Detailed View: Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER)
Clinical Trials Experience
Bone Marrow Reticulin Formation and Collagen 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 trial, one patient with ITP and hemolytic anemia developed marrow fibrosis with collagen during Nplate therapy. An open-label clinical trial prospectively evaluated changes in bone marrow reticulin formation and collagen fibrosis in adult patients with ITP treated with Nplate or a non-US approved romiplostim product. Patients were administered romiplostim by SC injection once weekly for up to 3 years. Based on cohort assignment at time of study enrollment, patients were evaluated for bone marrow reticulin and collagen at year 1 (cohort1), year 2 (cohort 2) or year 3 (cohort 3) in comparison to the baseline bone marrow at start of the trial. Patients were evaluated for bone marrow reticulin formation and collagen fibrosis using the modified Bauermeister grading scale. From the total of 169 patients enrolled in the 3 cohorts, 132 (78%) patients were evaluable for bone marrow collagen fibrosis, and 131 (78%) patients were evaluable for bone marrow reticulin formation. Two percent (2/132) of patients (both from cohort 3) developed grade 4 findings (presence of collagen). There was no detectable bone marrow collagen in one patient on repeat testing 12 weeks after discontinuation of romiplostim. Progression of bone marrow reticulin formation (increase greater than or equal to 2 grades or more) or an increase to Grade 4 (presence of collagen) was reported in 7% (9/131) of patients.
USE IN SPECIFIC POPULATIONS
- In rat and rabbit developmental toxicity studies, no evidence of fetal harm was observed at romiplostim doses up to 11 times (rats) and 82 times (rabbits) the maximum human dose (MHD) based on systemic exposure. In mice at doses 5 times the MHD, reductions in maternal body weight and increased postimplantation loss occurred. In a prenatal and postnatal development study in rats, at doses 11 times the MHD, there was an increase in perinatal pup mortality. Romiplostim crossed the placental barrier in rats and increased fetal platelet counts at clinically equivalent and higher doses. Women who become pregnant during Nplate treatment are encouraged to enroll in Amgen’s Pregnancy Surveillance Program. Patients or their physicians should call 1-800-77-AMGEN (1-800-772-6436) to enroll.
- hypersensitivity and angioedema
MEDICATION GUIDE (New)
- To promote informed risk-benefit decisions before initiating treatment and while patients are on treatment to ensure appropriate use of Nplate (romiplostim)
- To establish the long-term safety and safe use of Nplate (romiplostim) through periodic monitoring of all patients who receive Nplate (romiplostim) for changes in bone marrow reticulin formation and bone marrow fibrosis, worsened thrombocytopenia after cessation of Nplate, thrombotic/thromboembolic complications, hematological malignancies and progression of malignancy in patients with a pre-existing hematological malignancy or myelodysplastic syndrome (MDS), and medication errors associated with serious outcomes.