Eltrombopag is a thrombopoietin (TPO) receptor agonist that initiates signaling cascades by binding to the transmembrane domain
of the human TPO receptor, thereby inducing proliferation and differentiation of megakaryocytes. This agent was approved on
November 20, 2008, for the treatment of thrombocytopenia in patients with chronic immune (idiopathic) thrombocytopenic purpura
(ITP) who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy.
Efficacy. The efficacy of eltrombopag was assessed in 2 randomized, double-blind, placebo-controlled trials (Studies 1 and 2) and in
an open-label extension study. Studies 1 and 2 enrolled patients who had completed ≥1 previous ITP therapy and had a platelet
count <30×109 /L. Patients were randomized to treatment with eltrombopag (Study 1, eltrombopag 50 mg/d; Study 2, eltrombopag 30, 50, or
75 mg/d) or placebo for ≤6 weeks. The primary efficacy end point was response rate, defined as an increase in platelet count
to ≥50×109 /L. In Study 1, 59% of patients treated with eltrombopag 50 mg/d demonstrated a response rate versus 16% of placebo-treated
patients (P<.001); in Study 2, 70% of patients treated with eltrombopag 50 mg/d demonstrated a response rate versus 11% of placebo-treated
patients (P<.001). In the open-label extension study, 109 patients who had completed a previous clinical trial of eltrombopag were enrolled;
74 patients completed 3 months of treatment, 53 completed 6 months of treatment, and 3 completed 1 year of treatment with
eltrombopag. The median platelet count was 74×109 /L at 3 months, 67×109 /L at 6 months, and 95×109 /L at 9 months.
Safety. This agent is available only through a restricted distribution program. Treatment with eltrombopag may cause hepatotoxicity.
Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and bilirubin levels should be measured before and
during treatment. TPO receptor agonists increase the risk for development or progression of reticulin fiber deposition within
bone marrow. Excessive increases in platelet counts may lead to thrombotic/thromboembolic complications during treatment.
Stimulation of the TPO receptor may increase the risk of hematologic malignancies. The most common adverse events associated
with eltrombopag treatment include nausea, vomiting, menorrhagia, myalgia, paresthesia, and cataract.
Dosing. Eltrombopag should be initiated at a dose of 50 mg/d; in patients of East Asian ancestry or with moderate-to-severe hepatic
impairment, eltrombopag should be initiated at 25 mg/d. The dose should then be adjusted to maintain a platelet count of ≥50×109 /L as necessary to reduce bleeding risk. The maximum dose is 75 mg/d. If the platelet count is <50×109 /L after ≥2 weeks of therapy, the dose should be increased by 25 mg/d. If the platelet count increases to ≥200×109 /L but ≤400×109 /L, the dose should be reduced by 25 mg/d. If the platelet count increases to >400×109 /L, eltrombopag should be discontinued; once the platelet count reaches <150×109 /L, therapy can be reinitiated at a dose reduced by 25 mg/d. If the platelet count reaches >400×109 /L after 2 weeks of treatment with the lowest dose of eltrombopag, therapy should be permanently discontinued. 
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