Romiplostim (Monograph)

Brand name: Nplate
Drug class: Hematopoietic Agents
- Colony-stimulating Factors
- CSFs
VA class: BL400
CAS number: 267639-76-9

Medically reviewed by Drugs.com on Jul 15, 2024. Written by ASHP.

Introduction

Biosynthetic (recombinant DNA-derived) Fc-peptide fusion protein; thrombopoietin-receptor agonist (TPO-RA).

Uses for Romiplostim

Immune Thrombocytopenia

Treatment of thrombocytopenia in adults with immune thrombocytopenia (ITP; also known as idiopathic thrombocytopenic purpura) who have had an inadequate response to corticosteroids, immunoglobulins, or splenectomy; should be used only in patients in whom the degree of thrombocytopenia and clinical status increase bleeding risk.

Treatment of thrombocytopenia in pediatric patients ≥1 year of age with ITP for at least 6 months who have had an inadequate response to corticosteroids, immunoglobulins, or splenectomy; should be used only in patients in whom the degree of thrombocytopenia and clinical status increase bleeding risk.

Do not use to normalize platelet counts since excessive increases in platelet count may increase the risk of thromboembolic complications.

Not indicated for the treatment of thrombocytopenia associated with myelodysplastic syndrome or thrombocytopenia associated with any condition other than chronic ITP.

Thrombopoietin receptor agonists (TPO-RAs) are used as second-line therapy for treatment of ITP, generally following lack of platelet response with corticosteroids and/or IV immune globulin (IVIG). Corticosteroids remain the standard initial therapy for newly diagnosed patients with ITP, but should be used for a limited duration only because of their adverse effects. Individualize treatment decisions and consider comparative risks and benefits, and adverse effects of therapy.

Hematopoietic Syndrome of Acute Radiation Syndrome

Used to increase survival in adults and pediatric patients (including term neonates) who are acutely exposed to myelosuppressive doses of radiation.

Efficacy studies not conducted for ethical and feasibility reasons. FDA approval for this indication is based on efficacy studies in animals, platelet count effect in healthy human volunteers, and data supporting use in patients with ITP.

Romiplostim Dosage and Administration

General

Patient Monitoring

In patients with immune thrombocytopenia (ITP), monitor complete blood counts (CBCs), including platelet counts, weekly during the dose adjustment phase, and then monthly after establishment of a stable dosage; because of the potential for worsening thrombocytopenia following discontinuance of romiplostim, monitor CBCs, including platelet counts, weekly for at least 2 weeks following discontinuation of the drug.

Dispensing and Administration Precautions

Because injection volumes of the drug may be very small in patients with ITP, romiplostim should be administered using a syringe with 0.01 mL graduations.
Ensure that recommended preparation and administration instructions are followed to minimize medication errors (e.g., excessive dosage or underdosage).

Administration

Reconstitution

Romiplostim lyophilized powder is supplied in single-use vials containing 125 mcg, 250 mcg, or 500 mcg of the drug; overfill is contained in each vial to ensure accurate delivery of calculated dose.

Reconstitute lyophilized romiplostim with sterile water for injection. If the calculated dose is <23 mcg, further dilution with 0.9% sodium chloride injection is required to a reduced concentration that allows for low doses to be accurately calculated and consistently measured with a 0.01 mL graduated syringe. Do not reconstitute or dilute the drug with bacteriostatic water for injection, or dilute with bacteriostatic sodium chloride injection.

The following reconstitution directions are for calculated romiplostim doses ≥23 mcg:

Vial labeled as containing 125 mcg of romiplostim: reconstitute with 0.44 mL of sterile water for injection to provide a final concentration of 500 mcg/mL
Vial labeled as containing 250 mcg of romiplostim: reconstitute with 0.72 mL of sterile water for injection to provide a final concentration of 500 mcg/mL
Vial labeled as containing 500 mcg of romiplostim: reconstitute with 1.2 mL of sterile water for injection to provide a final concentration of 500 mcg/mL

The following reconstitution directions are for calculated romiplostim doses <23 mcg:

Vial labeled as containing 125 mcg of romiplostim: reconstitute with 0.44 mL of sterile water for injection and dilute with 1.38 mL of 0.9% sodium chloride injection to provide a final concentration of 125 mcg/mL
Vial labeled as containing 250 mcg of romiplostim: reconstitute with 0.72 mL of sterile water for injection and dilute with 2.25 mL of 0.9% sodium chloride injection to provide a final concentration of 125 mcg/mL
Vial labeled as containing 500 mcg of romiplostim: reconstitute with 1.2 mL of sterile water for injection and dilute with 3.75 mL of 0.9% sodium chloride injection to provide a final concentration of 125 mcg/mL

Gently swirl and invert the vial to facilitate dissolution, which generally takes <2 minutes; do not shake or vigorously agitate the vial.

Reconstitution of the lyophilized drug as directed provides a clear and colorless solution.

Do not pool doses from multiple vials and do not use more than one dose from each single-use vial; discard any unused portions of the solution.

Sub-Q Administration

Administer by sub-Q injection. Administer as a weekly sub-Q injection for the treatment of ITP or as a one-time sub-Q injection for the treatment of hematopoietic syndrome of acute radiation syndrome.

Dosage

Pediatric Patients

Immune Thrombocytopenia

Sub-Q

Pediatric patients ≥1 year of age: Initially, 1 mcg/kg weekly based on actual body weight. Adjust dosage based on platelet count monitoring and changes in body weight. Reassessment of body weight in pediatric patients is recommended every 12 weeks.

Adjust dosage at weekly intervals in increments of 1 mcg/kg (up to a maximum dosage of 10 mcg/kg weekly) until a platelet count ≥50,000/mm³ is achieved.

Reduce dosage by 1 mcg/kg weekly if platelet count is >200,000/mm³ and ≤400,000/mm³ for 2 consecutive weeks. Do not administer if platelet count is >400,000/mm³; assess the platelet count weekly and resume romiplostim at a dosage reduced by 1 mcg/kg weekly once the platelet count is <200,000/mm³. Discontinue romiplostim if, after 4 weeks of therapy at the maximum recommended dosage of 10 mcg/kg weekly, the platelet count has not increased to a level sufficient to avoid clinically important bleeding.

Hematopoietic Syndrome of Acute Radiation Syndrome

Sub-Q

Pediatric patients (including term neonates): 10 mcg/kg as a single sub-Q injection. Administer the dose as soon as possible after suspected or confirmed exposure to radiation levels >2 gray (Gy).

Administer the drug regardless of whether a 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.

Adults

Immune Thrombocytopenia

Sub-Q

Initially, 1 mcg/kg weekly based on actual body weight. Adjust dosage based on platelet count monitoring.

Adjust dosage at weekly intervals in increments of 1 mcg/kg (up to a maximum dosage of 10 mcg/kg weekly) until a platelet count of ≥50,000/mm³ is achieved.

Hematopoietic Syndrome of Acute Radiation Syndrome

Sub-Q

10 mcg/kg as a single sub-Q injection. Administer the dose as soon as possible after suspected or confirmed exposure to radiation levels >2 gray (Gy).

Administer the drug regardless of whether a CBC can be obtained.

Prescribing Limits

Adults

Immune Thrombocytopenia

Sub-Q

Maximum 10 mcg/kg weekly.

Special Populations

No special population dosage recommendations at this time.

Cautions for Romiplostim

Contraindications

None.

Warnings/Precautions

Risk of Progression of Myelodysplastic Syndromes to Acute Myeloid Leukemia

Romiplostim stimulates the TPO receptor present on the surface of hematopoietic cells; may increase the risk for a hematologic malignancy, especially in patients with myelodysplastic syndrome (MDS).

Do not use romiplostim to treat thrombocytopenia related to MDS or any cause of thrombocytopenia other than ITP.

Thrombosis or Thromboembolic Complications

Risk of thrombosis or a thromboembolic complication as a result of excessive increase in platelet count secondary to excessive dosages of romiplostim.

To minimize the risk, do not use romiplostim to normalize platelet counts and follow recommended dosage adjustment guidelines.

Loss of Response

In cases of hyporesponsiveness or failure to maintain a platelet response, consider performing an evaluation of possible causative factors (e.g., presence of neutralizing antibodies). Blood samples for detection of antibody formation can be sent to Amgen to determine if antibodies to either romiplostim or TPO are present.

Discontinue romiplostim if the platelet count does not increase sufficiently after 4 weeks of treatment at the highest recommended dosage of 10 mcg/kg weekly.

Immunogenicity

Binding antibodies to romiplostim and TPO reported, including anti-romiplostim neutralizing antibodies.

Specific Populations

Pregnancy

Available studies in humans are insufficient to inform a drug-associated risk if romiplostim is used during pregnancy. However, the drug may cause fetal harm based on animal studies.

Lactation

Not known whether romiplostim is distributed into human milk or whether the drug has any effects on breast-fed infants or on milk production; however, human immunoglobulin G antibody (IgG) is distributed into milk.

Advise women not to breast-feed while receiving the drug.

Pediatric Use

Safety and efficacy not established in pediatric patients <1 year of age with ITP.

Use of romiplostim in pediatric patients (including term neonates) acutely exposed to myelosuppressive doses of radiation is based on efficacy studies conducted in animals; studies in humans could not be conducted because of ethical and feasibility reasons.

Geriatric Use

No overall differences in safety and efficacy in geriatric patients ≥65 years of age relative to younger adults, but increased sensitivity cannot be ruled out.

Common Adverse Effects

Most common adverse reactions in adults receiving romiplostim in clinical studies (≥5% higher patient incidence than placebo) were arthralgia, dizziness, insomnia, myalgia, pain in extremity, abdominal pain, shoulder pain, dyspepsia, and paresthesia.

Most common adverse reactions in pediatric patients receiving romiplostim in clinical studies (≥25%) were contusion, upper respiratory tract infection, and oropharyngeal pain.

Drug Interactions

May be used with other drugs to treat ITP such as corticosteroids, danazol, azathioprine, immune globulin IV (IGIV), and Rh_o(D) immune globulin.

Romiplostim Pharmacokinetics

Absorption

Bioavailability

Peak serum concentrations attained approximately 7–50 hours (median: 14 hours) following sub-Q administration of romiplostim doses of 3–15 mcg/kg.

Distribution

Extent

Not known whether romiplostim is distributed into milk.

Elimination

Elimination Route

Elimination of the drug is partly dependent on the TPO receptor on platelets. High platelet counts are associated with low serum romiplostim concentrations.

Half-life

Approximately 1–34 days (median: 3.5 days).

Stability

Storage

Parenteral

Powder for Injection

Unopened vials: 2–8°C; do not freeze. Store vials in original carton to protect from light. If needed, may store unopened vials in the original carton at room temperature (up to 25°C) for a single period of up to 30 days. Once stored at room temperature, do not place back in the refrigerator. If not used within the 30 days, discard.

Reconstituted solutions that have not been further diluted: Store in the original vial at room temperature (25°C) or refrigerated at 2–8°C for up to 24 hours after reconstitution. Alternatively, the reconstituted solution may be stored in a syringe at 25°C for up to 4 hours following reconstitution. Protect the drug from light and do not shake the vial.

Reconstituted solutions that have been further diluted: Store in a syringe at room temperature (25°C) or in the original vial refrigerated at 2–8°C for up to 4 hours prior to administration. Protect the drug from light and do not shake the vial.

Actions

Biosynthetic (recombinant DNA-derived) Fc-peptide fusion protein; thrombopoietin receptor agonist (TPO-RA). Produced by recombinant DNA technology in Escherichia coli.
Contains 2 identical single-chain subunits, each consisting of human IgG₁ Fc domain covalently linked at the C-terminus to a peptide containing 2 thrombopoietin receptor-binding domains.
Has no amino acid sequence homology to endogenous thrombopoietin.
Binds to the thrombopoietin receptor (also known as cMp1) and activates intracellular transcriptional pathways leading to increased platelet production.

Advice to Patients

Importance of providing patient with a copy of the manufacturer's patient information (medication guide) prior to each dose of romiplostim. Importance of carefully reading medication guide before initiating therapy and prior to receiving each dose.
Advise patients acutely exposed to myelosuppressive doses of radiation that efficacy studies 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.
Importance of understanding that the goal of therapy in ITP is to achieve and maintain a platelet count of ≥50,000/mm³ to reduce the risk of bleeding, not to normalize platelet counts.
Risk of worsening thrombocytopenia with possible bleeding following discontinuance of romiplostim.
Advise patients that romiplostim may increase the risk of reticulin fiber formation in bone marrow which may improve upon discontinuance of therapy.
Risk of thrombosis or thromboembolism.
Risk of progression of underlying MDS or hematologic malignancy.
Risk of adverse events associated with long-term administration not fully known.
Importance of avoiding situations or drug therapies that may increase risk of bleeding.
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and herbal supplements, as well as any concomitant illnesses.
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.
Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.