Pharmacology Update

Romiplostim Injection (Nplate™)

By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD . Dr. Elliot 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.

A new agent has been approved by the fda for the treatment of thrombocytopenia associated with chronic immune thrombocytopenia purpura (ITP). Romiplostim is a thombopoietin receptor agonist. It is marketed by Amgen, Inc., as Nplate™ and is only available through the Nplate™ NEXUS Program.


Romiplostim is indicated for the treatment of thrombocytopenia in patients with chronic immune (idiopathic) thrombocytopenia purpura who have insufficient response to corticosteroids, immunoglobulin, or splenectomy. It should be used in patients with increased risk of bleeding and not for normalizing platelet counts.1


The initial recommended dose is 1 mg/kg administered subcutaneously once weekly. The dose may be titrated by 1 mg/kg increments to achieve and maintain a platelet count of 50 ´ 109/L or greater as necessary to reduce the risk of bleeding. The dose should not exceed 10 mg/kg. Romplostim should not be used or continued if the platelet counts exceed 400 ´ 109/L or if platelet counts do not increase after 4 weeks at the maximum dose.1

Romiplostim is supplied as 250 mg and 500 mg single-use vials.

Potential Advantages

A majority of splenectomized (79%) and non-splenectomized (88%) patients showed an overall response to romiplostim.1,2

Potential Disadvantages

Romiplostim increases the risk for development or progression of reticulin fiber deposits within the bone marrow that may lead to marrow fibrosis and cytopenia. The risk of hematologic malignancies may be increased. Excessive production of platelets may lead to thrombotic or thromboembolic complications and discontinuation of romiplostin may result in worsening of thrombocytopenia.1 In clinical trials, common adverse events that occurred more frequently than placebo include dizziness (17% vs 0%), insomnia (16% vs 7%), myalgia (14% vs 2%), abdominal pain (11% vs 0%), and pain in extremities (13% vs 5%). The incidence of development of neutralizing antibodies to romiplostin is 5%.1


Romiplostin is a recombinant Fc-peptide fusion protein (peptibody). The peptide portion of this molecule binds to the thrombopoietin receptor resulting in stimulation, generally in a dose-related manner, of platelet production.1,3,4 The efficacy in ITP was shown in two similarly designed 24-week studies; one with splenectomized patients (n = 63) and the other in non-splenectomized patients (n = 63).1,2 The median baseline platelet counts were 19 ´ 109/L and 15 ´ 109/L, respectively. Prior treatment included corticosteroids, IVIG, rituximab, cytotoxic therapies, danazol, and azathioprine. Patients were allowed to continue these therapies if they were on a constant dosing schedule. Rescue therapies for bleeding, wet purpura, and immediate risk for hemorrhage included corticosteroids, IVIG, platelet infusion, and anti-D-immunoglobulin. Patients were randomized (2:1) to romiplostim starting at a weekly injection of 1 mg/kg or placebo and titrated to a target platelet count of 50 ´ 109/L to 200 ´ 109/L. The primary endpoint was durable response. This was defined as a weekly platelet count of 50 ´ 109/L or higher for 6 or more weeks of the last 8 weeks of therapy. Durable response was achieved in 38% of spenectomized patients and 61% of non-splenectomized patients. Lower body weight (< 70 kg) and no splenectomy were associated with increased rates of durable response. Transient response was any weekly platelet count 50 ´ 109/L or greater for any 4 weeks without a durable response. A majority of patients had an overall response (durable plus transient), 79% and 88%, respectively, vs 0% and 14% for placebo. Fifty percent of patients achieved the target by week 2-3, but overall the mean time to target is about 14 weeks. Platelet counts generally returned to levels less than 50 ´ 109/L after discontinuation of the drug with only 7 of 83 patients (8.4%) maintaining that level 12 weeks after discontinuation.2 About one-half of patients (52%) on romiplostim discontinued their ITP medication compared to 19% for the placebo group. More patients in the placebo group required rescue treatment (59.5% vs 21.7%) and had significant bleeding events (12% vs 7%). The drug was generally well tolerated. One patient assigned to romiplostim had increased baseline bone marrow reticulin and thrombosis occurred in 3 patients assigned to romiplostim.

Clinical Implications

Idiopathic thrombocytopenia purpura is an acquired autoimmune disorder characterized by antibody-mediated destruction of platelets but platelet production may also be affected.3,4 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. The potential of romiplostim to be used as a splenectomy-sparing agent is being investigated in a long-term study.5 Romiplostim provides a new mechanism of action by stimulating platelet production. It is only available through the Nplate™ NEXUS Program. Only prescribers and patients registered with the program can prescribe, administer, and receive product.


1. Nplate Product Information. Thousand Oaks, CA: Amgen, Inc.; August 2008.

2. Kuter DJ et al. Efficacy of romiplostim in patients with chronic immune thrombocytopenic purpura: A double-blind randomised controlled trial. Lancet 2008;371:395-403.

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

4. 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.

5. Clinical Trials Registry, National Institutes of Health. Available at: NCT00415532. Accessed Sept. 27, 2008.