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