Pharmacology Update

Eltrombopag Tablets (Promacta®)

By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD. Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente; and Assistant Clinical Professor of Medicine, University of California, San Francisco. Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA. Drs. Chan and Elliott report no financial relationship to this field of study.

Eltrombopag is a thrombopoietin (TPO) receptor agonist approved by the FDA for the treatment of thrombocytopenia. It is the second agent, after romiplostim, approved to stimulate the thrombopoietin receptor and the first in oral form. Eltrombopag is marketed by GlaxoSmithKline, Inc., as Promacta®.


Eltrombopag is indicated for the treatment of thrombocytopenia in patients with chronic immune (idiopathic) thrombocytopenia purpura who have had insufficient response to corticosteroids, immunoglobulin, or splenectomy.1


The recommended starting dose is 50 mg once daily taken on an empty stomach (1 hour before or 2 hours after a meal as food reduces the absorption). A 4-hour interval should be allowed between other medications, foods, or supplements containing cations (e.g., calcium, iron, zinc). The starting dose is 25 mg once daily for patients with East Asian ancestry or with moderate-to-severe hepatic insufficiency. The daily dose may be adjusted to achieve and maintain a platelet count of ≥ 50 x 109/L to prevent bleeding. The dose should not exceed 75 mg daily. Eltrombopag should be discontinued if the platelet count does not increase after 4 weeks of therapy or if the platelet count exceeds 200 x 109/L.1

Eltrombopag is available as 25 mg and 50 mg tablets.

Potential Advantages

Eltrombopag is effective orally. The other thrombopoietin receptor agonist, romiplostim, is given by subcutaneous injection. Approximately two-thirds of patients respond to eltrombopag.1

Potential Disadvantages

Eltrombopag increases the risk for development or progression of reticulin fiber deposits within the bone marrow. The risk of hematologic malignancies may be increased. Excessive production of platelets may lead to thrombotic or thromboembolic complications and discontinuation of the drug may result in worsening of thrombocytopenia. Eltrombopag may increase the risk of hepatotoxicity. Serum liver tests should be done at baseline, every 2 weeks during dose titration, and monthly after establishing a stable dose.1 Inducers and inhibitors of CYP1A2 and CYP2C8 may affect the plasma levels of eltrombopag. The drug is an inhibitor of the organic anion transporting polypeptide (substrates include atorvastatin, rosuvastatin, rifampin, methotrexate). Polyvalent cations reduce the absorption of eltrombopag. Other adverse events associated with eltrombopag include nausea, vomiting, menorrhagia, myalgia, paresthesia, cataract, dyspepsia, ecchymosis, increased ALT/AST, and conjunctival hemorrhage.1


Acting as a thrombopoietin receptor, eltrombopag stimulates megakaryocyte proliferation and differentiation, resulting in increased platelet production. Its efficacy and safety was shown in 2 randomized, double-blind, placebo-controlled studies.1,2 Study subjects had platelet counts of < 30 x 109/L and at least one prior therapy for ITP. In study 1, subjects (n = 114) were randomized to eltrombopag 50 mg daily or placebo at a 2:1 ratio. In study 2 (n = 117), subjects were randomized to 30 mg, 50 mg, 75 mg, or placebo at a 1:1:1:1 ratio. Subjects were treated for a maximum period of 6 weeks followed by 6 weeks off therapy. Seventy percent of patients had at least 2 prior ITP therapies (e.g., corticosteroids, immunoglobulin, rituximab, cytotoxic therapies, danazol, and azothiaprine) and 40% had splenectomies. The primary endpoint was achieving platelet count of ≥ 50 x 109/L. The response rates for the 50 mg dose were 59% (43/73) in study 1 and 70% (19/27) in study 2. Response was similar in subjects regardless of whether they had a splenectomy. Response was detected 1 week after initiation of therapy and maximum effect after 2 weeks of therapy. The incidences of bleeding during treatment were 17% for placebo and 7% for 50 mg of eltrombopag.2 Bleeding and platelet counts gradually return to baseline or near baseline during the 6-week follow-up. The drug is also being studied in thrombocytopenic patients with cirrhosis associated with hepatitis C.3

Clinical Implications

Idiopathic thrombocytopenia purpura is an acquired autoimmune disorder characterized by antibody-mediated destruction of platelets and impaired platelet production.4,5 The most serious consequence of the disease is risk of bleeding, particularly intracranial hemorrhage. Treatment has generally been targeted at the antibody-mediated platelet destruction with splenectomy, corticosteroids, IVIG, rituximab, and cytotoxic agents. It appears that the underlying immune defect may vary between patients and no single therapy is effective in all patients.6 There are now 2 TPO receptor agonists that target platelet production and provide options for patients who have not responded to corticosteroids, immunoglobulin, or splenectomy. Eltrombopag is available only through a restrictive distribution program, PROMACTA CARES. Prescribers, pharmacies, and patients must register with the program to prescribe, dispense, or receive the drug.


1. Promacta Product Information. Research Triangle Park, NC: GlaxoSmithKline; October 2008. Available at:

2. Bussel JB, et al. Eltrombopag for the treatment of chronic idiopathic thrombocytopenic purpura. N Engl J Med 2007;357:2237-2247.

3. McHutchison JG, et al. Eltrombopag for thrombocytopenia in patients with cirrhosis associated with hepatitis C. N Engl J Med 2007;357:2227-2236.

4. Stasi R, et al. Novel thrombopoietic agents: A review of their use in idiopathic thrombocytopenic purpura. Drugs 2008;68:901-912.

5. Tiu RV, Sekeres MA. The role of AMG-531 in the treatment of thrombocytopenia in idiopathic thrombocytopenic purpura and myelodysplastic syndromes. Expert Opin Biol Ther 2008;8:1021-1030.

6. Psaila B, Bussel JB. Immune thrombocytopenic purpura. Hematol Oncol Clin North Am 2007;21: 743-759, vii.