sargramostim

Action and Spectrum

Mechanism of action 

The primary mechanism of action of sargramostim is to stimulate the production and maturation of white blood cells, particularly granulocytes and macrophages. These cells play a vital role in the body’s immune system by fighting off infections and foreign substances. It also promotes the recovery of white blood cells after chemotherapy or radiation therapy 

Spectrum 

It has a broad spectrum of activity, including the promotion of white blood cell recovery after chemotherapy or radiation therapy, the treatment of neutropenia (low levels of white blood cells), the treatment of certain types of cancer, and reducing the incidence of serious infections in patients with HIV/AIDS. It has been used in the treatment of various types of cancer such as leukaemia, non-Hodgkin’s lymphoma, and breast cancer 

Drug Interaction

Adverse Reaction

Frequency defined:  

>10% 

Autologous bone marrow transplantation 

Diarrhea 

Malaise 

Chest pain 

Abdominal pain 

Asthenia 

Rash 

Peripheral edema 

Acute myelogenous leukemia 

Skin reactions 

Nausea 

Weight loss 

Nausea 

Abdominal pain 

Rigor 

Pericardial effusion 

Bone pain 

Hypercholesterolemia 

Chest pain 

Fever 

Metabolic disease 

Vomiting 

Pruritis 

Pharyngitis 

Myalgia 

Arthralgia 

Intraocular hemorrhage 

Hematemesis 

1-10% 

Pericardial effusion 

Cardiac dysrhythmia 

<1% 

Capillary leak syndrome 

Frequency undefined:  

Fever 

Cerebral hemorrhage 

Sepsis 

Anorexia 

Malaise 

Stomatitis 

Renal failure 

Black Box Warning

Contraindication / Caution

Contraindications 

It should not be administered to patients with a history of severe allergic reactions (e.g., anaphylaxis) to human GCSFs (such as sargramostim), yeast-derived products, or any product component. It should not be administered to patients with greater than 10% leukemic myeloid blasts in their bone marrow or peripheral blood. It should not be administered within 24 hours preceding or following chemotherapy or radiotherapy. 

Caution 

caution in fluid retention, pulmonary infiltrates, CHF, lung disease, cardiac disease, hypoxia, hepatic/renal impairment; conditions may worsen. 

Pregnancy / Lactation

Pregnancy consideration: Insufficient data available 

Lactation: Excretion of the drug in human breast milk is unknown 

Pregnancy category: 

Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester.   

Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    

Category D: adequate data available with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.    

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    

Category N: There is no data available for the drug under this category 

Pharmacology

Pharmacology 

It is also a recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF) and is a synthetic form of the naturally occurring GM-CSF protein. It acts on hematopoietic cells by binding to specific receptors on their surface, stimulating their proliferation and differentiation, particularly into neutrophils, monocytes/macrophages, and myeloid-derived dendritic cells. Additionally, it also has some end-cell function activity. This increases the number of white blood cells in the body, which can help boost the immune system and fight off infections. It is used to treat neutropenia and certain types of cancer and reduce the incidence of severe infections in patients with HIV/AIDS 

Pharmacodynamics 

The effects of sargramostim include an increase in circulating neutrophils and other white blood cells, which can help boost the immune system and fight off infections. It also has some end-cell function activity, which can enhance the activity of white blood cells and increase the production of other cytokines. 

The pharmacodynamic effects are dose-dependent, with higher doses resulting in a more significant increase in white blood cells.  

Pharmacokinetics 

Absorption:  

The peak plasma concentration of sargramostim is 16.7 ng/mL when administered intravenously and 3.03 ng/mL subcutaneously. The area under the curve (AUC) is 32.9 ng·hr/mL when administered intravenously and 21.3 ng·hr/mL when administered subcutaneously. The bioavailability of sargramostim is 75% when administered subcutaneously.  

Distribution:  

When administered intravenously, the volume of distribution (Vd) of sargramostim is 96.8 L. 

Metabolism:  

Proteolytic degradation is metabolized in the body, breaking down proteins into smaller peptides and amino acids. The metabolic breakdown of sargramostim occurs primarily in the liver and the kidneys. 

Elimination/Excretion:  

The half-life elimination of sargramostim is 3.84 h when administered intravenously and 1.4 h when administered subcutaneously. The clearance of sargramostim is 17.2L/h 

Adminstartion

Administration 

Subcutaneous administration 

The injection should not be administered simultaneously with or within 24 hours preceding cytotoxic chemotherapy or radiotherapy or within 24 hours following chemotherapy. 

Also, sargramostim injection is formulated as a sterile solution preserved with 1.1% benzyl alcohol and should appear as a clear, colorless single-dose solution. 

It is important to use only sargramostim for injection (lyophilized powder) reconstituted with sterile water for injection without preservatives when administering to neonates or infants to avoid benzyl alcohol exposure as it can cause toxicity in neonates and infants. 

Intravenous administration 

When administering sargramostim, it is essential not to use an inline membrane filter for IV infusions. Other medications should only be added to infusion solutions containing Sargramostim with compatibility and stability information. 

Using only 0.9%, NaCl is recommended to prepare IV infusion solutions. It’s important to visually inspect the solution for particulate matter and discoloration before administration. The vial should not be used if particulate matter is present or the solution is discolored. 

sargramostim is usually infused over 2-4 hours, although longer, shorter, or continuous infusions have been done. It’s essential to follow the instructions provided by the healthcare provider or the package insert for the appropriate administration method and duration. 

Storage 

Unused vials of sargramostim should be refrigerated at 2-8°C (36-46°F) in the original carton to protect them from light. They should not be frozen or shaken, or used beyond the expiration date printed on the vial. 

Diluted solutions or reconstituted vials of sargramostim should also be refrigerated at 2-8°C (36-46°F) for up to 20 days once the vial has been entered. It’s essential to discard any remaining solution after 20 days and not to freeze the solution 

Patient Information Leaflet

Patient information leaflet 

Generic Name: sargramostim 

Pronounced:  [ sar-GRA-moe-stim ] 

Why do we use sargramostim? 

A modified version of human granulocyte-macrophage colony-stimulating factor called sargramostim is used to boost the generation of immune cells after myelosuppressive therapy or bone marrow transplant.