacoeconomic analyses consider outcomes and other treatment-related costs, they have yet to clearly demonstrate the cost-effectiveness of liposomal amphotericin B when compared with amphotericin B deoxycholate or other antifungal agents. This review will focus primarily on recent liposomal amphotericin B experience and attempt to put its use into perspective considering other available antifungal agents.

Optimal antithrombotic management of anticoagulated patients with a history of myocardial infarction.

A common clinical dilemma exists for optimal antithrombotic management of a patient requiring oral anticoagulation (such as venous thromboembolism) and continued secondary myocardial infarction prophylaxis. Often aspirin will be continued concomitantly with the indicated oral anticoagulation therapy; however, additional benefits and increased risks of this practice have not been established. A systematic literature review was conducted to determine the benefits and risks of antithrombotic treatment strategies. Five clinical trials met the inclusion criteria and were evaluated to answer this clinical question.

Purified poloxamer 188 for sickle cell vaso-occlusive crisis.

OBJECTIVE: To review available literature on the pharmacology, pharmacokinetics, efficacy, toxicology, adverse effects, drug interactions, and dosage guidelines for purified poloxamer 188, a product in Phase III trials. DATA SOURCES: Reviewers searched the following databases for English-language studies: MEDLINE (1966-November 2003), International Pharmaceutical Abstracts (1970-November 2003), and the Cochrane Library Database (3rd quarter 2003). Key search terms included purified poloxamer 188, Flocor, CRL-5861, poloxamer 188, RheothRx, and pluronic F-68. STUDY SELECTION AND DATA EXTRACTION: Data on efficacy, adverse effects, and pharmacokinetics were obtained from randomized, open-label, and blinded clinical trials. Toxicology data were obtained from unpublished studies with purified poloxamer 188 and from available data on poloxamer 188 (nonpurified form). DATA SYNTHESIS: Purified poloxamer 188 is a highly purified form of the nonionic block copolymer poloxamer 188. It lowers blood viscosity, decreases red blood cell (RBC) aggregation, and decreases friction between RBCs and vessel walls to increase microvascular blood flow and decrease cell injury. In clinical trials, purified poloxamer 188 demonstrated safety, but little efficacy for the treatment of sickle cell vaso-occlusive crisis. Increased efficacy has been shown in patients on concurrent hydroxyurea therapy and those <15 years of age. CONCLUSIONS: Purified poloxamer 188 represents a new approach to the management of the sickle cell vaso-occlusive crisis. Children and patients on hydroxyurea may benefit most from purified poloxamer 188 therapy. Further studies are needed to confirm its efficacy and to determine whether the drug decreases sickle cell disease severity and complications.