Nplate

Q: What are the side effects of Nplate?

The following clinically significant adverse reactions are discussed in greater detail in other sections: Progression of Myelodysplastic Syndromes [see Warnings and Precautions ( 5.1 )] Thrombotic/Thromboembolic Complications [see Warnings and Precautions ( 5.2 )] Loss of Response to Nplate [see Warnings and Precautions ( 5.3 )] In adult patients, the most common adverse reactions (≥ 5% higher… See the full label for the complete list.

Q: Who makes Nplate?

Nplate is listed by 1 labeler in the FDA NDC directory, including Amgen, Inc.

Romiplostim · Injection, Powder, Lyophilized, For Solution · Subcutaneous

Prescription (Rx) Thrombopoietin Receptor Agonist

Uses

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. ( 1.1 ) 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. ( 1.1 ) Nplate is indicated to increase survival in adults and in pediatric patients (including term neonates) acutely exposed to myelosuppressive doses of radiation (Hematopoietic Syndrome of Acute Radiation Syndrome [HS-ARS]). ( 1.2 ) Limitations of Use: 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 increases the risk for bleeding. Nplate should not be used in an attempt to normalize platelet counts. ( 1 ) 1.1 Patients with Immune Thrombocytopenia (ITP) Nplate is indicated for the treatment of thrombocytopenia in: Adult patients with immune thrombocytopenia (ITP) who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy. 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. 1.2 Patients with Hematopoietic Syndrome of Acute Radiation Syndrome Nplate is indicated to increase survival in adults and in pediatric patients (including term neonates) acutely exposed to myelosuppressive doses of radiation [see Clinical Studies (14.3) ] . Limitations of Use: Nplate is not indicated for the treatment of thrombocytopenia due to myelodysplastic syndrome (MDS) or any cause of thrombocytopenia other than ITP [see Warnings and Precautions ( 5.1 )] . Nplate should be used only in patients with ITP whose degree of thrombocytopenia and clinical condition increases the risk for bleeding. Nplate should not be used in an attempt to normalize platelet counts [see Warnings and Precautions ( 5.2 )] .

Dosage and administration

Patients with Immune Thrombocytopenia (ITP) Recommended Initial Dose: 1 mcg/kg once weekly as a subcutaneous injection. Adjust dose based on platelet response. ( 2.1 ) Patients acutely exposed to myelosuppressive doses of radiation Recommended Dose: 10 mcg/kg administered once as a subcutaneous injection. Administer the dose as soon as possible after suspected or confirmed exposure to myelosuppressive doses of radiation. ( 2.2 ) See Full Prescribing Information for instructions on reconstitution, preparation, and administration. ( 2.3 ) Reconstitution and Dilution of Nplate Single Dose Vials 2.1 Patients with Immune Thrombocytopenia (ITP) Use the lowest dose of Nplate to achieve and maintain a platelet count ≥ 50 × 10 9 /L as necessary to reduce the risk for bleeding. Administer Nplate as a weekly subcutaneous injection with dose adjustments based upon the platelet count response. The prescribed Nplate dose may consist of a very small volume (e.g., 0.15 mL). Administer Nplate only with a syringe that contains 0.01 mL graduations. Discontinue Nplate if the platelet count does not increase to a level sufficient to avoid clinically important bleeding after 4 weeks of Nplate therapy at the maximum weekly dose of 10 mcg/kg [see Warnings and Precautions ( 5.3 )] . Obtain complete blood counts (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 2 weeks following discontinuation of Nplate. For Adult Patients with ITP The initial dose of Nplate is 1 mcg/kg. Actual body weight at initiation of treatment should always be used when calculating the initial dose. In adults, future dose adjustments are based on changes in platelet counts only. Adjust the weekly dose of Nplate by increments of 1 mcg/kg until the patient achieves a platelet count ≥ 50 × 10 9 /L as necessary to reduce the risk for bleeding; do not exceed a maximum weekly dose of 10 mcg/kg. In clinical studies, most adult patients who responded to Nplate achieved and maintained platelet counts ≥ 50 × 10 9 /L with a median dose of 2-3 mcg/kg. Adjust the dose as follows for adult patients: If the platelet count is < 50 × 10 9 /L, increase the dose by 1 mcg/kg. If platelet count is > 200 × 10 9 /L and ≤ 400 × 10 9 /L for 2 consecutive weeks, reduce the dose by 1 mcg/kg. If platelet count is > 400 × 10 9 /L, do not dose. Continue to assess the platelet count weekly. After the platelet count has fallen to < 200 × 10 9 /L, resume Nplate at a dose reduced by 1 mcg/kg. For Pediatric Patients with ITP The initial dose of Nplate is 1 mcg/kg. Actual body weight at initiation of treatment should always be used when calculating initial dose. In pediatric patients, future dose adjustments are based on changes in platelet counts and changes in body weight. Reassessment of body weight is recommended every 12 weeks. Adjust the weekly dose of Nplate by increments of 1 mcg/kg until the patient achieves a platelet count ≥ 50 × 10 9 /L as necessary to reduce the risk for bleeding; do not exceed a maximum weekly dose of 10 mcg/kg. In a pediatric placebo-controlled clinical study, the median of the most frequent dose of Nplate received by patients during weeks 17 through 24 was 5.5 mcg/kg. Adjust the dose as follows for pediatric patients: If the platelet count is < 50 × 10 9 /L, increase the dose by 1 mcg/kg. If platelet count is > 200 × 10 9 /L and ≤ 400 × 10 9 /L for 2 consecutive weeks, reduce the dose by 1 mcg/kg. If platelet count is > 400 × 10 9 /L, do not dose. Continue to assess the platelet count weekly. After the platelet count has fallen to < 200 × 10 9 /L, resume Nplate at a dose reduced by 1 mcg/kg. 2.2 Patients with Hematopoietic Syndrome of Acute Radiation Syndrome For Adult and Pediatric Patients (including term neonates) The recommended dose of Nplate is 10 mcg/kg administered once as a subcutaneous injection. Administer the dose as soon as possible after suspected or confirmed exposure to radiation levels greater than 2 gray (Gy). Administer Nplate regardless of whether a complete blood count (CBC) can be obtained. Estimate a patient's absorbed whole body radiation dose (i.e., level of radiation exposure) based on information from public health authorities, biodosimetry if available, or clinical findings such as time to onset of vomiting or lymphocyte depletion kinetics. 2.3 Preparation and Administration To mitigate against medication errors (both overdose and underdose), ensure that these preparation and administration instructions are followed. Use aseptic technique. Only administer subcutaneously [see Overdosage ( 10 )] . Nplate is supplied in single-dose vials as a sterile, preservative-free, white lyophilized powder that must be reconstituted as outlined in Table 1 and administered using a syringe with 0.01 mL graduations. Calculation of Patient Dose Multiply the patient’s weight (kg) by the prescribed dose to obtain the Calculated Patient Dose. Calculated Patient Dose (mcg) = Weight (kg) × Prescribed dose (mcg/kg) Reconstitution and Dilution of Nplate Single - Dose Vials Reconstitute Nplate with Sterile Water for Injection, USP. Do not reconstitute or dilute with Bacteriostatic Water for Injection, USP or dilute with Bacteriostatic Sodium Chloride Injection, USP. If the Calculated Patient Dose is less than 23 mcg, dilution with 0.9% Sodium Chloride Injection, USP is required to reduce the concentration of Nplate (see Table 1 ). This reduced concentration allows for low-doses to be accurately calculated, and consistently measured with a 0.01 mL graduated syringe. Table 1. Reconstitution and Dilution of Nplate Single-Dose Vials Calculated Patient Dose Strength Vial contains overfill to ensure delivery of labeled vial strength. Reconstitute with Sterile Water Add Sterile Water for Injection, USP directly to the vial.

Dosage forms and strengths

For injection: 125 mcg, 250 mcg or 500 mcg of Nplate as a sterile, lyophilized, solid white powder in single-dose vials. For injection: 125 mcg, 250 mcg or 500 mcg of romiplostim as a lyophilized powder in single-dose vials. ( 3 )

Contraindications

None. None ( 4 )

Warnings and precautions

In some patients with MDS, Nplate increases blast cell counts and increases the risk of progression to acute myelogenous leukemia. ( 5.1 ) Thrombotic/thromboembolic complications have resulted from increases in platelet counts with Nplate use. Portal vein thrombosis has been reported in patients with chronic liver disease receiving Nplate. ( 5.2 ) Severe thrombocytopenia may persist during Nplate treatment due to neutralizing antibodies or other causes. ( 5.3 ) 5.1 Risk of Progression of Myelodysplastic Syndromes to Acute Myelogenous Leukemia Progression from myelodysplastic syndromes (MDS) to acute myelogenous leukemia (AML) has been observed in adult clinical trials with Nplate. A randomized, double-blind, placebo-controlled trial enrolling adult patients with severe thrombocytopenia and International Prognostic Scoring System (IPSS) low or intermediate-1 risk MDS was terminated due to more cases of AML observed in the Nplate arm. This trial consisted of a 58-week study period with a 5-year long-term follow-up phase. The patients were randomized 2:1 to treatment with Nplate or placebo (167 Nplate, 83 placebo). During the 58-week study period, progression to AML occurred in 10 (6.0%) patients in the Nplate arm and 4 (4.8%) patients in the placebo arm (hazard ratio [95%CI] = 1.20 [0.38, 3.84]). Of the 250 patients, 210 (84.0%) entered the long-term follow-up phase of this study. With 5 years of follow-up, 29 (11.6%) patients showed progression to AML, including 20/168 (11.9%) patients in the Nplate arm versus 9/82 (11.0%) patients in the placebo arm (HR [95% CI] = 1.06 [0.48, 2.33]). The incidence of death (overall survival) was 55.7% (93/167) in the Nplate arm versus 54.2% (45/83) in the placebo arm (HR [95% CI] = 1.03 [0.72, 1.47]). In the baseline low IPSS group, there was a higher incidence of death in the Nplate arm [41.3% (19/46)] compared to the placebo arm [30.4% (7/23)] (HR [95% CI] = 1.59 [0.67, 3.80]). In a single-arm trial of Nplate given to 72 patients with thrombocytopenia-related MDS, 8 (11.1%) patients were reported as having possible disease progression, of which 3 (4.2%) had confirmation of AML during follow-up. In addition, in 3 (4.2%) patients, increased peripheral blood blast cell counts decreased to baseline after discontinuation of Nplate. Nplate is not indicated for the treatment of thrombocytopenia due to MDS or any cause of thrombocytopenia other than ITP. 5.2 Thrombotic/Thromboembolic Complications Thrombotic/thromboembolic complications have resulted from increases in platelet counts with Nplate use secondary to drug-induced thrombocytosis, regardless of the underlying disease. Thrombotic/ thromboembolic events including deep vein thrombosis (1.4%), pulmonary embolism (1.2%) and myocardial infarction (0.8%) have been observed with the use of Nplate in the ITP population. 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 with and without chronic liver disease receiving Nplate. In patients with ITP, to minimize the risk for thrombotic/thromboembolic complications, do not use Nplate in an attempt to normalize platelet counts. Follow the dose adjustment guidelines [see Dosage and Administration ( 2.1 )] . In the absence of myelosuppression induced by acute exposure to radiation, Nplate administration might cause excessive increases in platelet counts and may cause thrombotic and thromboembolic complications [see Clinical Pharmacology (12.2) ]. 5.3 Loss of Response to Nplate Hyporesponsiveness or failure to maintain a platelet response with Nplate may occur due to neutralizing antibodies or other causes [see Adverse Reactions ( 6.3 )] . 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.

Side effects

The following clinically significant adverse reactions are discussed in greater detail in other sections: Progression of Myelodysplastic Syndromes [see Warnings and Precautions ( 5.1 )] Thrombotic/Thromboembolic Complications [see Warnings and Precautions ( 5.2 )] Loss of Response to Nplate [see Warnings and Precautions ( 5.3 )] In adult patients, the most common adverse reactions (≥ 5% higher patient incidence in Nplate versus placebo) are arthralgia, dizziness, insomnia, myalgia, pain in extremity, abdominal pain, shoulder pain, dyspepsia, and paresthesia. Headache was the most commonly reported adverse reaction that did not occur at ≥ 5% higher patient incidence in Nplate versus placebo. ( 6.1 ) In pediatric patients, the most common adverse reactions (≥ 25%) are: contusion, upper respiratory tract infection, and oropharyngeal pain. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Amgen Inc. at 1-800-77-AMGEN (1-800-772-6436) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Adults The data described below reflect Nplate exposure to 271 adult patients with ITP, aged 18 to 88, of whom 62% were female. Nplate was studied in two randomized, placebo-controlled, double-blind studies that were identical in design, with the exception that Study 1 evaluated non-splenectomized patients with ITP and Study 2 evaluated splenectomized patients with ITP. Data are also reported from an open-label, single-arm study in which patients received Nplate over an extended period of time. Overall, Nplate was administered to 114 patients for at least 52 weeks and 53 patients for at least 96 weeks. 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. For those patients receiving Nplate, 14 (48%) of headaches were mild, 9 (31%) were moderate, and 6 (21%) were severe. Table 3 presents adverse drug reactions from Studies 1 and 2 with a ≥ 5% higher patient incidence in Nplate versus placebo. Table 3. Adverse Reactions Identified in Two Placebo-Controlled Studies Adverse Reactions by Body System Nplate (%) (n = 84) Placebo (%) (n = 41) Musculoskeletal and Connective Tissue Disorders Arthralgia 22 (26%) 8 (20%) Myalgia 12 (14%) 1 (2%) Pain in Extremity 11 (13%) 2 (5%) Shoulder Pain 7 (8%) 0 Nervous System Disorders Dizziness 14 (17%) 0 Paresthesia 5 (6%) 0 Psychiatric Disorders Insomnia 13 (16%) 3 (7%) Gastrointestinal Disorders Abdominal pain 9 (11%) 0 Dyspepsia 6 (7%) 0 MedDRA version 9 is used. Among 291 adult patients with ITP who received Nplate in the single-arm extension study, the incidence rates of the adverse reactions occurred in a pattern similar to those reported in the placebo-controlled clinical studies. 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. 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 (cohort 1), 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. Pediatric Patients The data described below reflect median exposure to Nplate of 168 days for 59 pediatric patients (aged 1 to 17 years) with ITP for at least 6 months, of whom 47.5% were female, across the randomized phase of two placebo-controlled trials. Table 4 presents the most common adverse reactions experienced by at least 5% of the pediatric patients (1 year and older) receiving Nplate across the two placebo-controlled trials with at least a 5% higher incidence in patients who received Nplate compared to those who received placebo. Table 4.

Drug interactions

Nplate may be used with other medical ITP therapies, such as corticosteroids, danazol, azathioprine, intravenous immunoglobulin (IVIG), and anti-D immunoglobulin [see Clinical Studies ( 14.1 )] .

Use in specific populations

Pregnancy: May cause fetal harm. ( 8.1 ) Lactation: Advise not to breastfeed. ( 8.2 ) 8.1 Pregnancy Risk Summary Based on findings from animal reproduction studies, Nplate may cause fetal harm when administered to a pregnant woman. Available data with Nplate use in pregnant women are insufficient to draw conclusions about any drug-associated risk for major birth defects, miscarriage, or adverse maternal or fetal outcomes. In animal reproduction and developmental toxicity studies, romiplostim crossed the placenta, and adverse fetal effects included thrombocytosis, postimplantation loss, and an increase in pup mortality (see Data ). The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Data Animal Data In rat and rabbit embryo-fetal development 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 (AUC). 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. 8.2 Lactation Risk Summary There is no information regarding the presence of romiplostim in human milk, the effects on the breastfed child, or the effects on milk production. Maternal IgG is known to be present in human milk. The effects of local gastrointestinal exposure and limited systemic exposure in the breastfed child to romiplostim are unknown. Due to the potential for serious adverse reactions in a breastfed child from Nplate, advise women not to breastfeed during treatment with Nplate. 8.4 Pediatric Use Safety and effectiveness of Nplate have been established in pediatric patients age 1 year and older with ITP for at least 6 months evaluated in two randomized, placebo-controlled studies. Long-term safety in the same population using Nplate for a median duration of 3 years was also evaluated in a single arm, open-label study [ see Adverse Reactions ( 6.1 ), Clinical Studies ( 14.2 ) ] . The pharmacokinetics of romiplostim have been evaluated in pediatric patients 1 year and older with ITP [ see Clinical Pharmacology ( 12.3 ) ] . See Dosage and Administration ( 2.1 ) for dosing recommendations for pediatric patients 1 year and older. The safety and efficacy of Nplate in pediatric patients younger than 1 year with ITP have not been established. Serum concentrations of romiplostim in pediatric patients with ITP were within the range observed in adult patients with ITP receiving the same dose range of romiplostim. The use of Nplate to increase survival in pediatric patients (including term neonates) acutely exposed to myelosuppressive doses of radiation is based on efficacy studies conducted in adult animals. Efficacy studies of Nplate could not be conducted in humans with acute radiation syndrome for ethical and feasibility reasons. A similar response to Nplate is expected in the pediatric and adult patients based on the mechanism of action of the drug and pharmacokinetics of Nplate in pediatric patients 1 year and older with ITP [see Dosage and Administration (2.2) and Clinical Pharmacology (12.3) ] . 8.5 Geriatric Use Of the 271 patients who received Nplate in ITP clinical studies, 55 (20%) were age 65 and over, and 27 (10%) were 75 and over. No overall differences in safety or efficacy have been observed between older and younger patients in the placebo-controlled studies, but greater sensitivity of some older individuals cannot be ruled out. In general, dose adjustment for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Pregnancy

8.1 Pregnancy Risk Summary Based on findings from animal reproduction studies, Nplate may cause fetal harm when administered to a pregnant woman. Available data with Nplate use in pregnant women are insufficient to draw conclusions about any drug-associated risk for major birth defects, miscarriage, or adverse maternal or fetal outcomes. In animal reproduction and developmental toxicity studies, romiplostim crossed the placenta, and adverse fetal effects included thrombocytosis, postimplantation loss, and an increase in pup mortality (see Data ). The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Data Animal Data In rat and rabbit embryo-fetal development 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 (AUC). 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.

Pediatric use

8.4 Pediatric Use Safety and effectiveness of Nplate have been established in pediatric patients age 1 year and older with ITP for at least 6 months evaluated in two randomized, placebo-controlled studies. Long-term safety in the same population using Nplate for a median duration of 3 years was also evaluated in a single arm, open-label study [ see Adverse Reactions ( 6.1 ), Clinical Studies ( 14.2 ) ] . The pharmacokinetics of romiplostim have been evaluated in pediatric patients 1 year and older with ITP [ see Clinical Pharmacology ( 12.3 ) ] . See Dosage and Administration ( 2.1 ) for dosing recommendations for pediatric patients 1 year and older. The safety and efficacy of Nplate in pediatric patients younger than 1 year with ITP have not been established. Serum concentrations of romiplostim in pediatric patients with ITP were within the range observed in adult patients with ITP receiving the same dose range of romiplostim. The use of Nplate to increase survival in pediatric patients (including term neonates) acutely exposed to myelosuppressive doses of radiation is based on efficacy studies conducted in adult animals. Efficacy studies of Nplate could not be conducted in humans with acute radiation syndrome for ethical and feasibility reasons. A similar response to Nplate is expected in the pediatric and adult patients based on the mechanism of action of the drug and pharmacokinetics of Nplate in pediatric patients 1 year and older with ITP [see Dosage and Administration (2.2) and Clinical Pharmacology (12.3) ] .

Geriatric use

8.5 Geriatric Use Of the 271 patients who received Nplate in ITP clinical studies, 55 (20%) were age 65 and over, and 27 (10%) were 75 and over. No overall differences in safety or efficacy have been observed between older and younger patients in the placebo-controlled studies, but greater sensitivity of some older individuals cannot be ruled out. In general, dose adjustment for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Overdosage

Overdoses due to medication errors have been reported in patients receiving Nplate. In the event of overdose, platelet counts may increase excessively and result in thrombotic/thromboembolic complications. In this case, discontinue Nplate and monitor platelet counts. Reinitiate treatment with Nplate in accordance with dosing and administration recommendations [see Dosage and Administration ( 2.1 , 2.3 )] .

Description

Romiplostim is a thrombopoietin receptor agonist (TPO-RA). Romiplostim, a member of the TPO mimetic class, is an Fc-peptide fusion protein (peptibody). The peptibody molecule contains two identical single-chain subunits, each consisting of human immunoglobulin IgG1 Fc domain, covalently linked at the C-terminus to a peptide containing two thrombopoietin receptor-binding domains. Romiplostim has no amino acid sequence homology to endogenous TPO. Romiplostim is produced by recombinant DNA technology in Escherichia coli (E . coli) . Nplate (romiplostim) for injection is supplied as a sterile, preservative-free, lyophilized, solid white powder for subcutaneous use. Nplate is supplied as either 125 mcg per vial, 250 mcg per vial or 500 mcg per vial of romiplostim and requires reconstitution with Sterile Water for Injection to obtain a concentration of 500 mcg/mL. Each single-dose 125 mcg vial of Nplate contains the following: 125 mcg of romiplostim, L-histidine (0.7 mg), mannitol (18 mg), polysorbate 20 (0.02 mg), sucrose (9 mg), and sufficient HCl to adjust the pH to a target of 5. Reconstitution with 0.44 mL of Sterile Water for Injection provides a resulting concentration of 125 mcg/0.25 mL. Each single-dose 250 mcg vial of Nplate contains the following: 250 mcg romiplostim, L-histidine (1.2 mg), mannitol (30 mg), polysorbate 20 (0.03 mg), sucrose (15 mg), and sufficient HCl to adjust the pH to a target of 5. Reconstitution with 0.72 mL of Sterile Water for Injection provides a resulting concentration of 250 mcg/0.5 mL. Each single-dose 500 mcg vial of Nplate contains the following: 500 mcg romiplostim, L-histidine (1.9 mg), mannitol (50 mg), polysorbate 20 (0.05 mg), sucrose (25 mg), and sufficient HCl to adjust the pH to a target of 5. Reconstitution with 1.2 mL of Sterile Water for Injection provides a resulting concentration of 500 mcg/mL.

Mechanism of action

12.1 Mechanism of Action Nplate increases platelet production through binding and activation of the TPO receptor, a mechanism analogous to endogenous TPO.

How supplied

Nplate (romiplostim) for injection is supplied as a sterile, preservative-free, solid white lyophilized powder in single-dose vials of 125 mcg (NDC-55513-223-01, NDC-55513-223-21), 250 mcg (NDC 55513-221-01, NDC 55513-221-21) and 500 mcg (NDC 55513-222-01, NDC 55513-222-21) of romiplostim. Store Nplate vials in the refrigerator at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light. Do not freeze. If needed, unopened Nplate vials may be stored in the original carton at room temperature up to a maximum of 25°C (77°F) for a single period of up to 30 days. The new expiration date must be written in the space provided on the carton. Once stored at room temperature, do not place back in the refrigerator. If not used within the 30 days, discard Nplate.

Patient information

Advise the patient to read the FDA-approved patient labeling ( Medication Guide ). Advise patients acutely exposed to myelosuppressive doses of radiation (Hematopoietic Syndrome of Acute Radiation Syndrome) that efficacy studies of Nplate for this indication could not be conducted in humans for ethical and feasibility reasons and that, therefore, approval of this use was based on efficacy studies conducted in animals [see Clinical Studies (14.3) ] . Inform patients of the following risks and considerations for Nplate: Nplate therapy is administered to achieve and maintain a platelet count ≥ 50 × 10 9 /L as necessary to reduce the risk for bleeding; Nplate is not used to normalize platelet counts. Following discontinuation of Nplate, thrombocytopenia and risk of bleeding may develop that is worse than that experienced prior to the Nplate therapy. Nplate therapy may increase the risk of reticulin fiber formation within the bone marrow. This formation may improve upon discontinuation. Detection of peripheral blood cell abnormalities may necessitate a bone marrow examination. Too much Nplate may result in excessive platelet counts and a risk for thrombotic/thromboembolic complications. Nplate stimulates certain bone marrow cells to make platelets and increases the risk of progression to acute myelogenous leukemia in patients with myelodysplastic syndromes. Platelet counts and CBCs must be performed weekly until a stable Nplate dose has been achieved; thereafter, platelet counts and CBCs must be performed monthly while taking Nplate. Patients must be closely monitored with weekly platelet counts and CBCs for at least 2 weeks following Nplate discontinuation. Even with Nplate therapy, patients should continue to avoid situations or medications that may increase the risk for bleeding. Pregnancy: Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to inform their prescriber of a known or suspected pregnancy [see Use in Specific Populations ( 8.1 )] . Lactation: Advise women not to breastfeed during treatment with Nplate [see Use in Specific Populations ( 8.2 )] . Nplate ® (romiplostim) Manufactured by: Amgen Inc. One Amgen Center Drive Thousand Oaks, California 91320-1799 U.S. License No. 1080 Patent: http://pat.amgen.com/nplate/ © 2008-2025 Amgen Inc. All rights reserved. www.nplate.com 1xxxxx V21

Label text from the FDA structured product label by Amgen, Inc (revised Jun 23, 2026). Long sections are shortened; the complete label is on DailyMed.

Active ingredients

Romiplostim in 3 products

Nplate NDC products (3)

NDC	Strength & form	Labeler	Type
55513-221	Romiplostim 250 ug/.5mL Injection, Powder, Lyophilized, For Solution	Amgen, Inc	BLA
55513-222	Romiplostim 500 ug/mL Injection, Powder, Lyophilized, For Solution	Amgen, Inc	BLA
55513-223	Romiplostim 125 ug/.25mL Injection, Powder, Lyophilized, For Solution	Amgen, Inc	BLA