, Volume 76, Issue 8, pp 869–878 | Cite as

Eltrombopag: A Review in Paediatric Chronic Immune Thrombocytopenia

  • Celeste B. BurnessEmail author
  • Gillian M. Keating
  • Karly P. Garnock-Jones
Adis Drug Evaluation


Eltrombopag (Promacta®; Revolade®) is an orally active thrombopoietin receptor agonist recently approved in the USA and the EU for use in paediatric patients aged ≥1 year with chronic immune thrombocytopenia (ITP) who have had an insufficient response or are refractory to other ITP treatments (e.g. corticosteroids, immunoglobulins or splenectomy). The efficacy of 7 or 13 weeks’ therapy with oral eltrombopag (up to 75 mg/day) was compared with that of placebo in patients aged 1–17 years with previously treated chronic ITP in randomized, double-blind, multicentre phase II and III trials (PETIT and PETIT-2). In these trials, the platelet response rate (primary endpoint of PETIT) and the sustained platelet response rate (primary endpoint of PETIT-2) were significantly higher with eltrombopag than with placebo. A clinical benefit was shown by a reduction in the need for rescue therapy with eltrombopag versus placebo in both trials and a reduction of clinically significant bleeding in PETIT. During longer-term therapy (open-label treatment period for ≥24 weeks), eltrombopag maintained platelet counts above 50 × 109/L in the majority of patients and approximately one-half of patients were able to reduce or discontinue concurrent ITP drugs. Eltrombopag was generally well tolerated. Current evidence suggests that eltrombopag is a valuable addition to the limited treatment options available for the management of chronic ITP in paediatric patients with an inadequate response to first-line therapies.


Breast Cancer Resistance Protein Romiplostim Eltrombopag Platelet Response Thrombopoietin Receptor Agonist 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



During the peer review process, the manufacturer of eltrombopag was also offered an opportunity to review this article. Changes resulting from comments received were made on the basis of scientific and editorial merit.

Compliance with Ethical Standards


The preparation of this review was not supported by any external funding.

Conflicts of interest

Celeste B. Burness, Gillian Keating and Karly P. Garnock-Jones are salaried employee of Adis/Springer, are responsible for the article content and declare no relevant conflicts of interest.


  1. 1.
    Rodeghiero F, Stasi R, Gernsheimer T, et al. Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children: report from an international working group. Blood. 2009;113(11):2386–93.CrossRefPubMedGoogle Scholar
  2. 2.
    Labarque V, Van Geet C. Clinical practice: immune thrombocytopenia in paediatrics. Eur J Pediatr. 2014;173(2):163–72.CrossRefPubMedGoogle Scholar
  3. 3.
    Neunert C, Lim W, Crowther M, et al. The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood. 2011;117(16):4190–207.CrossRefPubMedGoogle Scholar
  4. 4.
    Provan D, Stasi R, Newland AC, et al. International consensus report on the investigation and management of primary immune thrombocytopenia. Blood. 2010;115(2):168–86.CrossRefPubMedGoogle Scholar
  5. 5.
    Garnock-Jones KP. Eltrombopag: a review of its use in treatment-refractory chronic primary immune thrombocytopenia. Drugs. 2011;71(10):1333–53.CrossRefPubMedGoogle Scholar
  6. 6.
    GlaxoSmithKline. Promacta® (eltrombopag): US prescribing information. 2015. Accessed 17 Mar 2016.
  7. 7.
    European Medicines Agency. Revolade™ (eltrombopag): EU summary of product characteristics. 2016. Accessed 26 Apr 2016.
  8. 8.
    Burness CB. Eltrombopag: a review of its use in the treatment of thrombocytopenia in patients with chronic hepatitis C. Drugs. 2014;74(16):1961–71.CrossRefPubMedGoogle Scholar
  9. 9.
    McCormack PL. Eltrombopag: a review of its use in patients with severe aplastic anaemia. Drugs. 2015;75(5):525–31.CrossRefPubMedGoogle Scholar
  10. 10.
    Erickson-Miller CL, Delorme E, Tian SS, et al. Preclinical activity of eltrombopag (SB-497115), an oral, nonpeptide thrombopoietin receptor agonist. Stem Cells. 2009;27(2):424–30.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Jenkins JM, Williams D, Deng Y, et al. Phase 1 clinical study of eltrombopag, an oral, nonpeptide thrombopoietin receptor agonist. Blood. 2007;109(11):4739–41.CrossRefPubMedGoogle Scholar
  12. 12.
    Bussel JB, De Miguel PG, Despotovic JM. Eltrombopag for the treatment of children with persistent and chronic immune thrombocytopenia (PETIT): a randomised, multicentre, placebo-controlled study. Lancet Haematol. 2015;2(8):e315–25.CrossRefPubMedGoogle Scholar
  13. 13.
    Grainger JD, Locatelli F, Chotsampancharoen T, et al. Eltrombopag for children with chronic immune thrombocytopenia (PETIT2): a randomised, multicentre, placebo-controlled trial. Lancet. 2015;386:1649–58.CrossRefPubMedGoogle Scholar
  14. 14.
    Bussel JB, Cheng G, Saleh MN, et al. Eltrombopag for the treatment of chronic idiopathic thrombocytopenic purpura. N Engl J Med. 2007;357(22):2237–47.CrossRefPubMedGoogle Scholar
  15. 15.
    Erhardt JA, Erickson-Miller CL, Aivado M, et al. Comparative analyses of the small molecule thrombopoietin receptor agonist eltrombopag and thrombopoietin on in vitro platelet function. Exp Hematol. 2009;37(9):1030–7.CrossRefPubMedGoogle Scholar
  16. 16.
    Psaila B, Bussel JB, Linden MD, et al. In vivo effects of eltrombopag on platelet function in immune thrombocytopenia: no evidence of platelet activation. Blood. 2012;119(17):4066–72.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Matthys G, Park JW, McGuire S, et al. Eltrombopag does not affect cardiac repolarization: results from a definitive QTc study in healthy subjects. Br J Clin Pharmacol. 2010;70(1):24–33.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    FDA. Clinical pharmacology review. 2015. Accessed 17 Mar 2016.
  19. 19.
    Matthys G, Park JW, McGuire S, et al. Clinical pharmacokinetics, platelet response, and safety of eltrombopag at supratherapeutic doses of up to 200 mg once daily in healthy volunteers. J Clin Pharmacol. 2011;51(3):301–8.CrossRefPubMedGoogle Scholar
  20. 20.
    Wire MB, Bruce J, Gauvin J, et al. A randomized, open-label, 5-period, balanced crossover study to evaluate the relative bioavailability of eltrombopag powder for oral suspension (PfOS) and tablet formulations and the effect of a high-calcium meal on eltrombopag pharmacokinetics when administered with or 2 hours before or after PfOS. Clin Ther. 2012;34(3):699–709.CrossRefPubMedGoogle Scholar
  21. 21.
    Williams DD, Peng B, Bailey CK, et al. Effects of food and antacids on the pharmacokinetics of eltrombopag in healthy adult subjects: two single-dose, open-label, randomized-sequence, crossover studies. Clin Ther. 2009;31(4):764–76.CrossRefPubMedGoogle Scholar
  22. 22.
    Bussel JB, Grainger JD, de Miguel PG, et al. PETIT and PETIT 2: treatment with eltrombopag in 171 children with chronic immune thrombocytopenia (ITP) [abstract]. Blood. 2014;124(21):1450.Google Scholar
  23. 23.
    Cheng G, Saleh MN, Marcher C, et al. Eltrombopag for management of chronic immune thrombocytopenia (RAISE): a 6-month, randomised, phase 3 study. Lancet. 2011;377(9763):393–402.CrossRefPubMedGoogle Scholar
  24. 24.
    Grainger JD, Routledge DJM, Kruse A, et al. Thrombopoietin receptor agonists in paediatric ITP patients: long term follow up data in 34 patients [abstract]. Blood. 2014;124(21):4206.Google Scholar
  25. 25.
    Kuter DJ, Mufti GJ, Bain BJ, et al. Evaluation of bone marrow reticulin formation in chronic immune thrombocytopenia patients treated with romiplostim. Blood. 2009;114(18):3748–56.CrossRefPubMedGoogle Scholar
  26. 26.
    FDA. Clinical review: Promacta® (eltrombopag) tablets. 2015. Accessed 17 Mar 2016 2016.
  27. 27.
    McGuinn CE, Imahiyerobo A, Thompson M, et al. Safety and efficacy of eltrombopag at escalated doses up to 150 mg in patients with persistent and chronic immune thrombocytopenia (ITP) not responsive to 75 mg [abstract]. Blood. 2013;122(21):3559.Google Scholar
  28. 28.
    Ghanima W, Geyer JT, Lee CS, et al. Bone marrow fibrosis in 66 patients with immune thrombocytopenia treated with thrombopoietin-receptor agonists: a single-center, long-term follow-up. Haematologica. 2014;99(5):937–44.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Ghadaki B, Nazi I, Kelton JG, et al. Sustained remissions of immune thrombocytopenia associated with the use of thrombopoietin receptor agonists. Transfusion. 2013;53(11):2807–12.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Mahevas M, Fain O, Ebbo M, et al. The temporary use of thrombopoietin-receptor agonists may induce a prolonged remission in adult chronic immune thrombocytopenia. Results of a French observational study. Br J Haematol. 2014;165(6):865–9.CrossRefPubMedGoogle Scholar
  31. 31.
    Amgen Inc. Nplate® (romiplostim), for subcutaneous injection: US prescribing information. 2014. Accessed 17 Mar 2016.
  32. 32.
    European Medicines Agency. Nplate (romiplostim): EU summary of product characteristics. 2015. Accessed 17 Mar 2016.
  33. 33.
    Bussel JB, Buchanan GR, Nugent DJ, et al. A randomized, double-blind study of romiplostim to determine its safety and efficacy in children with immune thrombocytopenia. Blood. 2011;118(1):28–36.CrossRefPubMedGoogle Scholar
  34. 34.
    Elalfy MS, Abdelmaksoud AA, Eltonbary KY. Romiplostim in children with chronic refractory ITP: randomized placebo controlled study. Ann Hematol. 2011;90(11):1341–4.CrossRefPubMedGoogle Scholar
  35. 35.
    Gonzalez-Porras JR, Mingot-Castellano ME, Andrade MM, et al. Use of eltrombopag after romiplostim in primary immune thrombocytopenia. Br J Haematol. 2015;169(1):111–6.CrossRefPubMedGoogle Scholar
  36. 36.
    Mori M, Kato M, Koh K, et al. Successful switching from eltrombopag to romiplostim in a pediatric patient with refractory chronic ITP. Rinsho Ketsueki. 2015;56(5):511–3.PubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • Celeste B. Burness
    • 1
    Email author
  • Gillian M. Keating
    • 1
  • Karly P. Garnock-Jones
    • 1
  1. 1.SpringerAucklandNew Zealand

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