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 Toxicology data were obtained from unpublished studies with purified poloxamer 188 and from available data on poloxamer 188 (nonpurified form).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.