Important Safety Information

Risk of Progression of Myelodysplastic Syndromes to Acute Myelogenous Leukemia

• In Nplate^® (romiplostim) 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 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^®.
• 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.

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 (1‑800‑772‑64361‑800‑772‑6436). 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.

Adverse Reactions

Adult ITP

• In the placebo-controlled trials of adult ITP patients, headache was the most commonly reported adverse drug reaction, occurring in 35% of patients receiving Nplate^® and 32% of patients receiving placebo. Adverse drug reactions in adults with a ≥ 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%).
• The safety profile of Nplate^® was similar across patients, regardless of ITP duration. The following adverse reactions (at least 5% incidence and at least 5% more frequent with Nplate^® compared with placebo or standard of care) occurred in Nplate^® patients with ITP duration up to 12 months: bronchitis, sinusitis, vomiting, arthralgia, myalgia, headache, dizziness, diarrhea, upper respiratory tract infection, cough, nausea and oropharyngeal pain. The adverse reaction of thrombocytosis occurred with an incidence of 2% in adults with ITP duration up to 12 months.

Pediatric ITP

• The most common adverse reactions experienced by ≥ 5% of patients receiving Nplate^® with ≥ 5% higher incidence in the Nplate^® arm across the two placebo-controlled trials were contusion (41%), upper respiratory tract infection (31%), oropharyngeal pain (25%), pyrexia (24%), diarrhea (20%), rash (15%), and upper abdominal pain (14%).
• In pediatric patients of age ≥ 1 year receiving Nplate^® for ITP, adverse reactions with an incidence of ≥ 25% in the two randomized trials were: contusion (41%), upper respiratory tract infection (31%), and oropharyngeal pain (25%).
• In a long-term, single arm, open label pediatric safety study, headache occurred in 78/203 patients (38%); the incidence rates of other adverse reactions were similar to those reported in the placebo-controlled studies.

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 trial, one patient with ITP and hemolytic anemia developed marrow fibrosis with collagen during Nplate^® therapy.

INDICATIONS

Nplate^® is a thrombopoietin receptor agonist indicated for the treatment of thrombocytopenia in adult patients with immune thrombocytopenia (ITP) who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy. Nplate^® is indicated for the treatment of thrombocytopenia in pediatric patients 1 year of age and older with ITP for at least 6 months 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 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.

Please see full Prescribing Information and Medication Guide.