FDA APPROVES ELTROMBOPAG for Treatment of Thrombocytopenia in Patients with Chronic ITP

eltrombopag treatment of thrombocytopenia in pediatric patients 1 year and older with chronic immune (idiopathic) thrombocytopenia

On August 24, 2015, the U. S. Food and Drug Administration approved eltrombopag (Promacta,Novartis) for the treatment of thrombocytopenia in pediatric patients 1 year and older with chronic immune (idiopathic) thrombocytopenia (ITP) who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy.

Eltrombopag tablets contain eltrombopag olamine, a small molecule thrombopoietin (TPO) receptor agonist for oral administration. Eltrombopag interacts with the  transmembrane domain of the TPO receptor (also known as cMpl) leading to increased platelet production.

The molecular weight is 564.65 for eltrombopag  olamine and 442.5 for eltrombopag free acid. Eltrombopag olamine has the following structural  formula:

ELTROM

CLINICAL PHARMACOLOGY

Mechanism of Action

Eltrombopag is an orally bioavailable, small-molecule TPO-receptor agonist that interacts with the transmembrane domain of the human TPO-receptor and initiates signaling cascades that induce proliferation and differentiation from bone marrow progenitor cells.

PROMACTA is a thrombopoietin receptor agonist indicated for the treatment of:
 thrombocytopenia in adult and pediatric patients 1 year and older with chronic immune (idiopathic) thrombocytopenia (ITP) who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy.

 thrombocytopenia in patients with chronic hepatitis C to allow the initiation and maintenance of interferon-based therapy.
 patients with severe aplastic anemia who have had an insufficient response to immunosuppressive therapy.
Limitations of Use:
 PROMACTA should be used only in patients with ITP whose degree of thrombocytopenia and clinical condition increase the risk for bleeding.

 PROMACTA should be used only in patients with chronic hepatitis C whose degree of thrombocytopenia prevents the initiation of interferon-based therapy or limits the ability to maintain interferon-based therapy.

 Safety and efficacy have not been established in combination with direct-acting antiviral agents used without interferon for treatment of chronic hepatitis C infection.

DOSAGE FORMS  

 Tablets: 12.5 mg, 25 mg, 50 mg, 75 mg, and 100 mg

 For oral suspension: 25 mg.

WARNINGS & PRECAUTIONS 

 Hepatotoxicity: Monitor liver function before and during therapy.
 Thrombotic/Thromboembolic Complications: Portal vein thrombosis has been reported in patients with chronic liver disease receiving PROMACTA. Monitor platelet counts regularly.

ADRS
 In adult patients with ITP, the most common adverse reactions (greater than or equal to 5% and greater than placebo) were: nausea, diarrhea, upper respiratory tract infection, vomiting, increased ALT, myalgia, and urinary tract infection.
 In pediatric patients age 1 year and older with ITP, the most common adverse reactions (greater than or equal to 10% and greater than placebo) were upper respiratory tract infection, and nasopharyngitis.
 In patients with chronic hepatitis C-associated thrombocytopenia, the most common adverse reactions (greater than or equal to 10% and greater than placebo) were: anemia, pyrexia, fatigue, headache, nausea, diarrhea, decreased appetite, influenza-like illness, asthenia, insomnia, cough, pruritus, chills, myalgia, alopecia, and peripheral edema.
 In patients with severe aplastic anemia, the most common adverse reactions (greater than or equal to 20%) were: nausea, fatigue, cough, diarrhea, and headache.