Usage
Sargramostim is prescribed to stimulate the production of white blood cells (leukocytes), particularly neutrophils, in patients with neutropenia (low neutrophil count). It is also used to accelerate myeloid recovery after bone marrow transplantation and to mobilize peripheral blood progenitor cells (PBPCs) for collection. It is categorized as a colony-stimulating factor (CSF). Sargramostim’s mechanism of action involves binding to specific cell surface receptors (granulocyte-macrophage colony-stimulating factor receptors) on hematopoietic progenitor cells in the bone marrow, promoting their proliferation and differentiation into various types of blood cells, including neutrophils.
Alternate Names
Sargramostim is also known as granulocyte-macrophage colony-stimulating factor (GM-CSF). A popular brand name for Sargramostim is Leukine.
How It Works
Pharmacodynamics: Sargramostim primarily stimulates the bone marrow to produce neutrophils, eosinophils, monocytes, and macrophages, thereby increasing white blood cell counts and enhancing immune function.
Pharmacokinetics:
- Absorption: Sargramostim can be administered intravenously (IV) or subcutaneously (SC). Subcutaneous administration has a bioavailability of approximately 50%.
- Metabolism and Elimination: The metabolism and elimination pathways of sargramostim are not fully characterized. It is likely metabolized in various tissues, and the elimination half-life after intravenous administration is around 2 hours.
- Mode of Action: Sargramostim binds to the GM-CSF receptor, a heterodimer consisting of an alpha and a beta subunit, located on the surface of hematopoietic progenitor cells. This binding activates intracellular signaling pathways that promote cell growth, differentiation, and survival, leading to increased production of myeloid cells.
Dosage
Standard Dosage
Adults:
- Neutropenia: 250 mcg/m² IV over 2 hours or SC once daily.
- Bone Marrow Transplantation: 250 mcg/m² IV over 2 hours starting 2-4 hours post-transplant.
- PBPC Mobilization: 250 mcg/m² IV over 24 hours or SC once daily.
- Acute Radiation Syndrome: 7 mcg/kg SC once daily.
Children:
- Acute Radiation Syndrome: <15 kg: 12 mcg/kg SC once daily; 15-40 kg: 10 mcg/kg SC once daily; >40 kg: 7 mcg/kg SC once daily.
- Other Indications: Safety and efficacy in children younger than 2 years old haven’t been firmly established. Dosing above 2 years of age is generally weight-based and condition-specific.
Special Cases:
- Elderly Patients: No specific dose adjustments are typically required, but careful monitoring is recommended.
- Patients with Renal Impairment: No specific dose adjustments are usually necessary, but close monitoring of renal function is advised.
- Patients with Hepatic Dysfunction: No specific dose adjustments are typically needed, but monitor liver function closely.
- Patients with Comorbid Conditions: Dosage adjustments may be required for patients with fluid retention, pre-existing cardiac or pulmonary conditions.
Clinical Use Cases:
Dosing generally follows standard guidelines and is tailored based on the clinical indication and patient-specific factors. Specific use cases in intensive care, during surgical procedures, or intubation should be guided by hematologic parameters and clinical response. Sargramostim is not typically indicated for emergency situations like cardiac arrest or status epilepticus.
Dosage Adjustments:
Dose reductions or discontinuation may be necessary if white blood cell counts increase excessively or if severe side effects occur. Adjustments may be necessary based on patient tolerance and clinical response.
Side Effects
Common Side Effects:
Bone pain, fever, injection site reactions, weakness, headache, nausea, vomiting, diarrhea, rash, muscle pain, chills.
Rare but Serious Side Effects:
Allergic reactions (including anaphylaxis), fluid retention, breathing difficulties, heart rhythm abnormalities, liver dysfunction.
Long-Term Effects: Data on long-term side effects are limited.
Adverse Drug Reactions (ADR):
Serious allergic reactions, severe fluid retention, pericardial effusion, capillary leak syndrome.
Contraindications
Hypersensitivity to sargramostim or any components of the formulation, excessive myeloid blasts in bone marrow or blood, concurrent administration with chemotherapy or radiotherapy (within 24 hours).
Drug Interactions
Sargramostim may interact with corticosteroids, lithium, and other drugs that stimulate myeloid cell production. Concurrent use of chemotherapy or radiotherapy should be avoided. It is important to review the patient’s medication list for potential interactions.
Pregnancy and Breastfeeding
Sargramostim is classified as Pregnancy Category C. There are no adequate and well-controlled studies in pregnant women. It should be used during pregnancy only if clearly needed. It is not known whether sargramostim is excreted in human milk. Because of the potential for adverse effects in nursing infants, breastfeeding is not recommended during treatment and for 2 weeks after the last dose.
Drug Profile Summary
- Mechanism of Action: Stimulates proliferation and differentiation of myeloid progenitor cells.
- Side Effects: Bone pain, fever, injection site reactions, fluid retention, allergic reactions.
- Contraindications: Hypersensitivity, excessive myeloid blasts, concurrent chemotherapy/radiotherapy.
- Drug Interactions: Corticosteroids, lithium.
- Pregnancy & Breastfeeding: Category C; breastfeeding not recommended.
- Dosage: Varies depending on indication; typically 250 mcg/m² IV or SC.
- Monitoring Parameters: Complete blood counts (CBCs), especially neutrophil counts, and monitoring for signs and symptoms of fluid overload.
Popular Combinations
Sargramostim is sometimes used in combination with other chemotherapy agents or growth factors, depending on the clinical context.
Precautions
Monitor closely for fluid retention, respiratory symptoms, and cardiac abnormalities. Evaluate hepatic and renal function. Patients should report any new or worsening shortness of breath, edema, or unusual weight gain.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Sargramostim?
A: The dosage varies based on the indication and patient-specific factors. Standard adult doses range from 250 mcg/m² for neutropenia and bone marrow transplantation to 7 mcg/kg for acute radiation syndrome. Pediatric dosing is weight-based.
Q2: How is Sargramostim administered?
A: Sargramostim can be administered intravenously (IV) over 2-24 hours or subcutaneously (SC).
Q3: What are the common side effects of Sargramostim?
A: Common side effects include bone pain, fever, injection site reactions, weakness, headache, nausea, vomiting, and diarrhea.
Q4: What are the serious side effects of Sargramostim?
A: Serious side effects include allergic reactions, fluid retention, breathing difficulties, and abnormal heart rhythms.
Q5: What are the contraindications for Sargramostim?
A: Contraindications include hypersensitivity to sargramostim, excessive myeloid blasts, and concurrent use with chemotherapy or radiotherapy.
Q6: Can Sargramostim be used during pregnancy?
A: Sargramostim is a Pregnancy Category C drug and should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Q7: Can Sargramostim be used during breastfeeding?
A: Breastfeeding is not recommended during Sargramostim treatment and for two weeks after the last dose due to the potential for adverse effects in the infant.
Q8: How should I monitor patients receiving Sargramostim?
A: Closely monitor complete blood counts (CBCs), particularly neutrophil counts. Watch for signs and symptoms of fluid overload, respiratory distress, and cardiac complications.
Q9: What are the drug interactions of Sargramostim?
A: Sargramostim may interact with corticosteroids, lithium, and other drugs that stimulate myeloid cell production. Be cautious of concomitant use with myelosuppressive agents.
Q10: What is the mechanism of action of Sargramostim?
A: Sargramostim binds to the GM-CSF receptor on hematopoietic progenitor cells, stimulating their proliferation and differentiation into neutrophils and other myeloid cells.
