RomiPLOStim

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution Reconstituted, Subcutaneous [preservative free]:

Nplate: 125 mcg (1 ea); 250 mcg (1 ea); 500 mcg (1 ea)

Pharmacology

Mechanism of Action

Romiplostim is a thrombopoietin (TPO) peptide mimetic that increases platelet counts in ITP by binding to and activating the human TPO receptor.

Pharmacokinetics/Pharmacodynamics

Absorption

SubQ: Slow (Wang 2004)

Onset of Action

Platelet count increase: SubQ: 4 to 9 days (Wang 2004); Peak platelet count increase: Days 12 to 16 (Wang 2004)

Time to Peak

SubQ: Median: 14 hours (range: 7 to 50 hours)

Duration of Action

Platelet counts return to baseline by day 28 (Wang 2004)

Half-Life Elimination

Median: 3.5 days (range: 1 to 34 days)

Use: Labeled Indications

Immune thrombocytopenia: Treatment of thrombocytopenia in adult patients with immune thrombocytopenia (ITP) who have had insufficient response to corticosteroids, immune globulin, or splenectomy; treatment of thrombocytopenia in pediatric patients ≥1 year of age with ITP for ≥6 months who have had insufficient response to corticosteroids, immune globulin, or splenectomy.

Limitations of use: Romiplostim should be used only when the degree of thrombocytopenia and clinical condition increase the risk for bleeding; romiplostim should not be used in attempt to normalize platelet counts; romiplostim is not indicated for the treatment of thrombocytopenia due to myelodysplastic syndrome or any cause of thrombocytopenia other than ITP.

Contraindications

There are no contraindications listed in the manufacturer's US labeling.

Canadian labeling: Hypersensitivity to romiplostim or any component of the formulation; known history of sensitivity or allergy to any E. coli-derived product.

Dosage and Administration

Dosing: Adult

Note: Use the lowest dose sufficient to maintain platelet count ≥50,000/mm³ as necessary to reduce the risk of bleeding. Do not use to normalize platelet counts.

Immune thrombocytopenia: SubQ: Initial: 1 mcg/kg once weekly (based on actual body weight); adjust dose by 1 mcg/kg/week increments to achieve platelet count ≥50,000/mm³ and to reduce the risk of bleeding; Maximum dose: 10 mcg/kg/week (median dose needed to achieve response in clinical trials: 2 mcg/kg).

Dosage adjustment recommendations:

Adjust dose based on platelet count response:

Platelet count <50,000/mm³: Increase weekly dose by 1 mcg/kg.

Platelet count >200,000/mm³ to ≤400,000/mm³ for 2 consecutive weeks: Reduce weekly dose by 1 mcg/kg.

Platelet count >400,000/mm³: Withhold dose; assess platelet count weekly; when platelet count <200,000/mm³, resume with the weekly dose reduced by 1 mcg/kg.

Discontinue if platelet count does not increase to a level sufficient to avoid clinically important bleeding after 4 weeks at the maximum recommended dose of 10 mcg/kg/week.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Note: Use the lowest dose sufficient to maintain platelet count ≥50,000/mm³ as necessary to reduce the risk of bleeding. Do not use to normalize platelet counts. Reassess body weight every 12 weeks.

Chronic immune thrombocytopenia (ITP): Note: Calculate dose using actual body weight. Children and Adolescents: SubQ: Initial: 1 mcg/kg/dose once weekly; adjust dose by 1 mcg/kg/week increments to achieve platelet count ≥50,000/mm³ and to reduce the risk of bleeding; maximum dose: 10 mcg/kg/week

Dosage adjustment recommendations:

Adjust dose based on platelet count response:

Platelet count <50,000/mm³: Increase weekly dose by 1 mcg/kg.

Platelet count >200,000/mm³ to ≤400,000/mm³ for 2 consecutive weeks: Reduce weekly dose by 1 mcg/kg.

Platelet count >400,000/mm³: Withhold dose; assess platelet count weekly; when platelet count <200,000/mm³, resume with the weekly dose reduced by 1 mcg/kg.

Discontinue if platelet count does not increase to a level sufficient to avoid clinically important bleeding after 4 weeks at the maximum recommended dose of 10 mcg/kg/week.

Reconstitution

Reconstitute with only preservative-free SWFI (add 0.44 mL to 125 mcg vial, 0.72 mL to 250 mcg vial, or 1.2 mL to 500 mcg vial) to a concentration of 500 mcg/mL (due to overfill). Do not use bacteriostatic water for injection. Gently invert vial and swirl; do not shake. Usually dissolves within 2 minutes. If calculated dose is <23 mcg, additional dilution (after initial reconstitution with SWFI) with 0.9% sodium chloride (NS) is required (add 1.38 mL NS to 125 mcg vial, 2.25 mL NS to 250 mcg vial, or 3.75 mL NS to 500 mcg vial); final concentration will be 125 mcg/mL (due to overfill). Do not pool unused portions from vials; do not administer more than one dose from a vial.

Administration

SubQ: Administer subcutaneously only. Administration volume may be small; use appropriate syringe (with graduations to 0.01 mL) for administration. Verify calculations, final concentration, and volume drawn up for administration. Do not pool unused portions from vials; do not administer more than one dose from a vial.

Dietary Considerations

Some products may contain sucrose.

Storage

Store intact vials at 2°C to 8°C (36°F to 46°F); do not freeze. Protect from light. Store in original carton until use. If needed, unopened 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. Discard if not used within 30 days. Reconstituted solution (with SWFI) that has not been further diluted may be stored in the original vial at room temperature of 25°C (77°F) or refrigerated at 2°C to 8°C (36°F to 46°F) for up to 24 hours following reconstitution. Reconstituted solution (with SWFI) may be stored in a syringe at room temperature of 25°C (77°F) for a maximum of 4 hours following reconstitution. Protect reconstituted solution from light; do not shake. Solution diluted for infusion with 0.9% sodium chloride (NS) may be stored in a syringe at room temperature of 25°C (77°F) or in the original vial refrigerated at 2°C to 8°C (36°F to 46°F) for no longer than 4 hours prior to administration; protect from light; do not shake. Discard any unused portion.

Drug Interactions

There are no known significant interactions.

Adverse Reactions

Note: Incidences reported are for adult population unless otherwise noted.

>10%:

Central nervous system: Headache (35%), dizziness (17%), insomnia (16%)

Dermatologic: Skin rash (children and adolescents: 15%)

Gastrointestinal: Diarrhea (children and adolescents: 20%), upper abdominal pain (children and adolescents: 14%), abdominal pain (11%)

Hematologic & oncologic: Bruise (children and adolescents: 41%), myeloid leukemia (acute; 4% to 12%)

Neuromuscular & skeletal: Arthralgia (26%), myalgia (14%), limb pain (13%)

Respiratory: Upper respiratory tract infection (children and adolescents: 31%), oropharyngeal pain (children and adolescents: 25%)

Miscellaneous: Fever (children and adolescents: 24%)

1% to 10%:

Cardiovascular: Peripheral edema (children and adolescents: 7%)

Central nervous system: Paresthesia (6%)

Dermatologic: Urticaria (children and adolescents: 5%)

Gastrointestinal: Dyspepsia (7%), gastroenteritis (children and adolescents: 5%), nausea (≥5%), vomiting (≥5%)

Hematologic & oncologic: Purpuric disease (children and adolescents: 7%), thrombocythemia (2%)

Immunologic: Antibody formation (children, adults, and adolescents: 6% to 7%; neutralizing: 3% to 7%)

Infection: Infection (ear; children and adolescents: 5%)

Neuromuscular & skeletal: Shoulder pain (8%)

Respiratory: Bronchitis (≥5%), cough (≥5%), sinusitis (children and adolescents: 5%)

Frequency not defined: Hematologic & oncologic: Myelofibrosis (bone marrow reticulin formation/deposition)

<1%, postmarketing, and/or case reports: Angioedema, erythromelalgia, hypersensitivity reaction, portal vein, thrombosis

Warnings/Precautions

Concerns related to adverse effects:

• Bone marrow reticulin: May increase the risk for bone marrow reticulin fiber formation; this formation may improve upon discontinuation of therapy.
• Concomitant ITP medications: May be used in combination with other therapies for ITP, including corticosteroids, danazol, azathioprine, immune globulin, or Rho(D) immune globulin. Reduce dose of or discontinue ITP medications when platelet count ≥50,000/mm³.
• Error prevention: To prevent overdose or underdose, use caution when calculating dose and appropriate volume for administration (volume may be very small; administer with syringe that allows for 0.01 mL graduations).
• Hyporesponsiveness: Lack of response or failure to maintain platelet response should trigger investigation in to causative factors, including neutralizing antibodies to romiplostim.
• Malignancy: Progression from existing myelodysplastic syndrome (MDS) to acute myeloid leukemia (AML) has been observed in clinical trials studying romiplostim for severe thrombocytopenia associated with MDS (not an approved indication); a higher percentage of patients receiving romiplostim experienced transformation to AML (compared to placebo). An increase in the percentage of circulating myeloblasts in peripheral blood counts was also noted (both in patients who progressed to AML and in those who did not); blast cells decreased to baseline after discontinuation in some patients.
• Thromboembolism: Thromboembolism or thrombotic complications may occur with increased platelet counts. Follow dosage adjustment recommendations to minimize the risk for thrombotic or thromboembolic complications. Portal vein thrombosis has been observed in patients with chronic liver disease receiving romiplostim.

Monitoring Parameters

CBC with differential and platelets at baseline, weekly during dosage adjustment phase of treatment, then monthly, and weekly for at least 2 weeks following discontinuation or completion of treatment

Evaluate for neutralizing antibodies in patients with inadequate response (blood samples may be submitted to the manufacturer for assay [1-800-772-6436]).

Pregnancy

Pregnancy Considerations

Based on findings from animal reproduction studies, romiplostim may cause fetal harm if administered to a pregnant female.

Information related to the use of romiplostim in pregnancy is limited (Eslick 2019; Rosa María 2019).

Patient Education

What is this drug used for?

• It is used to raise platelet counts.
• It is used to treat immune thrombocytopenia (ITP).

Frequently reported side effects of this drug

• Dizziness
• Headache
• Joint pain
• Common cold symptoms
• Abdominal pain
• Throat pain or irritation
• Mouth pain or irritation
• Diarrhea
• Heartburn
• Painful extremities
• Nausea
• Vomiting
• Shoulder pain
• Muscle pain
• Muscle weakness
• Trouble sleeping

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Severe cerebrovascular disease like change in strength on one side is greater than the other, trouble speaking or thinking, change in balance, or vision changes
• Blood clots like numbness or weakness on one side of the body; pain, redness, tenderness, warmth, or swelling in the arms or legs; change in color of an arm or leg; chest pain; shortness of breath; fast heartbeat; or coughing up blood
• Burning or numbness feeling
• Bruising
• Bleeding
• Swelling of arms or legs
• Ear pain
• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.