Introduction
Eltrombopag is used to treat low blood platelet counts in adults with chronic immune (idiopathic) thrombocytopenia (ITP), when certain other medicines, or surgery to remove the spleen, have not worked well enough. ITP is a condition that may cause unusual bruising or bleeding due to an abnormally low number of platelets in the blood. Eltrombopag has also been recently approved (late 2012) for the treatment of thrombocytopenia (low blood platelet counts) in patients with chronic hepatitis C to allow them to initiate and maintain interferon-based therapy.
Uses
Eltrombopag is a thrombopoietin receptor agonist used to treat thrombocytopenia or aplastic anemia associated with various etiologies.
Thrombopoietin receptor agonists are pharmaceutical agents that stimulate platelet production in the bone marrow. In this, they differ from the previously discussed agents that act by attempting to curtail platelet destruction.
Associated Conditions
Mechanism of Action
Eltrombopag is an orally bioavailable, small-molecule TPO-receptor agonist that interacts with the transmembrane domain of the human TPO-receptor. Eltrombopag is a stimulator of STAT and JAK phosphorylation. Unlike recombinant TPO or romiplostim, Eltrombopag does not activate the AKT pathway in any way. It should be noted that when given to patients with aplastic anemia, other lineages besides platelet count were increased, suggesting that either eltrombopag enhanced the effect of TPO in vivo; or there is a yet uncovered mechanism of action at work.
Absorption
Peak absorption of Eltrombopag occurs around 2-6 hours following oral administration, and the total oral absorption of drug-related material following a 75 mg dose was estimated to be at least 52%.
Volume of Distribution
Based on a radiolabel study, the concentration of eltrombopag in blood cells is approximately 50% to 79% of plasma concentrations.
Protein Binding
Eltrombopag is highly protein bound (>99%).
Route of Elimination
Eltrombopag is eliminated primarily via the feces (59%), along with 31% being renally excreted.
Half Life
About 21-32 hours in healthy patients. About 26-35 hours in patients with idiopathic thrombocytopenic purpura.
Toxicity
Eltrombopag may cause hepatotoxicity, especially if administered in combination with interferon and ribavirin in patients with chronic hepatitis C (may increase the risk of hepatic decompensation).
Food Interactions
- Avoid multivalent ions. Polyvalent cations in food or supplements will be chelated by eltrombopag; therefore, they should be separated by 4 hours before or 2 hours after taking eltrombopag.
- Take on an empty stomach. Separate the administration of eltrombopag from food by at least 1 hour before and 2 hours after eating.
Dosage
Persistent or chronic immune thrombocytopenia: Use the lowest dose of Eltrombopag to achieve and maintain a platelet count greater than or equal to 50x109/L as necessary to reduce the risk for bleeding. Do not exceed a dose of 75 mg daily.
Adult and pediatric patients 6 years and older with ITP: Initiate Eltrombopag at a dose of 50 mg once daily, except in patients who are of Asian ancestry or who have mild to severe hepatic impairment. For patients of Asian ancestry with ITP, initiate Eltrombopag at a reduced dose of 25 mg once daily. For patients with ITP
and mild, moderate or severe hepatic impairment, initiate Eltrombopag at a reduced dose of 25 mg once daily. For patients of Asian ancestry with ITP and hepatic impairment, consider initiating Eltrombopag at a reduced dose of 12.5 mg once daily.
Pediatric patients with ITP aged 1 to 5 years: Initiate Eltrombopag at a dose of 25 mg once daily.
Chronic hepatitis C associated thrombocytopenia: Initiate Eltrombopag at a dose of 25 mg once daily. Adjust the dose of Eltrombopag in 25 mg increments every 2 weeks as necessary to achieve the target platelet count required to initiate antiviral therapy. Do not exceed a dose of 100 mg daily.
First line severe aplastic anemia: Initiate Eltrombopag once daily at 2.5 mg/kg (in pediatric patients aged 2 to 5 years old), 75 mg (pediatric patients aged 6 to 11 years old) or 150 mg for patients aged 12 years and older for 6 months concurrently with standard immunosuppressive therapy. For patients of Asian ancestry or those with mild, moderate or severe hepatic impairment, decrease the initial dose by 50%. Modify the dose regimen of Eltrombopag based on platelet counts, ALT or AST elevations and thromboembolic events.
Refractory severe aplastic anemia: Initiate Eltrombopag at 50 mg once daily. Hematologic response requires dose titration, generally up to 150 mg and may take up to 16 weeks after starting Eltrombopag. For patients of Asian ancestry or those with mild, moderate, or severe hepatic impairment, initiate Eltrombopag at a reduced dose of 25 mg once daily. Adjust the dose of Eltrombopag in 50 mg increments every 2 weeks as necessary to achieve the target platelet count greater than or equal to 50 x 109/L as necessary. Do not exceed a dose of 150 mg per day.
