Usage
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Romiplostim is primarily prescribed for the treatment of chronic Immune Thrombocytopenia (ITP), a condition characterized by low platelet counts (thrombocytopenia) that increases bleeding risk. It is specifically indicated for adult patients who have not responded adequately to other treatments like corticosteroids, immunoglobulins, or splenectomy. It has also shown efficacy in treating children 1 year and older with chronic ITP. Additionally, romiplostim is approved for use in emergency situations involving acute radiation syndrome (ARS) where myelosuppressive doses of radiation have been absorbed.
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Pharmacological Classification: Thrombopoietin Receptor Agonist.
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Mechanism of Action: Romiplostim mimics the action of thrombopoietin, a naturally occurring hormone that stimulates the production of platelets in the bone marrow. By binding to and activating the thrombopoietin receptor, romiplostim increases platelet production, reducing bleeding risk in ITP.
Alternate Names
How It Works
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Pharmacodynamics: Romiplostim binds to the thrombopoietin receptor (c-Mpl) on megakaryocytes, the precursor cells to platelets, and stimulates their proliferation and differentiation. This leads to an increased production of platelets. The effect on the body is a raise in platelet count, thus mitigating bleeding risk. Note: Achieving normal platelet levels isn’t the typical therapeutic goal.
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Pharmacokinetics:
- Absorption: Administered subcutaneously, romiplostim exhibits dose-proportional absorption.
- Metabolism: The specific metabolic pathways are not fully characterized, but it is thought that romiplostim is cleared primarily through the same mechanisms as endogenous thrombopoietin, potentially involving target-mediated elimination via binding to the thrombopoietin receptor on platelets.
- Elimination: Romiplostim’s elimination is multiphasic, with a terminal half-life typically ranging from 1 to 7 days.
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Mode of Action: Romiplostim acts as a thrombopoietin receptor agonist, binding to and activating the c-Mpl receptor on the surface of megakaryocytes. This activation triggers intracellular signaling pathways that promote megakaryocyte growth and maturation, ultimately leading to an increased production of platelets.
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Receptor Binding: Binds to the transmembrane domain of the thrombopoietin receptor (c-Mpl).
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Elimination Pathways: Target-mediated elimination via binding to c-Mpl on platelets and subsequent degradation.
Dosage
Standard Dosage
Adults:
- Initial Dose: 1 mcg/kg subcutaneously once weekly.
- Dose Adjustments: Adjust the weekly dose by increments of 1 mcg/kg until a platelet count of at least 50 x 109/L is reached. The maximum weekly dose is 10 mcg/kg. Periodic monitoring and adjustments are required to maintain optimal platelet counts.
Children (1 year and older):
- Initial Dose: 1 mcg/kg subcutaneously once weekly.
- Dose Adjustments: Similar to adults, adjust the weekly dose by increments of 1 mcg/kg until a platelet count of at least 50 x 109/L is reached, not exceeding a maximum weekly dose of 10 mcg/kg. Monitor platelet counts weekly until stable, then monthly.
Special Cases:
- Elderly Patients: No specific dosage adjustments are recommended, though patients should be carefully monitored due to the potential increased bleeding risk associated with age and other potential co-morbidities.
- Patients with Renal Impairment: No specific dosage adjustments are routinely required, but use with caution and monitor closely.
- Patients with Hepatic Dysfunction: Use with caution, especially in moderate to severe hepatic impairment (Child-Pugh score ≥ 7), due to increased risk of portal vein thrombosis. Closely monitor platelet counts.
- Patients with Comorbid Conditions: Careful consideration and closer monitoring are warranted, especially for patients with a history of blood clots or thromboembolic events.
Clinical Use Cases
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Acute Radiation Syndrome (ARS) Due to Myelosuppressive Radiation Exposure: 10 mcg/kg as a single subcutaneous injection administered as soon as possible after exposure.
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Intubation, Surgical Procedures, Mechanical Ventilation, ICU Use, Emergency Situations (other than radiation exposure): Romiplostim is not indicated for these situations. Dosage adjustments in these cases are applicable to pre-existing ITP treatment with romiplostim and will be guided by the patient’s platelet counts and clinical condition. Consult hematology if guidance is required.
Dosage Adjustments:
- Dosage adjustments are based on the platelet count response. Increase the dose incrementally if the desired platelet level isn’t achieved. Reduce the dose if the platelet count exceeds the therapeutic range. Always adhere to the maximum weekly dose limit. Consider patient-specific factors, including comorbidities like hepatic or renal dysfunction, when adjusting doses.
Side Effects
Common Side Effects:
- Headache
- Joint/Muscle pain
- Dizziness
- Tingling/numbness in hands/feet
- Fatigue
- Upper respiratory tract infection
- Nausea
- Diarrhea
- Abdominal pain
Rare but Serious Side Effects:
- Blood clots (thrombosis/thromboembolism): Stroke, heart attack, pulmonary embolism, deep vein thrombosis.
- Worsening of precancerous blood conditions like myelodysplastic syndromes (MDS) to acute myeloid leukemia (AML)
- Rebound thrombocytopenia upon discontinuation of treatment, significantly increasing bleeding risk
- Allergic reactions, including anaphylaxis
Long-Term Effects:
- Bone marrow reticulin formation (increased fibrous tissue in bone marrow)
Contraindications
- Absolute: Hypersensitivity to romiplostim, E. coli-derived proteins, any component of the formulation, or history of severe allergic reactions.
- Myelodysplastic syndromes (MDS) excluding patients with chronic ITP.
Drug Interactions
- Romiplostim can be used with other ITP treatments, including corticosteroids, danazol, azathioprine, intravenous immunoglobulin (IVIG), and anti-D immunoglobulin. Monitor platelet counts closely during combination therapy.
- The potential for interactions with drugs highly bound to plasma proteins is unknown.
- Consult drug interaction checkers for a complete list of potential interactions.
Pregnancy and Breastfeeding
- Pregnancy: Limited data available. Animal studies suggest potential fetal harm. Use only if the benefit clearly outweighs the risk. A pregnancy surveillance program is available. Contact 1-800-772-6436 (US).
- Breastfeeding: Romiplostim may pass into breast milk. Discontinue breastfeeding or the drug, considering the risks and benefits to both mother and infant.
Drug Profile Summary
- Mechanism of Action: Thrombopoietin receptor agonist stimulating platelet production.
- Side Effects: Headache, joint/muscle pain, dizziness, fatigue, blood clots, rebound thrombocytopenia.
- Contraindications: Hypersensitivity, MDS (excluding chronic ITP patients)
- Drug Interactions: Consult a drug interaction checker. Can be used with other ITP treatments but monitor carefully.
- Pregnancy & Breastfeeding: Potentially harmful; use with caution. Consider pregnancy registry and breastfeeding surveillance program.
- Dosage: Adults/Children: 1 mcg/kg SC weekly, titrated to platelet response, max 10 mcg/kg/week. ARS (radiation exposure): 10 mcg/kg SC single dose.
- Monitoring Parameters: Platelet counts (weekly until stable, then monthly), complete blood counts (CBCs), liver function tests (LFTs), renal function tests, bone marrow assessments if indicated.
Popular Combinations
Precautions
- General Precautions: Monitor blood counts regularly. Evaluate for pre-existing liver disease, renal impairment, bleeding disorders, and history of blood clots.
- Specific Populations:
- Pregnant Women: Potential fetal risks; use only if absolutely necessary.
- Breastfeeding Mothers: Potential for neonatal exposure.
- Children & Elderly: Monitor carefully, especially the elderly due to increased comorbidities.
- Lifestyle Considerations: Alcohol, smoking, or other factors impacting bleeding risk should be addressed with patients.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Romiplostim?
A: The initial dose is 1 mcg/kg subcutaneously once weekly for both adults and children (1 year and older). Adjust the weekly dose by increments of 1 mcg/kg until a platelet count of at least 50 x 109/L is reached, without exceeding 10 mcg/kg per week.
Q2: How is Romiplostim administered?
A: Subcutaneous injection once weekly.
Q3: What is the primary use of Romiplostim?
A: Treatment of chronic Immune Thrombocytopenia (ITP) in adults and children who have not responded to other treatments. Also used in emergency management of acute radiation syndrome due to myelosuppressive radiation exposure.
Q4: What are the common side effects of Romiplostim?
A: Headache, joint and muscle pain, dizziness, fatigue, upper respiratory tract infection, and gastrointestinal disturbances like nausea and diarrhea.
Q5: What are the serious side effects of Romiplostim?
A: Blood clots, worsening of MDS to AML (in patients without ITP), rebound thrombocytopenia, and allergic reactions (including anaphylaxis).
Q6: Can Romiplostim be used during pregnancy?
A: Limited data are available. Only use if the potential benefit justifies the risk to the fetus. Enroll in the pregnancy surveillance program.
Q7: Can Romiplostim be used during breastfeeding?
A: It may pass into breast milk. Discontinue breastfeeding or the drug, weighing the risks and benefits for mother and baby.
Q8: What are the contraindications for Romiplostim?
A: Hypersensitivity to the drug or its components and MDS excluding patients with chronic ITP.
Q9: Are there any specific monitoring requirements during Romiplostim therapy?
A: Yes. Platelet counts should be monitored weekly until stable, then monthly. Complete blood counts, liver and kidney function tests should also be monitored regularly. Bone marrow examination may be necessary if there are concerns about reticulin formation.
Q10: What should be done if a patient experiences rebound thrombocytopenia after stopping Romiplostim?
A: Closely monitor platelet counts weekly for at least two weeks after discontinuation. If thrombocytopenia is severe or bleeding occurs, consider restarting Romiplostim or other appropriate ITP treatments as directed by a hematologist.
