Approved November 20, 2008

ELTROMBOPAG
(FDA Category 1P)

PROMACTA(R) (GlaxoSmithKline) is a thrombopoietin receptor agonist

DOSING INFORMATION: The starting dose is 50 mg orally once daily on an empty stomach. In patients of East Asian ancestry (Chinese, Japanese, Taiwanese, or Korean) or in patients with moderate to severe hepatic impairment, the starting dose is 25 mg orally once daily. Adjust the dose to reduce the risk of bleeding and to achieve and maintain a platelet count of 50 x 10(9)/L or more. The maximum daily dose is 75 mg/day. If the platelet count fails to increase after 4 weeks at the maximum dose then discontinue eltrombopag.

PHARMACOKINETICS: Bioavailability was estimated to be at least 52%. Plasma concentrations are reduced in the presence of polyvalent cations (eg, aluminum, magnesium). Protein binding is greater than 99%. Eltrombopag is not a substrate for p-glycoprotein or OATp1B1. Eltrombopag is extensively metabolized. CYP1A2, CYP2C8, UGT1A1, and UGT1A3 are responsible for the majority of metabolism. Feces is the main route of excretion (59%). The half-life is 26 to 35 hrs. East Asians experience a greater exposure and pharmacodynamic response to eltrombopag.

CAUTIONS: Hepatotoxicity, new or worsening bone marrow fibrosis, and bone marrow reticulin formation may occur . Thrombotic and thromboembolic complications may result from excessive platelet count increases. Thrombocytopenia has worsened following eltrombopag discontinuation. Common adverse effects include nausea, vomiting, menorrhagia, myalgia, paraesthesia, cataract, dyspepsia, ecchymosis, thrombocytopenia, increase ALT/AST and conjunctival hemorrhage.

FDA APPROVED INDICATIONS: Indicated for the treatment of thrombocytopenia in patients with chronic immune (idiopathic) thrombocytopenic purpura who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy.