Nplate ® romiplostim

Important Safety Information

Serious adverse reactions associated with Nplate^® in clinical studies were bone marrow reticulin deposition and worsening thrombocytopenia after Nplate^® discontinuation.

Bone Marrow Reticulin Formation and Risk for Bone Marrow Fibrosis

• Nplate^® administration increases the risk for development or progression of reticulin fiber deposition within the bone marrow.
• In clinical studies, Nplate^® was discontinued in four of the 271 patients because of bone marrow reticulin deposition. Six additional patients had reticulin observed upon bone marrow biopsy. All 10 patients with bone marrow reticulin deposition had received Nplate^® doses ≥ 5 mcg/kg, and 6 received doses ≥ 10 mcg/kg.
• Progression to marrow fibrosis with cytopenias was not reported in the controlled clinical studies. In the open-label extension study, one patient with ITP and hemolytic anemia developed marrow fibrosis with collagen during Nplate^® therapy.
• Clinical studies have not excluded a risk of bone marrow fibrosis with cytopenias.
• Prior to initiation of Nplate^® examine the peripheral blood smear closely to establish a baseline level of cellular morphologic abnormalities. Following identification of a stable Nplate^® dose, examine peripheral blood smears and CBCs monthly for new or worsening morphological abnormalities (eg, teardrop and nucleated red blood cells, immature white blood cells) or cytopenia(s).
• If the patient develops new or worsening morphological abnormalities or cytopenia(s), discontinue treatment with Nplate^® and consider a bone marrow biopsy, including staining for fibrosis.

Worsened Thrombocytopenia After Cessation of Nplate^®

• Discontinuation of Nplate^® may result in thrombocytopenia of greater severity than was present prior to Nplate^® therapy. This worsened thrombocytopenia may increase the patient’s risk of bleeding, particularly if Nplate^® is discontinued while the patient is on anticoagulants or antiplatelet agents.
• 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 two weeks and consider alternative treatments for worsening thrombocytopenia, according to current treatment guidelines.

Thrombotic/Thromboembolic Complications

• Thrombotic/thromboembolic complications may result from excessive increases in platelet counts. Excessive doses of Nplate^® or medication errors that result in excessive Nplate^® doses may increase platelet counts to a level that produces thrombotic/thromboembolic complications. In controlled clinical studies, the incidence of thrombotic/thromboembolic complications was similar between Nplate^® and placebo.
• 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.

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^® or bone marrow fibrosis.
• 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.

Hematological Malignancies and Progression of Malignancy in Patients with a Pre-existing Hematological Malignancy or Myelodysplastic Syndrome (MDS)

• Nplate^® stimulation of the TPO receptor on the surface of hematopoietic cells may increase the risk for hematologic malignancies. In controlled clinical studies among patients with chronic ITP, the incidence of hematologic malignancy was low and similar between Nplate^® and placebo.
• In a separate single-arm clinical study of 44 patients with myelodysplastic syndromes (MDS), 11 patients were reported as having possible disease progression, among whom 4 patients had confirmation of acute myelogenous leukemia (AML) during follow-up.
• Nplate^® is not indicated for the treatment of thrombocytopenia due to MDS or any cause of thrombocytopenia other than chronic ITP.

Laboratory Monitoring

• Monitor CBCs, including platelet counts and peripheral blood smears, prior to initiation, throughout, and following discontinuation of Nplate^® therapy.
• Prior to the initiation of Nplate^®, examine the peripheral blood differential to establish the baseline extent of red and white blood cell abnormalities.
• Obtain CBCs, including platelet counts and peripheral blood smears, 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 2 weeks following discontinuation of Nplate^®.

Nplate^® Distribution Program

• Nplate^® is available only through a restricted distribution program called Nplate^® NEXUS (Network of Experts Understanding and Supporting Nplate^® and Patients) Program. Under the Nplate^® NEXUS Program, only prescribers and patients registered with the program are able to prescribe, administer, and receive Nplate^®. This program provides educational materials and a mechanism for the proper use of Nplate^®. To enroll in the Nplate^® NEXUS Program, call 1-877-NPLATE1 (1-877-675-2831).

General Safety

• 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%).
• As with all therapeutic proteins, patients may develop antibodies to the therapeutic protein.

Please see Prescribing Information and Medication Guide