Eltrombopag: A Novel Oral Thrombopoietin Receptor Agonist

OBJECTIVE: To review the pharmacology and pharmacokinetics and evaluate the safety and efficacy of eltrombopag for the treatment of chronic immune (idiopathic) thrombocytopenic purpura (ITP) and thrombocytopenia associated with hepatitis C virus (HCV) cirrhosis. DATA SOURCES: A Cochrane Controlled Trial Register, clinicaltrials.gov, EMBASE, and MEDLINE search was performed (January 1966 March 2010) using the key terms eltrombopag and SB-497115-GR. Searches were limited to published English-language studies in humans and a reference review of the pertinent literature was conducted. STUDY SELECTION AND DATA EXTRACTION: Published pharmacokinetic data and safety and efficacy trials, case reports, and case series on the use of eltrombopag were selected for inclusion. DATA SYNTHESIS: Eltrombopag is a novel second-generation thrombopoietin receptor agonist that was approved by the Food and Drug Administration for the treatment of chronic ITP in patients who had an insufficient response to corticosteroids, intravenous immune globulin, or splenectomy. Eltrombopag has been shown to be superior to placebo in increasing platelet counts, with more patients achieving counts >50 x 10(3)/mu L. One study has also shown eltrombopag to be effective in the treatment of thrombocytopenia associated with HCV cirrhosis. Eltrombopag has a boxed warning related to risk of hepatotoxicity, with criteria for discontinuation in patients with elevated liver enzyme levels or clinical signs of liver damage. As such, close monitoring of laboratory parameters is required, and patients must be registered with the PROMACTA CARES program. CONCLUSIONS: Eltrombopag is effective in increasing platelet counts in patients with chronic ITP and in patients with HCV cirrhosis. In the treatment of ITP, eltrombopag has been studied only for short durations and is more expensive than first-line oral corticosteroids; therefore, it should be considered a second-line agent. More studies are needed to identify a place in therapy for eltrombopag in the treatment of thrombocytopenia associated with HCV cirrhosis.