References
1. Data on file, Amgen Inc; Thousand Oaks, Calif.
2. Bussel JB, Kuter D, Pullarkat V, et al. Safety and efficacy of long-term treatment with romiplostim in thrombocytopenic patients with chronic ITP. Blood. 2009;113:2161-2171.
3. Kuter DJ, Bussel JB, Lyons RM, et al. Efficacy of romiplostim in patients with chronic immune thrombocytopenic purpura: a double-blind randomised controlled trial. Lancet. 2008;371:395-403.
4. Kuter DJ, Bussel JB, Newland A, et al. Long-term efficacy and safety of romiplostim treatment of adult patients with chronic immune thrombocytopenia (ITP): a final report from an open-label extension study. Blood. 2010;116:Abstract 68. Data on file, Amgen;[Presented at 52nd American Society of Hematology Annual Meeting and Exposition; Orlando, FL; December 4-7, 2010].
5. Kuter DJ, Rummel M, Boccia R, et al. Romiplostim or standard of care in patients with immune thrombocytopenia. N Engl J Med. 2010;363:1889-1899. Online Supplementary Appendix. http://www.nejm.org. Accessed May 17, 2011.
6. Nplate® (romiplostim) prescribing information, Amgen.v5 Issue Date:12/2011.
7. Cines DB, Bussel JB. How I treat idiopathic thrombocytopenic purpura (ITP). Blood. 2005;106:2244-2251.
8. Rodeghiero F, Ruggeri M. Is splenectomy still the gold standard for the treatment of chronic ITP? Am J Hematol. 2008;83:91.
9. 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;113:2386-2393.
10. Provan D, Stasi R, Newland AC, et al. International consensus report on the investigation and management of primary immune thrombocytopenia. Blood. 2010;115:168-186.
11. Stasi R, Amadori S, Osborn J, Newland AC, Provan D. Long-term outcome of otherwise healthy individuals with incidentally discovered borderline thrombocytopenia. PLoS Med. 2006;3:e24.
12. Cines DB, Blanchette VS. Immune thrombocytopenic purpura. N Engl J Med. 2002;346:995-1008.
13. Emmons RV, Reid DM, Cohen RL, et al. Human thrombopoietin levels are high when thrombocytopenia is due to megakaryocyte deficiency and low when due to increased platelet destruction. Blood.1996;87:4068-4071.
14. Gernsheimer T. Pathophysiology and thrombokinetics in autoimmune thrombocytopenia. Blood Rev. 2002;16:7-8.
15. Houwerzijl EJ, Blom NR, van der Want JL, et al. Ultrastructural study shows morphologic features of apoptosis and para-apoptosis in megakaryocytes from patients with idiopathic thrombocytopenic purpura. Blood. 2004;103:500-506.
16. Nichol JL. Endogenous TPO (eTPO) levels in health and disease: possible clues for therapeutic intervention. Stem Cells.1998;16(suppl 2):165-175.
17. Neunert C, Lim W, Crowther M, Cohen A, Solberg L, Jr, Crowther MA. The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood. 2011;117:4190-4207.
18. Cines DB, McMillan R. Management of adult idiopathic thrombocytopenic purpura. Ann Rev Med. 2005;56:425-442.
19. Kaushansky K. The molecular mechanisms that control thrombopoiesis. J Clin Invest. 2005;115:3339-3347.
20. Braendstrup P, Bjerrum OW, Nielsen OJ, et al. Rituximab chimeric anti-CD20 monoclonal antibody treatment for adult refractory idiopathic thrombocytopenic purpura. Am J Hematol. 2005;78:275-280.
21. Solu-Medrol® (methylprednisolone sodium succinate) prescribing information. Pfizer, Inc. Revision Date: 10/2009.
22. FDA.gov. CDER drug and biologic approvals for calendar year 2008. http://www.fda.gov/downloads/Drugs/
DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/DrugandBiologicApprovalReports/UCM200924.pdf. Accessed December 1, 2010.
23. Promacta® prescribing information, GlaxoSmithKline v2. Research Triangle Park, NC. Revision Date: 10/2009.
24. Bussel JB, Kuter DJ, Newland A, et al. Long-term efficacy and safety of romiplostim for the treatment of patients with chronic immune thrombocytopenia (ITP): 5-year update from an open-label extension study. Blood. 2009;114:abstract 681. Data on file, Amgen;[Presented at 51st American Society of Hematology Annual Meeting and Exposition, December 2009].
25. Gernsheimer TB, George JN, Aledort LM, et al. Evaluation of bleeding and thrombotic events during long-term use of romiplostim in patients with chronic immune thrombocytopenia (ITP). J Thromb Haemost. 2010;8:1372-1382.
26. Kuter DJ, Rummel MJ, Boccia R, et al. Comparison of splenectomy and treatment failure incidence in nonsplenectomized patients with immune thrombocytopenia (ITP) receiving romiplostim or medical standard of care: 1-year treatment and 6-month safety follow-up. Blood. 2009;114: Abstract 679. Data on file, Amgen;[Presented at 51st American Society of Hematology Annual Meeting and Exposition; New Orleans, LA; December 5-8, 2009].
27. Rummel M, Boccia R, Macik G, et al. Efficacy and safety of romiplostim versus medical standard of care as chronic therapy for nonsplenectomized patients with immune thrombocytopenia (ITP). Haematologica. 2009;94(suppl 2):425 Abstract 1059. Data on file, Amgen;[Presented at 14th Congress of the European Hematology Association; Berlin, Germany; June 7, 2009].
28. George JN, Buchanan GR. Platelet counts: how are they done and how useful are they? ITP Support Association Platelet Reprint Series: an American perspective; June 2004.
29. Autoantibodies precede disease in lupus patients [news release]. Bethesda, MD: NIH News, National Institutes of Health, US Department of Health and Human Services; November 5, 2003. http://www.nih.gov/news/pr/nov2003/niams-05.htm. Accessed February 18, 2011.
30. MedlinePlus Medical Encyclopedia Web site. http://www.nlm.nih.gov/medlineplus/encyclopedia.html. Accessed February 18, 2011.
31. Kidney and urologic diseases. National Kidney and Urologic Diseases Information Clearinghouse Web site. http://kidney.niddk.nih.gov. Accessed February 18, 2011.
32. Medical dictionary, medical terminology. Stedman’s Medical Dictionary Search Engine. http://www.medilexicon.com/medicaldictionary.php. Accessed February 18, 2011.
33. Merriam-Webster Online Dictionary. http://www.merriam-webster.com/dictionary. Accessed February 18, 2011.
34. Drachman JG, Kaushansky K. Dissecting the thrombopoietin receptor: functional elements of the Mpl cytoplasmic domain. Proc Natl Acad Sci U S A. 1997;94:2350-2355.
INDICATION
Nplate® is a thrombopoietin receptor agonist indicated for the treatment of thrombocytopenia in patients with chronic immune thrombocytopenia (ITP) who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy.
Nplate® is not indicated for the treatment of thrombocytopenia due to myelodysplastic syndrome (MDS) or any cause of thrombocytopenia other than chronic ITP. Nplate® should be used only in patients with ITP whose degree of thrombocytopenia and clinical condition increase the risk for bleeding. Nplate® should not be used in an attempt to normalize platelet counts.
Important Safety Information
Risk of Progression of Myelodysplastic Syndromes to Acute Myelogenous Leukemia
- In Nplate® clinical trials of patients with myelodysplastic syndromes (MDS) and severe thrombocytopenia, progression from MDS to acute myelogenous leukemia (AML) has been observed.
- Nplate® is not indicated for the treatment of thrombocytopenia due to MDS or any cause of thrombocytopenia other than chronic ITP.
Thrombotic/Thromboembolic Complications
- Thrombotic/thromboembolic complications may result from increases in platelet counts with Nplate® use. Portal vein thrombosis has been reported in patients with chronic liver disease receiving Nplate®. Nplate® should be used with caution in patients with ITP and chronic liver disease.
- To minimize the risk for thrombotic/thromboembolic complications, do not use Nplate® in an attempt to normalize platelet counts. Follow the dose adjustment guidelines to achieve and maintain a platelet count of ≥ 50 x 109/L.
Bone Marrow Reticulin Formation and Risk for Bone Marrow Fibrosis
- Nplate® administration may increase the risk for development or progression of reticulin fiber formation within the bone marrow. This formation may improve upon discontinuation of Nplate®.
- In a clinical study, one patient with ITP and hemolytic anemia developed marrow fibrosis with collagen during Nplate® therapy. Clinical studies are in progress to assess the risk of bone marrow fibrosis and clinical consequences with cytopenias.
- If new or worsening morphological abnormalities or cytopenia(s) occur, consider a bone marrow biopsy to include staining for fibrosis.
Worsened Thrombocytopenia after Cessation of Nplate®
- In clinical studies of patients with chronic ITP who had Nplate® discontinued, four of 57 patients developed thrombocytopenia of greater severity than was present prior to Nplate® therapy. This worsened thrombocytopenia resolved within 14 days.
- Following discontinuation of Nplate®, obtain weekly CBCs, including platelet counts, for at least 2 weeks and consider alternative treatments for worsening thrombocytopenia, according to current treatment guidelines.
Lack or Loss of Response to Nplate®
- Hyporesponsiveness or failure to maintain a platelet response with Nplate® should prompt a search for causative factors, including neutralizing antibodies to Nplate®.
- To detect antibody formation, submit blood samples to Amgen (1-800-772-6436). Amgen will assay these samples for antibodies to Nplate® and thrombopoietin (TPO).
- Discontinue Nplate® if the platelet count does not increase to a level sufficient to avoid clinically important bleeding after 4 weeks at the highest weekly dose of 10 mcg/kg.
Laboratory Monitoring
- Obtain CBCs, including platelet counts, weekly during the dose adjustment phase of Nplate® therapy and then monthly following establishment of a stable Nplate® dose.
- Obtain CBCs, including platelet counts, weekly for at least two weeks following discontinuation of Nplate®.
Adverse Reactions
- In the placebo-controlled studies, headache was the most commonly reported adverse drug reaction, occurring in 35% of patients receiving Nplate® and 32% of patients receiving placebo. Headaches were usually of mild or moderate severity.
- Most common adverse reactions (≥ 5% higher patient incidence in Nplate® versus placebo) were Arthralgia (26%, 20%), Dizziness (17%, 0%), Insomnia (16%, 7%), Myalgia (14%, 2%), Pain in Extremity (13%, 5%) , Abdominal Pain (11%, 0%), Shoulder Pain (8%, 0%), Dyspepsia (7%, 0%), and Paresthesia (6%, 0%).
Please see Prescribing Information and Medication Guide
Have questions about the Indication, Important Safety Information, Prescribing Information or Medication Guide?
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Clinical studies have evaluated the safety and efficacy of Nplate® treatment in adult patients with chronic ITP. Nplate® clinical trials have been conducted in both splenectomized and non-splenectomized patients, with some patients receiving Nplate® treatment for > 5 years.
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