NPLATE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for NPLATE (NPLATE).
Thrombopoietin receptor agonist that binds to and activates the thrombopoietin receptor (c-Mpl), stimulating megakaryocyte proliferation and differentiation, leading to increased platelet production.
| Metabolism | Primarily metabolized via the reticuloendothelial system (catabolism); not extensively metabolized by cytochrome P450 enzymes. |
| Excretion | Renal excretion is minimal (<5% as unchanged drug); metabolism is expected via proteolysis to small peptides and amino acids; no biliary/fecal data available. |
| Half-life | Terminal half-life is 1–2 days (median 1.4 days) after weekly SC dosing; supports weekly administration. |
| Protein binding | ~25% bound to plasma proteins (no specific binding proteins identified). |
| Volume of Distribution | Vd is approximately 0.1 L/kg (confined primarily to plasma volume). |
| Bioavailability | SC: Approximately 28% (range 20–36%) after 1 mcg/kg dose. |
| Onset of Action | SC: Platelet count increases begin within 5–9 days after first dose. |
| Duration of Action | Platelet counts decline to baseline within 2 weeks after discontinuation; sustained elevation requires continued weekly dosing. |
1 mcg/kg subcutaneously once weekly, based on actual body weight.
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment required for renal impairment. Not studied in end-stage renal disease. |
| Liver impairment | No dose adjustment recommended for hepatic impairment per Child-Pugh classification. |
| Pediatric use | Safety and efficacy not established in pediatric patients under 18 years. |
| Geriatric use | No specific dose adjustment required; use based on body weight. Monitor for increased sensitivity or adverse effects. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for NPLATE (NPLATE).
| Breastfeeding | It is unknown if romiplostim is excreted in human milk. In nursing rats, romiplostim was detected in milk at concentrations approximately 5% of maternal serum levels. The molecular weight (~59 kDa) suggests limited transfer into breast milk. Caution is advised; consider the developmental and health benefits of breastfeeding versus the mother's clinical need for Nplate. |
| Teratogenic Risk | Nplate (romiplostim) is a thrombopoietin receptor agonist. Animal studies (rats and rabbits) show no evidence of teratogenicity at exposures up to 11-14 times the human exposure. In pregnant women, data are insufficient to establish risk; however, because it is an Fc-fusion protein, minimal transfer across the placenta is expected in the first trimester, increasing in the second and third trimesters. Use only if maternal benefit outweighs potential fetal risk. No specific congenital anomalies have been reported in limited human cases. |
■ FDA Black Box Warning
Risk of progression to acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) in patients with myelodysplastic syndromes (MDS). NPLATE should not be used in patients with MDS.
| Serious Effects |
["Hypersensitivity to romiplostim or any excipients.","Use in patients with myelodysplastic syndromes (MDS) due to risk of progression to AML."]
| Precautions | ["Bone marrow fibrosis: Monitor for reticulin deposition and progression to marrow fibrosis.","Thrombotic/thromboembolic complications: Risk of thrombosis, especially in patients with known risk factors.","Worsened thrombocytopenia after discontinuation: May worsen thrombocytopenia; monitor closely.","Risk of hematologic malignancies: Potential risk of AML/MDS in patients with MDS; avoid use in MDS.","Laboratory monitoring: Monitor platelet counts, CBC, and peripheral blood smears."] |
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| Fetal Monitoring | Monitor maternal platelet count weekly during pregnancy to adjust dose to maintain platelet count above 50 x 10^9/L. Monitor for signs of thrombosis (e.g., pulmonary embolism, deep vein thrombosis). Fetal monitoring: consider serial ultrasounds for growth and amniotic fluid volume, as with any high-risk pregnancy. No specific fetal cardiac monitoring is required unless indicated by maternal condition. |
| Fertility Effects | Animal studies (rats) showed no adverse effects on male or female fertility at exposures up to 29 times the human exposure. In humans, no fertility studies have been conducted; however, based on the mechanism (stimulation of thrombopoiesis), significant fertility impairment is not expected. |