Eltrombopag (Promacta), a Thrombopoetin Receptor Agonist for the Treatment of Thrombocytopenia: Current and Future Considerations

Abstract

Thrombocytopenia, a decreased platelet count, is a common clinical feature that may be caused by decreased platelet production or accelerated platelet removal. Accelerated platelet removal may result from various immunologic mechanisms, excessive consumption, or sequestration of platelets in the spleen. Thrombocytopenia can range from a transient, isolated finding to a severe, life-threatening condition. Eltrombopag (SB497115) is a novel, orally bioavailable, small-molecule thrombopoetin receptor agonist that induces differentiation and proliferation of megakaryocytes. Preclinical testing on healthy volunteers shows high drug bioavailability and efficacy in raising platelet counts. The 10-day treatment with eltrombopag increased platelet count up to 1.5 times. The drug is usually tolerated well and serious adverse events and discontinuation are rare. There is an unmet need for this agent, and probably eltrombopag is indeed the "drug of choice" for some limited categories of patients; however, its long-term safety profile is unknown. To evaluate the potential drug development, careful analysis of thrombocytopenia morbidity and prevalence of the applicable for treatment with eltrombopag clinical scenarios is highly warranted. Lack of vascular outcome data with regard to potential excessive activity of these next-generation novel platelets may result in increased thrombotic risks and cause worsened cardiovascular and stroke outcomes may be the major obstacle to the success of this promising agent.