http://www.medhelp.org/posts/Hepatitis-C/Eltrombopag-platelet-drug-Trial-Halted-/show/1240951
Eltrombopag (platelet drug) Trial Halted
by mikesimon , May 14, 2010 06:36AM
Tags: platelets, eltrombopag, thrombocytopenia
Thrombocytopenia Trial Halted
By Kristina Fiore, Staff Writer, MedPage Today
Published: May 13, 2010
WASHINGTON -- Drugmaker GlaxoSmithKline terminated a trial of eltrombopag (Promacta) in liver disease patients due to an increase in thrombotic events in the treatment group, the FDA said.
Six patients (4%) taking eltrombopag had a thrombosis of the portal venous system compared with one patient (1%) on placebo, the company said in a letter to healthcare professionals.
The findings, which were reported at the European Association for the Study of the Liver meeting in April, emerged from an analysis of the ELEVATE Study, a randomized, double-blind, placebo-controlled, multicenter trial.
In the trial, patients with thrombocytopenia due to chronic liver disease were randomized to eltrombopag 75mg or matching placebo for 14 days prior to an elective invasive procedure.
The drug is a thrombopoietin receptor agonist and is approved for the treatment of thrombocytopenia in adult patients.
The researchers found an imbalance of thrombosis of the portal venous system in treated patients compared with those on placebo.
Among the six patients in the eltrombopag group who had a portal venous thrombosis, five had it at platelet counts above 200,000/μL, the company said.
GlaxoSmithKline has notified the clinical trial investigators and regulatory agencies and is working with regulatory agencies to add safety information to the label.
The FDA said the drug is indicated for the treatment of thrombocytopenia in adult patients with chronic immune idiopathic thrombocytopenic purpura and is not indicated for the treatment of thrombocytopenia in patients with chronic liver disease.
The agency also added that treatment should be aimed at increasing the platelet count to a level that reduces the risk of bleeding and shouldn't be used in an attempt to normalize the platelet count.
http://tinyurl.com/2a734bb
Promacta is restricted in its use.
http://www.rxlist.com/promacta-drug.htm
Because of the risk for hepatotoxicity and other risks [see WARNINGS AND PRECAUTIONS], PROMACTA (eltrombopag tablets) is available only through a restricted distribution program called PROMACTA (eltrombopag tablets) CARES. Under PROMACTA (eltrombopag tablets) CARES, only prescribers, pharmacies, and patients registered with the program are able to prescribe, dispense, and receive PROMACTA (eltrombopag tablets) . To enroll in PROMACTA (eltrombopag tablets) CARES, call 1-877-9-PROMACTA [see WARNINGS AND PRECAUTIONS].
It was hoped that Promacta was going to be the answer for allowing cirrhotic patients to complete treatment by preventing platelet count from becoming too low due to the side effect of interferon. Unfortunately due to hepatotoxicity and clotting issues that were only realized at the late stages of drug development its promise for person with advanced liver disease has never come to pass.
Is your treatment doctor a hepatologist? You should be treated by a hepatologist not a GP or gastroenterologist. I am assuming you have cirrhosis, due of your low starting platelet count (~ 50,000)? Further damage to your liver is something you want to be careful about.
Platelet transfusions are the most common way the platelet count is increased. Many doctors will stop treatment if the platelet count is below 20,000. But it varies from doctor to doctor. Ask your doctor when he will make you stop. My platelet count went down to about 18,000 and had no unusual bleeding. But as you get in the teens you could develop nose bleeds and bleeding under the skin.
From the Promacta label -
----------------------- WARNINGS AND PRECAUTIONS-----------------
• PROMACTA may cause hepatotoxicity. Increases in serum aminotransferase levels and bilirubin were observed. Liver chemistries must be measured before the initiation of treatment and regularly during treatment. (5.1)
• Exercise caution when administering to patients with hepatic impairment. (5.1,
8.6)
• Because of the risk for hepatotoxicity and other risks, PROMACTA is available only through a restricted distribution program. To enroll in the restricted distribution program, PROMACTA CARES, call 1-877-9-PROMACTA. (5.8)
As the FDA warning states:
Promacta is NOT indicated for the treatment of thrombocytopenia in patients with chronic liver disease.
The agency also added that treatment should be aimed at increasing the platelet count to a level that reduces the risk of bleeding and SHOULDN'T be used in an attempt to normalize the platelet count.
-----------------------------------------------------------------------------------------------------------------------
Risk for Hepatotoxicity
PROMACTA (eltrombopag tablets) administration may cause hepatotoxicity. In the controlled clinical studies, one patient experienced Grade 4 (NCI Common Terminology Criteria for Adverse Events [NCI CTCAE] toxicity scale) elevations in serum liver test values during therapy with PROMACTA (eltrombopag tablets) , worsening of underlying cardiopulmonary disease, and death. One patient in the placebo group experienced a Grade 4 liver test abnormality. Overall, serum liver test abnormalities (predominantly Grade 2 or less in severity) were reported in 11% and 7% of the PROMACTA (eltrombopag tablets) and placebo groups, respectively. In the 3 controlled studies, four patients (1%) treated with PROMACTA (eltrombopag tablets) and three patients in the placebo group (2%) discontinued treatment due to hepatobiliary laboratory abnormalities. Seven of the patients treated with PROMACTA (eltrombopag tablets) in the controlled studies with hepatobiliary laboratory abnormalities were re-exposed to PROMACTA (eltrombopag tablets) in the extension study. Six of these patients again experienced liver test abnormalities (predominantly Grade 1) resulting in discontinuation of PROMACTA (eltrombopag tablets) in one patient. In the extension study, one additional patient had PROMACTA (eltrombopag tablets) discontinued due to liver test abnormalities ( ≤ Grade 3).
Measure serum ALT, AST, and bilirubin prior to initiation of PROMACTA (eltrombopag tablets) , every 2 weeks during the dose adjustment phase, and monthly following establishment of a stable dose. If bilirubin is elevated, perform fractionation. Evaluate abnormal serum liver tests with repeat testing within 3 to 5 days. If the abnormalities are confirmed, monitor serum liver tests weekly until the abnormality(ies) resolve, stabilize, or return to baseline levels. Discontinue PROMACTA (eltrombopag tablets) if ALT levels increase to ≥ 3X the upper limit of normal (ULN) and are:
progressive, or
persistent for 4 weeks, or
accompanied by increased direct bilirubin, or
accompanied by clinical symptoms of liver injury or evidence for hepatic decompensation.
Reinitiating treatment with PROMACTA (eltrombopag tablets) is not recommended. If the potential benefit for reinitiating treatment with PROMACTA (eltrombopag tablets) is considered to outweigh the risk for hepatotoxicity, then cautiously reintroduce PROMACTA (eltrombopag tablets) and measure serum liver tests weekly during the dose adjustment phase. If liver tests abnormalities persist, worsen or recur, then permanently discontinue PROMACTA (eltrombopag tablets) .
Pharmacokinetic evaluations in patients with hepatic impairment show that plasma eltrombopag AUC(0-τ ) increases with increasing degree of hepatic impairment (as measured by Child-Pugh). Exercise caution when administering PROMACTA (eltrombopag tablets) to patients with hepatic impairment (Child-Pugh Class A, B, C). Use a lower starting dose of PROMACTA (eltrombopag tablets) in patients with any degree of hepatic impairment and monitor closely
Best of luck.
Howie