Eltrombopag

Drug Class

  • Thrombopoietin receptor agonist (TPO-RA)
  • Oral, small molecule → binds c-Mpl (TPO receptor) on megakaryocyte precursors → stimulates platelet production.

Indications (FDA/Health Canada approved)

  1. Chronic Immune Thrombocytopenia (ITP)
    • Adults & children ≥1 year with persistent/refractory ITP after failure of corticosteroids, IVIG, or splenectomy.
  2. Severe Aplastic Anemia (SAA)
    • Adults with insufficient response to immunosuppressive therapy.
    • Used first-line in combination with ATG + cyclosporine (per NIH data).
  3. Thrombocytopenia in HCV (U.S. approval withdrawn in 2023)
    • Previously for patients needing interferon-based therapy (less relevant now with DAAs).
  4. Investigational/Off-label:
    • MDS, AML (supportive therapy in trials).

Dosing (general ranges)

  • ITP:
    • Adults: start 50 mg PO once daily.
    • East Asian ancestry or hepatic impairment: start 25 mg daily.
    • Adjust every 2 weeks to maintain platelets 50–200 × 10⁹/L.
    • Max dose: 75 mg/day.
  • Severe Aplastic Anemia (SAA):
    • Start 150 mg PO daily (75 mg if East Asian ancestry).
    • Continue at least 6 months or until response.

Safety & Monitoring

  • Hepatotoxicity:
    • Monitor LFTs regularly.
    • Hold/reduce if ALT/AST ≥3× ULN with symptoms.
  • Thrombosis risk:
    • Avoid platelets >200–250 × 10⁹/L.
    • Risk ↑ in older patients, cancer, or prolonged exposure.
  • Cataracts:
    • Periodic eye exams recommended.
  • Bone marrow fibrosis:

Drug/Food Interactions

  • Chelation issue: absorption ↓ with polyvalent cations (Ca, Mg, Al, Fe, Zn).
    • Separate from antacids, dairy, supplements by ≥4 hours.
  • CYP1A2 and UGT1A1 substrate:
    • Caution with inhibitors/inducers (e.g., ciprofloxacin, fluvoxamine).
  • Food: Best taken on an empty stomach, 1 hour before or 2 hours after meals.

Key Oncology Pearls

  • SAA: Eltrombopag revolutionized treatment — improves response rates when combined with immunosuppressive therapy.
  • AML/MDS: Not standard of care, but under study; concerns about clonal evolution exist.
  • Monitoring: CBC weekly until stable, then monthly; LFTs q2 weeks × 3 months, then monthly.

Takeaway:

Eltrombopag is an oral thrombopoietin receptor agonist used mainly in ITP and aplastic anemia to raise platelets. Must monitor LFTs, platelet counts, thrombotic risk, and drug-food interactions carefully.