Romiplostim

• Chronic Immune Thrombocytopenia
• ITP After Splenectomy Failure
• Thrombocytopenia

Romiplostim is a thrombopoietin receptor agonist (TPO-RA) used to treat chronic immune thrombocytopenia (ITP) in patients who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy. It stimulates platelet production through the same receptor as endogenous thrombopoietin.

Mechanism of Action

Romiplostim mimics endogenous thrombopoietin (TPO):

• TPO receptor (c-Mpl) agonist: Binds and activates the TPO receptor on megakaryocytes
• Stimulates megakaryocyte proliferation: Increases bone marrow megakaryocyte numbers
• Enhances platelet production: Promotes megakaryocyte maturation and platelet release
• Different binding site from TPO: Does not compete with or induce antibodies against endogenous TPO

Romiplostim is a peptibody (peptide fused to an Fc carrier domain) with no sequence homology to endogenous TPO.

Available Formulations

Romiplostim is available as lyophilized powder for subcutaneous injection:

• 125 mcg, 250 mcg, 500 mcg single-dose vials

Reconstitute with preservative-free sterile water for injection.

Medical Uses

FDA-Approved Indications:

• Chronic immune thrombocytopenia (ITP) in adults who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy
• Chronic ITP in pediatric patients 1 year and older who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy

Dosing Guidelines

Adults:

• Initial: 1 mcg/kg subcutaneously once weekly
• Adjust by increments of 1 mcg/kg weekly to maintain platelet count ≥50,000/mcL
• Maximum: 10 mcg/kg weekly
• Discontinue if platelet count does not increase after 4 weeks at maximum dose

Pediatric (≥1 year):

• Initial: 1 mcg/kg subcutaneously once weekly
• Adjust to maintain platelet count ≥50,000/mcL

Dose Adjustments:

• Increase by 1 mcg/kg if platelets <50,000/mcL after 2 weeks
• Reduce by 1 mcg/kg if platelets >200,000/mcL for 2 consecutive weeks
• Hold dose if platelets >400,000/mcL

Important Safety Information

Warnings and Precautions:

• Thrombotic/thromboembolic complications: May occur at elevated platelet counts; do not normalize platelet counts
• Bone marrow reticulin formation: Monitor CBC and peripheral smear for abnormalities; discontinue if fibrosis suspected
• Progression of myelodysplastic syndromes (MDS): Not for MDS; exclude MDS before initiating
• Worsening thrombocytopenia after discontinuation: Platelet counts may drop below baseline; monitor for bleeding
• Loss of response: May develop neutralizing antibodies

REMS Program: Not currently required but prescribers should be experienced in treating ITP.

Drug Interactions

No formal drug interaction studies have been conducted. As a protein therapeutic, romiplostim is not expected to interact with cytochrome P450 enzymes.

Considerations:

• Anticoagulants/antiplatelets: Use with caution if platelet counts become elevated
• Other ITP medications: May need to reduce other ITP treatments as platelet counts increase

Special Populations

• Hepatic Impairment: Not formally studied
• Renal Impairment: Not formally studied
• Pregnancy: Limited data; may cross placenta
• Lactation: Unknown if excreted in milk
• Elderly: No specific adjustment; use with caution
• Pediatric: Approved for ≥1 year with chronic ITP