Sargramostim (Monograph)

Brand name: Leukine
Drug class: Hematopoietic Agents

Medically reviewed by Drugs.com on Nov 20, 2023. Written by ASHP.

Introduction

Biosynthetic hematopoietic agent that affects the proliferation and differentiation of a variety of hematopoietic progenitor cells; recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF).

Uses for Sargramostim

Acute Myeloid Leukemia (AML) After Induction Chemotherapy

Used to accelerate neutrophil recovery and reduce the incidence of severe and life-threatening infections following induction chemotherapy in adults ≥55 years of age with AML.

Autologous Peripheral Blood Progenitor Cell (PBPC) Mobilization and Collection

Used to mobilize hematopoietic progenitor cells into peripheral blood for collection by leukapheresis in adults with cancer undergoing autologous hematopoietic stem cell transplantation (HSCT).

Autologous PBPC and Bone Marrow Transplantation (BMT)

Used to accelerate myeloid recovery following autologous PBPC or BMT in adults and pediatric patients ≥2 years of age with non-Hodgkin lymphoma (NHL), acute lymphoblastic leukemia (ALL), or Hodgkin lymphoma (HL).

Allogeneic BMT

Used to accelerate myeloid recovery in adults and pediatric patients ≥2 years of age undergoing allogeneic BMT from human leukocyte antigen (HLA)-matched related donors.

Allogeneic or Autologous BMT: Treatment of Delayed Neutrophil Recovery or Graft Failure

Used to increase survival in adults and pediatric patients ≥2 years of age who have undergone allogeneic or autologous BMT and in whom engraftment is delayed or has failed.

Acute Exposure to Myelosuppressive Doses of Radiation

Used to improve survival in adults and pediatric patients from birth to 17 years of age acutely exposed to myelosuppressive doses of radiation.

Sargramostim Dosage and Administration

General

Patient Monitoring

Monitor for signs and symptoms of infusion-related reactions such as respiratory distress, hypoxia, flushing, hypotension, syncope, and/or tachycardia.
Monitor body weight and hydration status during therapy.
Monitor CBC with differential twice weekly during therapy.

Administration

Administer by IV infusion or sub-Q injection; route of administration differs depending on indication for use.

Should be administered under the guidance and supervision of a clinician, but may be self-administered outside of a hospital or medical office setting (e.g., at home) if the clinician determines that the patient and/or caregiver is competent to prepare and safely administer the drug.

Do not administer concomitantly with or within 24 hours preceding cytotoxic chemotherapy or radiotherapy or within 24 hours following chemotherapy.

IV Administration

Do not administer IV infusion through an in-line membrane filter. Do not add other medications to infusion solutions containing sargramostim.

Generally infused IV over 2–4 hours. Also has been administered by IV infusion over 30–60 minutes, over 5–12 hours, or by continuous IV infusion over 24 hours.

Reconstitution

Reconstitute prior to administration by adding 1 mL of sterile water for injection (without preservative) or bacteriostatic water for injection (with 0.9% benzyl alcohol) to provide a single-dose solution containing 250 mcg/mL. Do not mix the contents of vials reconstituted with different diluents together. Reconstitute only with sterile water for injection (without preservative) when administering to neonates or infants in order to avoid benzyl alcohol exposure.

Dilution

Dilute the reconstituted solution in 0.9% sodium chloride injection. If the final concentration is <10 mcg/mL, add albumin (human) to a final concentration of 0.1% in order to prevent adsorption of sargramostim to the drug delivery system. Use immediately after dilution.

Sub-Q Administration

Reconstitution

Dilution

No further dilution of the reconstituted vial is required prior to sub-Q injection.

Dosage

Pediatric Patients

Autologous Peripheral Blood Progenitor Cell (PBPC) Transplantation in Pediatric Patients ≥2 Years of Age with NHL, ALL, or HL

IV

250 mcg/m²/day IV over 24 hours.

Initiate immediately after progenitor cell infusion and continue until ANC >1500 cells/mm³ for 3 consecutive days.

Sub-Q

250 mcg/m²/day once daily.

Initiate immediately after progenitor cell infusion and continue until ANC >1500 cells/mm³ for 3 consecutive days.

Autologous Bone Marrow Transplantation (BMT) in Pediatric Patients ≥2 Years of Age with NHL, ALL, or HL

IV

250 mcg/m²/day IV over 2 hours beginning 2 to 4 hours after bone marrow infusion, and not <24 hours after the last dose of chemotherapy or radiotherapy.

Do not administer until post marrow infusion ANC is <500 cells/mm³ and continue until ANC >1500 cells/mm³ for 3 consecutive days.

Allogeneic BMT in Pediatric Patients ≥2 Years of Age

IV

250 mcg/m²/day IV over 2 hours beginning 2 to 4 hours after bone marrow infusion, and not <24 hours after the last dose of chemotherapy or radiotherapy.

Do not administer until post marrow infusion ANC is <500 cells/mm³ and continue until ANC >1500 cells/mm³ for 3 consecutive days.

Obtain a CBC with differential twice weekly during therapy. If disease progression or blast cell appearance occurs, discontinue immediately. If grade 3 or 4 adverse reactions occur, reduce the dose by 50% or interrupt therapy until the reaction resolves. If WBC >50,000 cells/mm³ or ANC >20,000 cells/mm³occurs, interrupt therapy or reduce dose by 50%.

Allogeneic or Autologous BMT: Treatment of Delayed Neutrophil Recovery of Graft Failure in Pediatric Patients ≥2 years of age

IV

250 mcg/m²/day IV over 2 hours for 14 days.

If neutrophil recovery does not occur after 7 days off therapy, repeat the dose. If recovery still does not occur after another 7 days off therapy, administer a third course of sargramostim 500 mcg/m²/day for 14 days. If there is still no improvement, further dose escalation is unlikely to be beneficial.

Obtain a CBC with differential twice weekly during therapy. If disease progression or blast cell appearance occurs, discontinue immediately. If grade 3 or 4 adverse reactions occur, reduce dose by 50% or interrupt therapy until the reaction resolves. If WBC >50,000 cells/mm³ or ANC >20,000 cells/mm³ occurs, interrupt therapy or reduce dose by 50%.

Acute Exposure to Myelosuppressive Doses of Radiation in Pediatric Patients (Birth to 17 Years of Age)

Sub-Q

Weight-based dosing as follows:

For patients >40 kg: 7 mcg/kg once daily.

For patients 15 to 40 kg: 10 mcg/kg once daily.

For patients <15 kg: 12 mcg/kg once daily.

Initiate therapy as soon as possible after suspected or confirmed exposure to radiation doses >2 Gray.

Obtain a baseline CBC with differential and then serial CBCs approximately every third day. Continue therapy until ANC >1000 cells/mm³ for 3 consecutive CBCs or exceeds 10,000 cells/mm³ after a radiation-induced nadir. Do not delay therapy if a CBC is not readily available.

Estimate the level of radiation exposure via clinical findings, biodosimetry (if available), and information from public health authorities.

Adults

AML Following Induction Chemotherapy in Adults ≥55 Years of Age

IV

250 mcg/m²/day IV over 4 hours starting approximately on day 11 or four days following the completion of induction chemotherapy, if the day 10 bone marrow is hypoplastic with <5% blasts. If a second induction chemotherapy cycle is required, administer approximately 4 days after completion of chemotherapy if bone marrow is hypoplastic with <5% blasts. Continue therapy until ANC >1500 cells/mm³ for 3 consecutive days or a maximum of 42 days.

Obtain a CBC with differential twice weekly during therapy. If leukemic regrowth occurs, discontinue immediately. If grade 3 or 4 adverse reactions occur, reduce dose by 50% or interrupt therapy until the reaction resolves. If an ANC >20,000 cells/mm³ occurs, interrupt therapy or reduce the dose by 50%.

Autologous PBPC Mobilization and Collection

IV

250 mcg/m²/day IV over 24 hours.

Continue at the same dose throughout the PBPC collection period. Reduce dose by 50% if WBC >50,000 cells/mm³. If adequate PBPC collection is not achieved, consider other mobilization therapy.

Sub-Q

250 mcg/m²/day once daily.

Continue at the same dose throughout the PBPC collection period. Reduce dose by 50% if WBC >50,000 cells/mm³. If adequate PBPC collection is not achieved, consider other mobilization therapy.

Autologous PBPC Transplantation in Adults with NHL, ALL, or HL

IV

250 mcg/m²/day IV over 24 hours.

Initiate immediately after progenitor cell infusion and continue until ANC >1500 cells/mm³ for 3 consecutive days.

Sub-Q

250 mcg/m²/day once daily.

Initiate immediately after progenitor cell infusion and continue until ANC >1500 cells/mm³ for 3 consecutive days.

Autologous BMT in Adults with NHL, ALL or HL

IV

250 mcg/m²/day IV over 2 hours beginning 2 to 4 hours after bone marrow infusion, and not <24 hours after the last dose of chemotherapy or radiotherapy.

Do not administer until post marrow infusion ANC <500 cells/mm³ and continue until ANC >1500 cells/mm³ for 3 consecutive days.

Allogeneic BMT

IV

250 mcg/m²/day IV over 2 hours beginning 2 to 4 hours after bone marrow infusion, and not <24 hours after the last dose of chemotherapy or radiotherapy. Do not administer until post marrow infusion ANC <500 cells/mm³ and continue until ANC >1500 cells/mm³ for 3 consecutive days.

Obtain a CBC with differential twice weekly during therapy. If disease progression or blast cell appearance occurs, discontinue immediately. If grade 3 or 4 adverse reactions occur, reduce dose by 50% or interrupt therapy until the reaction resolves. If WBC >50,000 cells/mm³ or ANC >20,000 cells/mm³ occurs, interrupt therapy or reduce dose by 50%.

Allogeneic or Autologous BMT: Treatment of Delayed Neutrophil Recovery of Graft Failure

IV

250 mcg/m²/day IV over 2 hours for 14 days. If neutrophil recovery does not occur after 7 days off therapy, repeat the dose. If recovery still does not occur after another 7 days off therapy, administer a third course of sargramostim 500 mcg/m²/day for 14 days. If there is still no improvement, further dose escalation is unlikely to be beneficial.

Obtain a CBC with differential twice weekly during therapy. If disease progression or blast cell appearance occurs, discontinue immediately. If grade 3 or 4 adverse reactions occur, reduce dose by 50% or interrupt therapy until the reaction resolves. If WBC >50,000 cells/mm³ or ANC >20,000 cells/mm³ occurs, interrupt therapy or reduce the dose by 50%.

Acute Exposure to Myelosuppressive Doses of Radiation

Sub-Q

7 mcg/kg once daily. Initiate therapy as soon as possible after suspected or confirmed exposure to radiation doses >2 Gray.

Estimate the level of radiation exposure via clinical findings, biodosimetry (if available), and information from public health authorities.

Special Populations

Hepatic Impairment

No specific dosage recommendations.

Renal Impairment

No specific dosage recommendations.

Geriatric Use

No specific dosage recommendations.

Cautions for Sargramostim

Contraindications

History of serious allergic reactions, including anaphylaxis, to human GM-CSF, yeast-derived products, or any product component.

Warnings/Precautions

Hypersensitivity Reactions

Serious hypersensitivity reactions, including anaphylaxis, reported. Employ appropriate precautions in case a reaction occurs. Discontinue therapy if a serious allergic or anaphylactic reaction occurs and initiate medical management. Permanently discontinue therapy in patients who experience serious allergic reactions.

Infusion-related Reactions

Infusion-related reactions may occur following initial administration in a particular cycle. Observe patients closely for signs and symptoms of infusion-related reactions, especially those with pre-existing pulmonary disease. Reduce the rate of the sargramostim infusion by 50% if acute symptoms develop. Discontinue the infusion if symptoms persist or worsen despite dosage reduction. Administer subsequent IV infusions following the standard dose schedule with careful monitoring in those who experience infusion-related reactions.

Risk of Severe Myelosuppression

Do not administer sargramostim with or within 24 hours prior to cytotoxic chemotherapy or radiotherapy or within 24 hours following chemotherapy due to an increased risk of severe myelosuppression.

Effusions and Capillary Leak Syndrome

Edema, capillary leak syndrome, and pleural and/or pericardial effusion reported. Administration of sargramostim may aggravate preexisting fluid retention. Dose reduction or interruption of sargramostin, with or without diuretic therapy, may reverse therapy-related fluid retention. Use sargramostim with caution in patients with preexisting fluid retention, pulmonary infiltrates, or heart failure. Monitor body weight and hydration status during sargramostim administration.

Supraventricular Arrhythmias

Supraventricular arrhythmias reported, particularly in patients with a history of cardiac arrhythmia. Discontinuation of sargramostim may reverse arrhythmic effects. Use sargramostim with caution in patients with preexisting cardiac disease.

Leukocytosis

Leukocytosis (WBC ≥50,000 cells/mm³) reported. Monitor CBC with differential twice weekly and consider whether to reduce the dose of sargramostim, or interrupt treatment, based on the clinical condition of the patient. Following discontinuation, a return to normal or baseline blood count levels generally occurs within 3 to 7 days.

Potential Effect on Malignant Cells

May potentially act as a growth factor for any tumor type, especially myeloid malignancies. Exercise caution when administering sargramostim to patients with a malignancy with myeloid characteristics. Discontinue treatment if progression occurs during therapy.

Immunogenicity

Anti-drug neutralizing antibodies were reported in 82.9% of patients receiving sargramostim for up to 12 months in a clinical study for an unapproved use. Administer sargramostim for the shortest necessary duration.

Risk of Serious Reactions in Infants Due to Benzyl Alcohol

Administration of solutions containing benzyl alcohol to neonates and low birth weight infants may result in serious and fatal adverse reactions including “gasping syndrome”. Avoid administration of sargramostim for injection reconstituted with Bacteriostatic Water for Injection (0.9% benzyl alcohol) in these patients. Administer these patients lyophilized sargramostim reconstituted with Sterile Water for Injection instead. Consider the combined daily metabolic load of benzyl alcohol from all sources if benzyl alcohol-reconstituted sargramostim must be used in neonates and low birth weight infants.

Specific Populations

Pregnancy

Limited data on use in pregnant women; may cause embryofetal harm based on animal findings. Advise women of childbearing potential of potential fetal risks.

Benzyl alcohol, a preservative present in Bacteriostatic Water for Injection, has been associated with gasping syndrome in neonates and low birth weight infants. If sargramostim is necessary during pregnancy, reconstitute the drug only with Sterile Water for Injection without preservatives.

Lactation

It is not known whether sargramostim is distributed into milk, affects milk production, or affects the breast-fed infant. Advise lactating women not to breast-feed during treatment and for at least 2 weeks after the last dose of sargramostim.

Pediatric Use

The efficacy and safety of sargramostim have been established in pediatric patients ≥2 years of age for autologous peripheral blood progenitor cells and BMT, allogeneic BMT, and treatment of delayed neutrophil recovery or graft failure based on studies performed in adults and a limited number of pediatric patients. The efficacy and safety of sargramostim have also been established in the setting of acute exposure to myelosuppressive doses of radiation among pediatric patients from birth to 17 years of age.

In neonates and low birth weight infants, avoid the use of sargramostim solutions reconstituted with Bacteriostatic Water for Injection due to the presence of the preservative, benzyl alcohol.

Geriatric Use

Experience in patients ≥65 years of age is insufficient to determine whether they respond differently to sargramostim than younger patients.

Common Adverse Effects

Most common (>30%) adverse reactions in recipients of autologous BMT include: fever, nausea, diarrhea, vomiting, mucus membrane disorder, alopecia, asthenia, malaise, anorexia, rash, GI disorder, edema.

Most common (>30%) adverse reactions in recipients of allogeneic BMT include: diarrhea, fever, nausea, rash, vomiting, stomatitis, anorexia, increased glucose, alopecia, abdominal pain, low albumin, headache, hypertension.

Most common (>30%) adverse reactions in patients with AML include: fever, liver toxicity, skin reactions, infections, metabolic laboratory abnormalities, nausea, diarrhea, genitourinary abnormalities, pulmonary toxicity, vomiting, neurotoxicity, stomatitis, alopecia, weight loss.

Drug Interactions

Drugs with Myeloproliferative Effects

Avoid drugs that could potentiate the myeloproliferative effects of sargramostim (e.g., lithium, corticosteroids). If concomitant use is unavoidable, monitor patients frequently for clinical and laboratory signs of increased myeloproliferative effects.

Sargramostim Pharmacokinetics

Absorption

Bioavailability

Peak serum concentrations are attained during or immediately after completion of an IV infusion.

Sargramostim was detected within 15 minutes and reached peak serum concentrations between 2.5 and 4 hours after sub-Q administration.

When compared to the IV route, the absolute bioavailability with the sub-Q route was 75%.

Elimination

Metabolism

Not known whether sargramostim is metabolized or how it is eliminated from the body.

Since sargramostim is a protein, expected to degrade to small peptides and individual amino acids.

Half-life

1.4 hours following sub-Q administration.

Stability

Storage

Parenteral

Store single-dose vials under refrigeration (2-8°C) in their original carton; do not freeze or shake and protect from light.

Store reconstituted solution under refrigeration (2-8°C); do not freeze.

Actions

Affects the proliferation and differentiation of a variety of hematopoietic progenitor cells.
Prepared using recombinant DNA technology and a yeast expression system that utilizes Saccharomyces cerevisiae.
Has an amino acid sequence identical to that of endogenous human GM-CSF except for a leucine instead of a proline at position 23 and potentially a different carbohydrate moiety.
Appears to elicit the pharmacologic effects usually produced by endogenous human GM-CSF.

Advice to Patients

Instruct patients who self-administer sargramostim as to the proper dose, reconstitution and administration procedures, and disposal of needles and syringes.
Advise patients of the potential risk of serious allergic and infusion-related reactions.
Inform patients of the potential risk for fluid retention. Patients should monitor body weight and hydration status during therapy.
Advise patients with preexisting cardiac disease of the potential development of arrhythmias with therapy.
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.
Importance of informing patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.