Eltrombopag

• Immune Thrombocytopenia (ITP)
• Chronic Hepatitis C Thrombocytopenia
• Severe Aplastic Anemia
• Low Platelet Count

Eltrombopag is a thrombopoietin receptor agonist used to increase platelet production in various conditions including chronic immune thrombocytopenia (ITP), chronic hepatitis C-associated thrombocytopenia, and severe aplastic anemia. This oral medication stimulates megakaryocyte growth and differentiation.

Mechanism of Action

Eltrombopag is a small molecule, non-peptide thrombopoietin receptor (TpoR/c-MPL) agonist. It binds to the transmembrane domain of the TpoR, distinct from the binding site of endogenous thrombopoietin (TPO), and activates intracellular signaling pathways (JAK/STAT, MAPK) that promote megakaryocyte proliferation and differentiation from bone marrow progenitor cells. This leads to increased platelet production. Unlike recombinant TPO, eltrombopag does not compete with endogenous TPO and may have additive effects. In aplastic anemia, eltrombopag may also stimulate hematopoietic stem cells through direct and indirect mechanisms.

Available Formulations

Eltrombopag is available as film-coated tablets (12.5 mg, 25 mg, 50 mg, 75 mg) and as a powder for oral suspension (12.5 mg and 25 mg packets). The medication should be taken on an empty stomach (1 hour before or 2 hours after a meal). Food, especially dairy products and calcium-fortified foods, significantly reduces absorption. Metal cation-containing products should be separated by at least 4 hours.

Medical Uses

Eltrombopag is FDA-approved for chronic immune thrombocytopenia (ITP) in adults and pediatric patients 1 year and older with insufficient response to corticosteroids, immunoglobulins, or splenectomy; thrombocytopenia in patients with chronic hepatitis C to allow initiation and maintenance of interferon-based therapy; and severe aplastic anemia in patients with insufficient response to immunosuppressive therapy. It is also approved as first-line treatment for severe aplastic anemia in combination with standard immunosuppressive therapy.

Dosing Guidelines

For ITP in adults, start at 50 mg once daily (25 mg for East Asian patients), adjusting dose to achieve target platelet count (≥50,000/µL); maximum dose is 75 mg daily. For hepatitis C-associated thrombocytopenia, start at 25 mg daily, titrating to target platelet count needed for antiviral therapy. For severe aplastic anemia, doses up to 150 mg daily are used. Dose adjustments are based on platelet response. East Asian patients may have higher drug exposure and should start at reduced doses.

Important Safety Information

Eltrombopag carries a boxed warning for hepatotoxicity, including severe and potentially life-threatening cases. Liver function tests should be monitored before and during therapy; dose reduction or discontinuation may be required. The medication may increase thrombotic/thromboembolic risk in patients with chronic liver disease. Eltrombopag is only available through a restricted distribution program (PROMACTA CARES) for hepatitis C patients. Cataracts have developed in rodent studies; regular ophthalmologic monitoring is recommended.

Drug Interactions

Polyvalent cation-containing products (antacids, calcium, iron, magnesium, aluminum, zinc, selenium) significantly reduce eltrombopag absorption; administer 4 hours apart. Eltrombopag inhibits OATP1B1 and BCRP transporters, potentially increasing levels of substrates (rosuvastatin, methotrexate, topotecan). CYP2C8 and CYP1A2 metabolize eltrombopag; lopinavir/ritonavir may reduce levels. Monitor closely when used with other drugs affecting hepatic transporters.

Special Populations

Eltrombopag may cause fetal harm based on animal data; women should use effective contraception during treatment. It is unknown whether eltrombopag is excreted in human breast milk; breastfeeding is not recommended. Safety and efficacy have been established in pediatric patients 1 year and older for ITP. Elderly patients do not require dose adjustment but may be at increased thromboembolic risk. Dose reduction is not required for renal impairment. Reduce initial dose to 25 mg daily in patients with hepatic impairment (ITP) and avoid use in hepatitis C patients with hepatic decompensation.