Immune Thrombocytopenic Purpura (ITP) Medication

Updated: Apr 22, 2018
  • Author: Craig M Kessler, MD, MACP; Chief Editor: Srikanth Nagalla, MBBS, MS, FACP  more...
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Medication

Medication Summary

The treatment of acute immune thrombocytopenic purpura (ITP) requires considerable individualization. [80] General approaches for children with acute ITP and adults with chronic ITP are discussed below.

Recommended general approach for children with acute immune thrombocytopenic purpura

For initial (induction) treatment, in patients with a platelet count of 20-30 × 109/L [20-30 × 103/µL] and/or mucocutaneous bleeding), one regimen is prednisone 4-8 mg/kg/d with the intent of a rapid and complete taper after 7-10 days or when the platelet count reaches 50 × 109/L (50 × 103/µL), whichever occurs first. In critical situations, an IV infusion of a corticosteroid may be preferable.

Second-line (maintenance) treatment is IV Rh immune globulin (IG), 75/µg/kg (off-label dose) for the Rh-positive patient or IVIG 1.0 g/kg for the Rh-negative patient. If the patient has clinically significant purpura or bleeding at presentation, consider infusing the first dose of IV RhIG or IVIG at the time of initial therapy with corticosteroids.

Repeat the infusions at 3- to 4-week intervals (maintenance) until a satisfactory platelet count is achieved. If the platelet count is not maintained after 3-4 infusions, the case might be refractory, and a different treatment should be considered. Conditions refractory to IV RhIG may respond to IVIG, and vice versa. If the patient's hemoglobulin level decreases to 8.0 g/dL during treatment with IV RhIG, temporarily switch to IVIG until the level recovers. In this situation, the patient's condition should not be considered refractory to IV RhIG.

Conventional third-line treatment is splenectomy. However, recognizing the life-long potential adverse effects of splenectomy and the promising reports of responses to rituximab, [81, 82] the authors consider a course of rituximab 375 mg/m2 per week for four doses (off-label indication) before splenectomy (which becomes fourth-line therapy). [83] Rituximab at a standard dose of 375 mg/m2 per week for 4 weeks appears to be safe and effective, allowing nearly 40% of patients with ITP to achieve a long-term response and splenectomy-sparing effect in one study. [84]

Recommended general approach for adults with chronic immune thrombocytopenic purpura

Adults whose disease is not controlled with a prednisone-induced increase in platelet count that is maintained by IV RhIG or IVIG and whose conditions do not respond to four weekly infusions of rituximab are candidates for splenectomy. After these serial experiences, such patients are likely to have had thrombocytopenia for at least 6 months and, therefore, are categorized as having chronic ITP. Eltrombopag or romiplostim offer potential maintenance of safe levels of platelet counts for adults who qualify by having ITP for at least 6 months and whose conditions are refractory to conventional medical management (prednisone, IV RhIG, IVIG, rituximab), and whose platelet count is not maintained in a satisfactory range after splenectomy. [85]

The treatment of chronic, refractory ITP may introduce risks of toxicity from medications that are comparable in severity to the risks of untreated thrombocytopenia. These treatments also may impact adversely on the patient's quality of life. [86]

Fostamatinib was approved by the FDA in April 2018 for thrombocytopenia in adults with chronic ITP who have had an insufficient response to a previous treatment. It is the first spleen tyrosine kinase (SYK) inhibitor approved in the U.S. Approval was based on the FIT clinical program (n=163), which included 2 randomized placebo-controlled Phase 3 trials and an open-label extension trial. [94]

For patients with chronic refractory ITP who have access to investigational programs, the authors encourage them to participate in controlled clinical trials to support the development of effective treatments for this category.

Thrombopoietin-receptor agonists

Most conventional treatments for ITP act by decreasing destruction of autoantibody-coated circulating platelets. In contrast, thrombopoietin mimetics increase platelet counts in persons with ITP by increasing the number of platelets produced and released by the bone marrow. Agents in this class include the thrombopoietin peptide mimetic romiplostim (Nplate) and the nonpeptide mimetic eltrombopag (Promacta). [87, 88]

Romiplostim was approved by the US Food and Drug Administration (FDA) in August 2008. It is a thrombopoiesis-stimulating protein Fc-peptide fusion protein ("peptibody") that increases platelet counts in patients with acute and chronic ITP without reports of significant toxicity. [89, 33, 90]

Eltrombopag is indicated for treatment of thrombocytopenia in patients with chronic ITP who have shown insufficient response to corticosteroids, immunoglobulins, or splenectomy. This drug was also approved by the FDA in 2008. [91, 92] In August 2015, the FDA expanded the indication for eltrombopag to include treatment of chronic ITP in patients 1 year of age and older who have not achieved an appropriate response with other medical therapy or splenectomy. [58]

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Corticosteroids

Class Summary

Corticosteroids are the treatment of choice for initial management of acute ITP. These agents increase the platelet count by decreasing splenic uptake of autoantibody-coated platelets and by decreasing synthesis of autoantibody. Dosages must be tapered after a safe platelet count is achieved, and the drug is replaced with IV RhIG or IVIG to avoid serious complications of long-term steroid use.

Prednisone (Deltasone, Orasone, Sterapred)

Oral corticosteroid that is used most frequently because of its relatively low cost, known adverse effects, and long-term clinical record. DOC for initial treatment of ITP in children and adults. For aggressive treatment, may be combined with IV RhIG or IVIG. In emergency, replace PO prednisone with IV methylprednisolone.

Methylprednisolone (Solu-Medrol)

DOC for the initial management of severe bleeding tendency in ITP. IV is recommended when the most rapid and reliable treatment of ITP is required. In this situation, combine with IV RhIG in qualified Rh(D)-positive patients or IVIG in Rh(D)-negative patients or unqualified Rh(D)-positive patients.

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Blood Products

Class Summary

Blood products are used to improve clinical and immunologic aspects of ITP. These products may decrease autoantibody production and increase solubilization and removal of immune complexes.

IV RhIG (WinRho SDF)

Specialized immunoglobulin product manufactured from pools of plasma from Rh(D)-negative persons and alloimmunized to D blood group antigen. Subjected to anion-exchange column chromatography to permit IV infusion and solvent-detergent treatment and nanofiltration to reduce infectivity by lipid-enveloped viruses. Induces immune RBC hemolysis in Rh(D)-positive recipients, decreasing function of mononuclear macrophages (reticuloendothelial blockade) and sparing immunoglobulin-coated platelets from splenic destruction.

IVIG (Gamimune, Gammagard, Sandoglobulin)

Large dose of 1 g/kg induces decreased function of mononuclear macrophages (reticuloendothelial blockade), sparing immunoglobulin-coated platelets from splenic destruction. Used with IV methylprednisolone to manage acute ITP in children. Decreased time to an increased platelet count compared with IV RhIG, but the difference does not appear to be clinically significant. Compared with IV RhIG, associated with more adverse effects, longer infusions, and increased cost, causing many hematologists to prefer IV RhIG as a supplement to corticosteroids, at least for Rh(D)-positive patients.

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Immunosuppressive Antimetabolites

Class Summary

Immunosuppressive antimetabolites are used in patients with ITP to reduce production of abnormal autoantibodies.

Azathioprine (Imuran)

May be effective in some patients with ITP whose conditions do not or no longer have response to corticosteroids, IV RhIG, or IVIG. May be used with prednisone to reduce dose of prednisone or as another PO medication to delay splenectomy.

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Synthetic Antineoplastic Drugs

Class Summary

Synthetic antineoplastic drugs are chemically related to nitrogen mustards. These agents inhibit cell growth and proliferation.

Cyclophosphamide (Cytoxan)

May be useful in some patients whose conditions do not or no longer have a response to corticosteroids, IV RhIG, IVIG, or splenectomy. Induces less of a decrease in platelet count than other immunosuppressive alkylating agents.

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Androgens

Class Summary

The steroidogenic properties of androgens may modulate the immune system.

Danazol (Danocrine)

May impair the clearance of immunoglobulin-coated platelets and decreases autoantibody production. Increased platelet counts in 40-50% of patients, particularly postmenopausal women.

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Monoclonal Antibodies

Class Summary

Monoclonal antibodies are chimeric murine-human monoclonal antibodies directed against CD20 on B lymphocytes.

Rituximab (Rituxan)

Chimeric monoclonal antibody directed against the CD20 antigen on the surface of normal and malignant B lymphocytes. Antibody is IgG kappa immunoglobulin with murine light- and heavy-chain variable sequences and human constant region sequences.

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Thrombopoietin-Receptor Agonists

Class Summary

These new agents directly stimulate production of platelets by the bone marrow. [33]

Romiplostim (Nplate)

An Fc-peptide fusion protein (peptibody) that increases platelet production through binding and activation of the thrombopoietin (TPO) receptor, a mechanism similar to endogenous TPO. Indicated for chronic immune (idiopathic) thrombocytopenic purpura in patients who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy.

Eltrombopag (Promacta)

Oral thrombopoietin (TPO) receptor agonist. Interacts with transmembrane domain of human TPO receptor and induces megakaryocyte proliferation and differentiation from bone marrow progenitor cells. Indicated for thrombocytopenia associated with chronic idiopathic thrombocytopenic purpura in patients experiencing inadequate response to corticosteroids, immunoglobulins, or splenectomy. Not for use to normalize platelet counts, but used when clinical condition increases bleeding risk.

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SYK Inhibitors

Class Summary

Fostamatinib, is a first-in-class spleen tyrosine kinase (SYK) inhibitor indicated for chronic IPT in adults.

Fostamatinib (Tavalisse)

Fostamatinib is a spleen tyrosine kinase (SYK) inhibitor. The major active metabolite of fostamatinib (ie, R406) inhibits signal transduction of Fc-activating receptors and B-cell receptor, thereby reducing antibody-mediated destruction of platelets. It is indicated for thrombocytopenia in patients with chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment.

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