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 have resulted from increases in platelet counts with Nplate^® use in the ITP population, including deep vein thrombosis (1.4%), pulmonary embolism (1.2%) and myocardial infarction (0.8%). Other thrombotic events including transient ischemic attack have been reported. These events have occurred regardless of platelet counts. Portal vein thrombosis has been reported in patients both with and without 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^®.
• 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.