Revolade, Known in the U.S. as Promacta, Tied to Severe Hepatotoxicity Risks

The use of Revolade (eltrombopag) may cause severe hepatotoxicity and potentially deadly fatal liver injury, warns Canada’s health regulator, Health Canada, according to Healthy Canadians, Government of Canada. Revolade, which is a thrombopoietin receptor agonist, is manufactured and marketed by GlaxoSmithKline under the trade name Promacta in the United States. Promacta is marketed as Revolade in the European Union.

Cases of severe drug-induced Revolade liver injury that have led to hepatotoxicity and potentially fatal liver injury have been reported in patients during clinical trials and in the post-marketing period. Patients diagnosed with severe liver impairment are advised against taking Revolade, according to Healthy Canadians.Revolade tablets are prescribed to treat:

• Adult patients diagnosed with chronic immune thrombocytopenia purpura (cITP). Revolade is meant to increase platelet counts in splenectomized patients (patients who have had their spleens removed) who are resistant to first-line treatments such as corticosteroids and immunoglobulins). Revolade may be considered as a second line treatment in adults who are non-splenectomized and unable to undergo surgery.
• Patients with chronic hepatitis C virus (HCV) infection who are also thrombocytopenic (having a low platelet count) to increase platelet counts and enable the introduction and maintenance of interferon-based therapy.
• Adult patients diagnosed with severe aplastic anemia and who have had an insufficient response to immunosuppressive therapy.

Healthcare professionals are advised by Health Canada to conduct certain liver tests over specific periods of time and involving dose adjustments or drug cessation, to help ensure that risks of severe hepatotoxicity and potentially fatal liver injury are reduced. The Canadian Product Monograph for Revolade has been revised to reflect the new safety information.

A systematic analysis of the clinical trial and post-marketing cases from the Revolade development program revealed five cases that fulfilled criteria, known as Hy’s Law criteria, for severe drug-induced liver injury, according to Healthy Canadians. Two cases that fulfilled these criteria were identified in adults diagnosed with cITP; three cases were identified in patients treated for other, non-approved indications. Blood elevation levels occurred within three months of beginning the drug. Meanwhile, in clinical trials involving patients with chronic HCV infection, 11 were treated with Revolade and one percent experienced drug-induced liver injury.

Revolade, marketed in the United States as Promacta, was acquired by the Swiss pharmaceutical company, Novartis, as part of a three-part asset swap with GlaxoSmithKline (GSK) completed in 2015 and involving the Swiss firm that a acquired the GSK oncology business, according to GSK.