When is Promacta (eltrombopag) used in patients with immune thrombocytopenia (ITP)?

When to Use Promacta (Eltrombopag) in Immune Thrombocytopenia

Promacta (eltrombopag) should be initiated in adult and pediatric patients (≥6 years old) with persistent or chronic ITP who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy, and whose degree of thrombocytopenia increases their risk for bleeding. 1

Patient Selection Criteria

Disease Duration and Prior Treatment Requirements

• Use eltrombopag in patients with ITP lasting ≥3 months who are corticosteroid-dependent or have no response to corticosteroids 2
• The drug is FDA-approved for patients who have failed first-line therapies including corticosteroids, immunoglobulins, or splenectomy 1, 3
• Eltrombopag can be considered even in newly diagnosed steroid non-responsive ITP patients, with 80% showing response at 1 month and 76% sustaining response at 3 months 4

Platelet Count Thresholds

• Initiate treatment only when the degree of thrombocytopenia and clinical condition increase the risk for bleeding 1
• The goal is to achieve and maintain platelet counts ≥50 × 10⁹/L to reduce bleeding risk, not to normalize platelet counts 1
• Do not use eltrombopag to normalize platelet counts, as this increases thrombotic risk 1

Positioning in Treatment Algorithm

Second-Line Therapy Options

When patients fail first-line corticosteroids, three main second-line options exist: splenectomy, rituximab, and TPO-receptor agonists (TPO-RAs) 2

TPO-RAs like eltrombopag are increasingly preferred over splenectomy because:

• Splenectomy carries 3.02-fold increased risk of septicemia, 4.53-fold increased risk of pulmonary embolism, and 4.69-fold increased risk of non-Hodgkin lymphoma 2
• Splenectomy requires lifelong sepsis prevention management and has 20-30% relapse rates 2
• TPO-RAs demonstrate 70-80% response rates in clinical trials (85-95% in long-term studies) with responses typically seen within 1-2 weeks 2

Comparison with Other TPO-RAs

• When choosing between eltrombopag and romiplostim for patients with ITP ≥3 months who are corticosteroid-dependent or non-responsive, the American Society of Hematology guidelines do not provide preferential recommendation between the two agents 2
• Both agents are well-tolerated with long-term use and show similar efficacy profiles 2
• The choice between eltrombopag (oral) versus romiplostim (subcutaneous) depends primarily on patient preference for route of administration 2

Specific Clinical Scenarios

Pediatric Patients

• Eltrombopag is approved for pediatric patients ≥6 years old with chronic ITP who have had insufficient response to first-line therapies 1, 5
• In pediatric trials (PETIT and PETIT-2), eltrombopag significantly increased platelet response rates and reduced need for rescue therapy compared to placebo 5
• Approximately half of pediatric patients were able to reduce or discontinue concurrent ITP medications during long-term eltrombopag therapy 5

Patients with Hepatic Impairment

• For patients with mild, moderate, or severe hepatic impairment (Child-Pugh Class A, B, C), initiate at reduced dose of 18 mg once daily instead of standard 36 mg 1

East/Southeast Asian Ancestry

• For patients of East/Southeast Asian ancestry, initiate at reduced dose of 18 mg once daily due to pharmacokinetic differences 1

Critical Safety Considerations and Contraindications

Absolute Contraindications

• Eltrombopag is NOT indicated for patients with myelodysplastic syndromes (MDS) due to safety concerns 1

Major Safety Warnings

• Hepatotoxicity risk: Monitor liver function tests before starting, every 2 weeks during dose adjustment, and monthly once stable 1, 3
• Rebound thrombocytopenia with hemorrhage: Serious hemorrhages can occur following eltrombopag discontinuation—five patients experienced this in pivotal trials 3
• Bone marrow reticulin formation: Monitor for this complication with long-term use 3
• Thrombotic risk: Use caution in patients with thromboembolism risk factors, though the prothrombotic risk is still being fully established 6

Expected Response Timeline

• Platelet counts generally increase within 1-2 weeks of starting eltrombopag 1, 3
• Median platelet counts remain above 50 × 10⁹/L throughout long-term treatment 3, 7
• Bleeding episodes decrease significantly: from 63% at baseline to 21% after 2 weeks of treatment 7

Potential for Treatment-Free Remission

• Approximately 30% of patients achieve long-term (≥6 months) remission that is sustained off treatment, compared to only 9% spontaneous remission rate in untreated adults 2
• This disease-modifying activity may be linked to TPO-RA-mediated restoration of impaired regulatory T-cell function and immune tolerance 2
• For patients with stable responses for ≥6 months, tapering can be considered, though most patients require continuous therapy 2

Common Pitfalls to Avoid

• Do not delay switching from corticosteroids: Patients requiring on-demand corticosteroid administration after completing first-line induction should be promptly switched to second-line therapy rather than continuing prolonged corticosteroid exposure 2
• Do not continue initial corticosteroid treatment beyond 6-8 weeks before considering alternative therapy 2
• Do not use eltrombopag to achieve normal platelet counts: This increases thrombotic risk without additional clinical benefit 1
• Do not abruptly discontinue: Taper carefully to avoid rebound thrombocytopenia and hemorrhage 3