Trade names Promacta, Revolade MedlinePlus a609011 | AHFS/Drugs.com Monograph Routes ofadministration Oral | |
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License data EU EMA: RevoladeUS FDA: Eltrombopag Pregnancycategory AU: B3US: C (Risk not ruled out) | ||
Eltrombopag (rINN, codenamed SB-497115-GR) is a medication that has been developed for certain conditions that lead to thrombocytopenia (abnormally low platelet counts). It is a small molecule agonist of the c-mpl (TpoR) receptor, which is the physiological target of the hormone thrombopoietin. Eltrombopag was discovered as a result of research collaboration between GlaxoSmithKline and Ligand Pharmaceuticals. Designated an orphan drug in the United States and European Union, it is being manufactured and marketed by GlaxoSmithKline under the trade name Promacta in the USA and is marketed as Revolade in the EU.
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Approvals and indications
Eltrombopag was initially approved by the U.S. Food and Drug Administration on November 20, 2008, for the treatment of thrombocytopenia in patients with chronic immune (idiopathic) thrombocytopenic purpura who have had an insufficient response to corticosteroids, immunoglobulin therapy, or splenectomy.
Eltrombopag received FDA breakthrough treatment designation in February 2014 for patients with aplastic anemia for which immunosuppression has not been successful. It has been shown to produce a trilineage hematopoesis in some patients with aplastic anemia, resulting in increased platelet counts, along with red and white blood cell counts.
On August 24, 2015, the FDA approved eltrombopag (Promacta for oral suspension) for the treatment of thrombocytopenia in pediatric patients 1 year and older with idiopathic thrombocytopenia who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy.
Development
In preclinical studies, the compound was shown to interact selectively with the thrombopoietin receptor, leading to activation of the JAK-STAT signaling pathway and increased proliferation and differentiation of megakaryocytes. Animal studies confirmed that it increased platelet counts. In 73 healthy volunteers, higher doses of eltrombopag caused larger increases in the number of circulating platelets without tolerability problems.
Clinical trials
Eltrombopag has been shown to be effective in two major clinical syndromes: idiopathic thrombocytopenic purpura and cirrhosis due to hepatitis C (in which low platelet counts may be a contraindication for interferon treatment).
After 6 weeks of therapy in a phase III trial, eltrombopag 50 mg/day was associated with a significantly higher response rate than placebo in adult patients with chronic ITP.