Promacta (Eltrombopag) for Chronic Immune Thrombocytopenia
Promacta (eltrombopag) is indicated for adult and pediatric patients ≥6 years with persistent or chronic ITP who have had insufficient response to corticosteroids, immunoglobulins, or splenectomy, and should only be used when the degree of thrombocytopenia increases bleeding risk. 1
Patient Selection and Timing
Use eltrombopag for patients at risk of bleeding who relapse after splenectomy or have contraindications to splenectomy and have failed at least one other therapy (Grade 1B recommendation). 2
Eltrombopag may be considered for patients at bleeding risk who have failed one line of therapy (corticosteroids or IVIg) and have not undergone splenectomy (Grade 2C). 2
The American Society of Hematology recommends thrombopoietin receptor agonists like eltrombopag as they increase platelet production rather than reducing immune-mediated destruction, representing a unique mechanism that directly enhances bone marrow platelet production. 3
Dosing Protocol
Initial dosing:
- Start at 36 mg orally once daily for most adult and pediatric patients ≥6 years. 1
- Reduce to 18 mg once daily for patients of East/Southeast Asian ancestry. 1
- Reduce to 18 mg once daily for patients with any degree of hepatic impairment (Child-Pugh Class A, B, or C). 1
Dose titration:
- Use the lowest dose necessary to achieve and maintain platelet counts ≥50 × 10⁹/L to reduce bleeding risk—do not normalize platelet counts. 1
- Platelet counts typically increase within 1-2 weeks of starting treatment and decrease within 1-2 weeks after discontinuation. 1
Efficacy Data
In pivotal trials, 59-70% of patients receiving eltrombopag 50 mg daily achieved platelet response (≥50 × 10⁹/L) compared to 11-16% with placebo. 1, 4
The 6-month RAISE trial demonstrated 79% of eltrombopag-treated patients responded at least once during the study versus 28% on placebo (odds ratio 8.2, p<0.0001). 5
Response rates were similar regardless of splenectomy status. 1
59% of patients reduced concomitant ITP medications versus 32% on placebo (p=0.016). 5
Critical Safety Monitoring
Hepatotoxicity (Black Box Warning):
- Monitor liver function tests before starting, every 2 weeks during dose titration, then monthly. 1
- Discontinue if ALT increases to ≥3× upper limit of normal with direct bilirubin elevation or clinical symptoms. 1
Thrombocytopenia rebound:
- Worsened thrombocytopenia with hemorrhage can occur following discontinuation—monitor platelet counts weekly for 4 weeks after stopping. 1, 4
- In clinical trials, serious hemorrhages occurred in 5 patients following eltrombopag discontinuation. 4
Bone marrow reticulin:
- Increased bone marrow reticulin formation has been reported, though long-term studies show this is not associated with clinically relevant medullary abnormalities in most cases. 2, 4
Thromboembolism:
- Thromboembolic events occurred in 2% of eltrombopag-treated patients versus 0% on placebo in pivotal trials. 5
Contraindication
- Do not use eltrombopag in patients with myelodysplastic syndromes (MDS) as it is not indicated and may pose risks. 1
Long-Term Management
Long-term treatment (up to 3 years) has demonstrated sustained efficacy with median platelet counts maintained >50 × 10⁹/L throughout follow-up. 6
Bleeding episodes decreased from 63% at baseline to 21% after 2 weeks of treatment and remained below baseline. 6
Sustained responses after tapering/discontinuation can occur: in published series, 15-48% of patients maintained response off-treatment for median follow-up periods of 6-33 months. 2
Consider attempting discontinuation in patients who achieve stable platelet counts, though this should be done with close monitoring given rebound thrombocytopenia risk. 2