Promacta Study Halted Due to Increased Risk for Portal Venous Thrombosis in Patients With Liver Disease
By Kate Johnson
Medscape Medical News
May 13, 2010 — Eltrombopag (Promacta; GlaxoSmithKline) has been linked to an increased risk for portal venous thrombosis in patients with thrombocytopenia due to chronic liver disease, and the company has halted a study evaluating the drug in this population, the US Food and Drug Administration (FDA) recently announced.
In ELEVATE, a randomized, double-blind, placebo-controlled, multinational study, 6 patients (4%) receiving eltrombopag and 1 patient (1%) receiving placebo "experienced a thrombotic event of the portal venous system," according to an alert sent yesterday from MedWatch, the FDA's safety information and adverse event reporting program.
The FDA reminds healthcare professionals that eltrombopag, a thrombopoietin receptor agonist, "is indicated for the treatment of thrombocytopenia in adult patients with chronic immune (idiopathic) thrombocytopenia purpura (ITP) and is not indicated for the treatment of thrombocytopenia in patients with chronic liver disease."
Clinicians should exercise caution when administering the drug to patients with hepatic disease, the FDA says. Dosing should start at 25 mg once daily, and clinicians should monitor patients closely, particularly those with moderate to severe disease.
The FDA noted that additional caution should be taken when administering eltrombopag to patients with known risk factors for thromboembolism.
"Treatment with Promacta should be aimed at increasing the platelet count to a level that reduces the risk of bleeding; Promacta should not be used in an attempt to normalize the platelet count," the FDA says.
The ELEVATE Study
The alert was preceded by a letter to healthcare professionals from GlaxoSmithKline on May 4, after the company's decision to terminate the ELEVATE study.
ELEVATE was designed to examine the safety and efficacy of eltrombopag in reducing the need for platelet transfusion in thrombocytopenic patients undergoing elective invasive procedures.
Patients with mild, moderate, and severe hepatic impairment of diverse etiology received 75 mg of eltrombopag, or placebo, for 14 days before their procedure.
Of the 6 thrombosis patients who had received eltrombopag, 5 patients experienced the complication at platelet counts above 200,000/μL.
The finding was presented last month at the European Association for the Study of the Liver 45th Annual Meeting. The company has communicated the finding to the trial's investigators and is working with regulatory agencies to include this potential adverse effect in the drug's label.
More information is available on the FDA's MedWatch Web site.
Adverse events related to eltrombopag should be communicated to MedWatch by telephone at 1-800-FDA-1088, by fax at 1-800-FDA-0178, online at http://www.fda.gov/medwatch, or by mail to 5600 Fishers Lane, Rockville, Maryland 20852-9787.
