Weycker D, Hatfield M, Grossman A, et al. Through this mechanism, romiplostim reduces the need for other treatments and decreases bleeding events in patients with thrombocytopenia. 2019 Jun 25;3(12):1907-1915. doi: 10.1182/bloodadvances.2019000279. Romiplostim is a TPO-RA that has been used in adults with chronic ITP for more than 11 years. Xue E, Lawrence T, Gernsheimer TB, Milano F. Retrospective evaluation of the use of romiplostim after hematopoietic stem cell transplantation. Thromboembolic/thrombotic complications may occur due to increases in platelet counts with romiplostim use secondary to drug-induced thrombocytopenia, regardless of the underlying disease. Do not inject into an area that has scars or stretch marks or is tender, red, bruised, or hard. Nursing Central is an award-winning, complete mobile solution for nurses and students. Adverse Reactions/Side Effects CNS: dizziness, insomnia, headache. Avoid shaking. Limited data in pregnant women are insufficient to inform a drug-associated risk of adverse developmental outcomes. It is possible that the (single) Fc domain could contribute to the rate at which romiplostim results in a treatment-free response. Romiplostim is given by subcutaneous injection. informational and educational purposes only. Romiplostim has no noted moderate interactions with any other drugs. In addition, TPO alters hematopoietic stem cell lineage differentiation via metabolic regulation. Consult your doctor before breast-feeding. A comparative prospective observational study of children and adults with immune thrombocytopenia: 2-year follow-up, Managing thrombocytopenia associated with cancer chemotherapy. Compare formulary status to other drugs in the same class. See What Are Side Effects Associated with Using Romiplostim?. Find information on Romiplostim (Nplate) in Davis's Drug Guide including dosage, side effects, interactions, nursing implications, mechanism of action, half life, administration, and more. Eltrombopag maintains human hematopoietic stem and progenitor cells under inflammatory conditions mediated by IFN-gamma, NMR structural studies of interactions of a small, nonpeptidyl Tpo mimic with the thrombopoietin receptor extracellular juxtamembrane and transmembrane domains. Romiplostim (molecular weight 60 kDa) is a peptibody composed of four identical thrombopoietin peptides of 14 amino acids each that are chemically coupled by glycine spacer domains to the carboxy-terminus of the Fc carrier domain. Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature. Newland A, Caulier MT, Kappers-Klunne M, et al. Hematologic: Anemia. Ise M, Iizuka H, Kamoda Y, Hirao M, Kida M, Usuki K. Romiplostim is effective for eltrombopag-refractory aplastic anemia: results of a retrospective study. Most Newland A, Lee EJ, McDonald V, Bussel JB. 995 - Domiciliary Nursing Management for Patients Affected By Multiple Myeloma during Covid-19 Pandemia in the Viterbo Home Care Unit: . Various pathways can be activated by the different substances. eCollection 2022. Accessibility A more recent phase 2 study explored the effect of eltrombopag in 23 evaluable patients with expanded types of inherited thrombocytopenia (ie, MYH9-RD, ankyrin repeat domain-containing protein 26 [ANKRD26]related thrombocytopenia, WiskottAldrich syndrome/X-linked thrombocytopenia, monoallelic Bernard-Soulier syndrome, or integrin beta-3 [ITGB3]related thrombocytopenia). National Institutes of Health. Nplate:- Do not freeze- Protect from light- See package insert for detailed storage information- Store in carton- Store unreconstituted product in refrigerator (36 to 46 degrees F), After discontinuation of romiplostim, thrombocytopenia and risk of bleeding may be more severe than that experienced prior to romiplostim therapy. MISSED DOSE: If you miss a dose, ask your doctor or pharmacist right away for a new dosing schedule. If the platelet count is more than 200,000/mm3 for 2 consecutive weeks, reduce the dose by 1 mcg/kg/week. Immune thrombocytopenic purpura (ITP) is a blood disorder. Romiplostim and eltrombopag induce platelet response after 1 to 2 weeks of treatment, whereas avatrombopag has a response onset of 3 to 5 days. [34386], Romiplostim may cause fetal harm when administered during human pregnancy. Antigens from phagocytosed platelets are thought to be presented by the MHCII to TCRs, stimulating autoreactive T cells. Bussel J, Kulasekararaj A, Cooper N, et al. Romiplostim is administered subcutaneously. Anemia Symptoms and Signs, Types, Treatment and Causes, Sarfaroj Khan, BHMS, PGD Health Operations. The site is secure. Supplement, April 2019, CAR T-Cell. Data from Broudy and Lin59 and Currao et al68 indicate that binding of romiplostim results in tyrosine phosphorylation and subsequent activation of Mp1, JAK2-STAT5, ERK1/2, and AKT downstream signaling pathways leading to gene transcription and increased megakaryocyte proliferation and differentiation. Adjust dose based on platelet count. Effect of thrombopoietin receptor agonists on the apoptotic profile of platelets in patients with chronic immune thrombocytopenia, Platelet survival and platelet production in idiopathic thrombocytopenic purpura (ITP) before and during treatment with corticosteroids. Although none of these indications have been approved yet in the United States, these studies highlight the versatility of romiplostim in thrombocytopenic conditions other than ITP. Erickson-Miller CL, Delorme E, Tian SS, et al. Lozano ML, Mingot-Castellano ME, Perera M, et al. Share cases and questions with Physicians on Medscape consult. Primary persistent thrombocytopenia is most prevalent with a cord blood transplant. Pathophysiology of immune thrombocytopenia.26 Production of antiplatelet autoantibodies appears to be a key event in the pathophysiology of ITP. Hosokawa K, Yamazaki H, Tanabe M, Imi T, Sugimori N, Nakao S. High-dose romiplostim accelerates hematologic recovery in patients with aplastic anemia refractory to eltrombopag. The approval for romiplostim by the US Food and Drug Administration (but not EMA) was recently extended to cover this early use.5 Studies have also shown romiplostim to be effective in improving platelet counts in various preclinical and clinical settings, including CIT, aplastic anemia, animal models of acute radiation syndrome, and liver disease. and clinical trials have the following requirements and considerations: Cosmetic and experimental services, which may include new and emerging technologies, often do not meet . To decrease the risk of overdose and its complications, ensure preparation and administration instructions are followed. No information is available on the excretion of romiplostim into breastmilk. Children aged 1 year and older who have had ITP for at least 6 months. 8.3 Nursing Mothers 8.4 Pediatric Use 8.5 Geriatric Use 8.6 Renal Impairment 8.7 Hepatic Impairment 10 OVERDOSAGE 11 DESCRIPTION 12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action 12.2 Pharmacodynamics 12.3 Pharmacokinetics 13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility 13.2 Animal Toxicology and/or Pharmacology You should not breastfeed while using Nplate. Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed. Risk and consequences of chemotherapy-induced thrombocytopenia in US clinical practice, Dose delays, dose reductions, and relative dose intensity in patients with cancer who received adjuvant or neoadjuvant chemotherapy in community oncology practices. It was estimated that nearly 10% of patients treated with chemotherapy experience clinically significant CIT during at least one cycle of their treatment.105 Current management for CIT includes platelet transfusions, which are reserved for patients with severe thrombocytopenia.104 Chemotherapy treatment delays and dose reductions are often used to manage CIT, which lead to reduced relative dose intensity and, consequently, reduced efficacy of the chemotherapy regimen.106,107 A recent study investigated the effects of the antifibrinolytic drug tranexamic acid in preventing therapy-induced thrombocytopenia in patients undergoing treatment for hematologic malignancies; however, early results indicate that prophylactic tranexamic acid had no effect on the incidence of bleeding.108 This suggests that a potential way to treat CIT is to increase platelet counts. Discontinue romiplostim if the platelet count does not increase to a level sufficient to avoid clinically significant bleeding after 4 weeks at the maximum dose of 10 mcg/kg/week. View all medicinal forms and pricing information. There can be variation in the licensing of different medicines containing the same drug. A retrospective evaluation of chemotherapy dose intensity and supportive care for early-stage breast cancer in a curative setting. 10 mcg/kg subcutaneously once, as soon as possible after suspected or confirmed exposure to radiation concentrations more than 2 gray. 1Department of Pediatrics, Division of Hematology, Weill Cornell Medicine, New York, NY, USA, 2Department of Medicine, Hematology Service, Memorial Sloan-Kettering Cancer Center, New York, NY, USA, 3Clinica Pediatrica Universit degli Studi di Milano Bicocca, Ospedale San Gerardo, Monza, Italy, 4Hammersmith Hospital, Imperial College, London, UK, 6Division of Hematology and Transfusion Medicine, Lund University, Lund, Sweden, 7Department of Pharmacology, University of Toronto, Toronto, ON, Canada. Kojima S, Matsuyama T, Kodera Y, Tahara T, Kato T. Measurement of endogenous plasma thrombopoietin in patients with acquired aplastic anaemia by a sensitive enzyme-linked immunosorbent assay, Endogenous TPO (eTPO) levels in health and disease: possible clues for therapeutic intervention, Efficacy and safety of romiplostim in patients with acquired aplastic anemia ineligible or refractory to immunosuppressive therapy: interim analysis of phase 2/3 clinical trial, Efficacy and safety of romiplostim in refractory aplastic anaemia: a phase II/III, multicentre, open-label study, Study of AMG531(Romiplostim) in patients with aplastic anemia (NCT03957694), Study of AMG531 (Romiplostim) in patients with aplastic anemia (NCT04095936). Through this mechanism, romiplostim reduces the need for other treatments and decreases bleeding events in patients with thrombocytopenia. This supplement to the Clinical Journal of Oncology Nursing features trailblazing work by oncology nurses and their interprofessional colleagues from across the country. Diverse functions of the thrombopoietin receptor agonist romiplostim rescue individuals exposed to lethal radiation, Mitigative effects of a combination of multiple pharmaceutical drugs on the survival of mice exposed to lethal ionizing radiation. Detection of anti-platelet antibodies in immune thrombocytopenia by flow cytometry. Reassess weight every 12 weeks. With 5 years of follow-up, 29 patients (20 in the romiplostim group; 9 in placebo) progressed to AML (HR 1.06, 95% CI 0.48 to 2.33). Production of antiplatelet autoantibodies appears to be a key event in the pathophysiology of ITP. Thrombopoietin Receptor Agonists: Eltrombopag and Romiplostim for the Treatment of Chronic Immune Thrombocytopenia Purpura April 2019 Clinical Journal of Oncology Nursing 23(2):212-216 There was a higher incidence of death in the romiplostim arm in the baseline low IPSS group (41.3% vs. 30.4%; HR 1.59, 95% CI 0.67 to 3.8). 12 In this phase 1/2 study, 22 children, with a diagnosis of ITP for 6 months and a platelet count <30 10 9 /L, were randomized to receive romiplostim or placebo. https://profreg.medscape.com/px/getpracticeprofile.do?method=getProfessionalProfile&urlCache=aHR0cHM6Ly9yZWZlcmVuY2UubWVkc2NhcGUuY29tL2RydWcvbnBsYXRlLXJvbWlwbG9zdGltLTM0MjE3Nw==, View explanations for tiers and It is more effective than third-generation antibiotics against both gram-positive and gram-negative bacteria. The presence of autoantibodies is not always associated with active disease.40,42 In these patients, cell-mediated immune mechanisms, such as CD8+ cells in bone marrow, might suppress megakaryocyte apoptosis, leading to impaired platelet production and thrombocytopenia.36,43,44 Platelets can present antigens to CD8+ cells, indicating that they may also participate in the initiation of acquired immune responses in addition to supporting and promoting acquired immune responses.45 This characteristic of platelets is thought to arise from megakaryocytes.46 Evidence also suggests a role for increased classical pathway complement activation in ITP.47, Platelet survival is controlled by an intrinsic apoptotic program. We also summarize the clinical evidence supporting its use in ITP and other disorders that involve thrombocytopenia, including chemotherapy-induced thrombocytopenia, aplastic anemia, acute radiation syndrome, perisurgical thrombocytopenia, post-HSCT thrombocytopenia, and liver disease. Loss of the terminal sialic acid residues triggers recognition and uptake by the Ashwell-Morell receptor.49,52 Uptake of the desialylated platelets stimulates JAK-STAT signaling and upregulation of TPO mRNA expression by the same pathway as interleukin (IL)-6 in hepatocytes, leading to increased serum TPO levels and subsequent increase in megakaryopoiesis and platelet biogenesis.5256, Romiplostim is a peptibody comprising four TPO-R binding domains (identified by screening mutagenesis peptide libraries57) with high affinity for the TPO-R (MPL) and one carrier Fc domain4,5,58,59 and has no sequence homology with endogenous TPO (Figure 3).4,58,60 Romiplostim binds to and activates the TPO-R on megakaryocyte precursors in bone marrow.58 It binds in the same manner as endogenous TPO and can displace TPO from its receptor.3,59 Romiplostim activates many of the same pathways as TPO, leading to sustained improvement of platelet counts with continued treatment in patients with ITP.6164 Preclinical and clinical data suggest that romiplostim also has immunomodulatory effects.65,66. Integrated analysis of long-term safety in patients with chronic immune thrombocytopaenia (ITP) treated with the thrombopoietin (TPO) receptor agonist romiplostim. Adverse Effects ( 1%) Body as a Whole: Bone pain, hyperuricemia, fever. Monitor CBC weekly during the dose adjustment phase and then monthly thereafter. In other studies, concurrent ITP medication use in adults was discontinued or decreased in responders with romiplostim use.63,74,75 No randomized trial comparing romiplostim with placebo identified a significantly higher rate of thromboembolic events in patients treated with romiplostim; however, in a pooled analysis of 14 studies that included adults and children treated with romiplostim for up to 5.4 years, the rate of thrombotic events was 5.5 per 100 patient-years for both the romiplostim and placebo groups.89 Therefore, the 5% rate of thrombotic/thromboembolic events in the long-term extension study of romiplostim being similar to the rate observed in an extension study of eltrombopag75,91 suggests that an incremental prothrombotic effect of treatment with thrombopoietic agents exists. Dilute the 125 mcg vial (total vial content, 230 mcg) with 0.44 mL of Sterile Water for Injection (final concentration of 500 mcg/mL). Increased platelet counts can reduce the need for platelet transfusions and decrease bleeding events in multiple conditions.6164 Romiplostim binds to and activates the TPO-R on megakaryocyte precursors,58 activating multiple cell-signaling pathways, leading to enhanced cell growth and cell viability, which results in increased platelet production.3,59,68 Although there are ample data on the use of romiplostim in adults and children with chronic ITP, evolving data on romiplostim in newly diagnosed patients with ITP shows its potential use as early treatment for adults who do not respond to corticosteroids. Tests were negative on retesting 3 and 6 months later. However, even in the patients who achieve these responses, an extension of survival has not been shown. There is less experience in children.171175 In particular, an Italian retrospective study recently reported on the use of eltrombopag in nine pediatric patients after HSCT; after a median treatment time of 36 days, eight of the nine patients (88%) achieved sustained platelet counts >50 109/L.173 In seven children with secondary failure of platelet recovery treated with romiplostim, six (86%) became transfusion-independent in the second week of treatment.174. They represent many of the institutions that are leading this period of rapid growth and discovery regarding CAR T-cell therapy and its implications for treatment. Talk with your doctor if this medication stops working well.Tell your doctor if your condition (bleeding/bruising) lasts or gets worse. Al-Samkari H, Parnes AD, Goodarzi K, Weitzman JI, Connors JM, Kuter DJ. AT A GLANCE ITP is primarily characterized by reduced platelet counts and classified based on disease duration. Giagounidis A, Mufti GJ, Fenaux P, et al. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first. Learn more Thrombopoietin Receptor Agonists in Children with Immune Thrombocytopenia: A New Therapeutic Era. Further exploration of these mechanisms in the function of peptibodies is warranted.67. For example, romiplostim activates the extracellular domain of the TPO-R, whereas eltrombopag and avatrombopag activate the transmembrane portion of the TPO-R (Figure 4),),33 which could lead to different levels of activity of the TPO-R and hence different responses within the stem cell and megakaryocyte compartments. Romiplostim in patients undergoing hematopoietic stem cell transplantation: results of a phase 1/2 multicenter trial, Use of thrombopoietin receptor agonists in prolonged thrombocytopenia after hematopoietic stem cell transplantation. Romiplostim displays dose-dependent increases in platelets. Prior to extending a contract, we must receive the following documents. Among patients in this retrospective study receiving only romiplostim (n=41) or eltrombopag (n=41), 95.1% in each group were not exposed to switching. numbness or tingling in your hands or feet; trouble sleeping; stomach pain, indigestion, nausea, vomiting, diarrhea; cough, wheezing, chest tightness, trouble breathing; stuffy nose, sneezing . Upon exogenous TPO stimulation, HSCs differentiate to megakaryocytes. Common side effects of Romiplostim include: bruising, headache, dizziness, joint pain, muscle weakness or tenderness, pain in the arms, legs, or shoulder, numbness or tingling in the hands or feet, trouble sleeping, stomach pain, indigestion, nausea, vomiting, diarrhea, Patients received romiplostim weekly, starting at 1 g/kg and to a maximum of 10 g/kg. This work was supported by Amgen Inc., Thousand Oaks, CA, USA. Conversely, TPO binds to MPL receptors on circulating platelets in the blood when platelet levels are high. Thrombopoietin is synthesized in the liver and, Pathophysiology of immune thrombocytopenia. Gerald Soff has received research support from Amgen, Dova Pharmaceuticals, and Janssen Scientific Affairs; has participated in advisory boards and received consultancy fees from Amgen, Anthos Therapeutics, Bayer Pharmaceuticals, Bristol Myers Squibb, Dova Pharmaceuticals, Hengrui (USA) Ltd, Janssen Scientific Affairs, Novartis, and Pfizer; and has received honoraria from Amgen and Bayer Pharmaceuticals. Eulenfeld R, Dittrich A, Khouri C, et al. PMC [34386], 1 mcg/kg/week subcutaneously initially; adjust dose based on platelet counts and changes in body weight. Thousand Oaks, CA: Amgen Inc.; 2019. This figure does not include. The response rate is significantly lower in patients with a decreased number of megakaryocytes before treatment.162 No large prospective definitive studies have yet been reported. After reconstitution, romiplostim is stable at room temperature (25 C) or under refrigeration (2-8 C) for up to 24 hours. MEDICAL ALERT: Your condition can cause complications in a medical emergency. Subsequently, the need for . A few pilot and retrospective studies have suggested that romiplostim may be effective for improving platelet counts after HSCT.163165 In two small patient series, response to romiplostim was shown following HSCT in two of three patients166 and in six of eight patients.167 In a larger series, 100% of 20 patients treated with romiplostim achieved platelet engraftment at a median of 45 days following umbilical cord blood transplant compared with 85% of historical controls.168.
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