Version May 2024
Dosage guidance:
Dosing: May round the dose to the nearest vial size (ASCO [Ozer 2000]).
Acute myeloid leukemia, following induction chemotherapy: Adults ≥55 years: IV: 250 mcg/m2/day (infused over 4 hours) starting approximately on day 11 or 4 days following the completion of induction chemotherapy (if day 10 bone marrow is hypoplastic with <5% blasts), continue until ANC >1,500/mm3 for 3 consecutive days or a maximum of 42 days. Do not administer within 24 hours before or after chemotherapy or radiation therapy.
If a second cycle of chemotherapy is necessary, administer ~4 days after the completion of chemotherapy if the bone marrow is hypoplastic with <5% blasts.
Allogeneic bone marrow transplantation, myeloid reconstitution: IV: 250 mcg/m2/day (infused over 2 hours), begin 2 to 4 hours after the bone marrow infusion and at least 24 hours after chemotherapy or radiotherapy, do not initiate until the post marrow infusion ANC is <500/mm3, and continue until ANC >1,500/mm3 for 3 consecutive days.
Allogeneic or autologous bone marrow transplantation, treatment of delayed neutrophil recovery or graft failure: IV: 250 mcg/m2/day (infused over 2 hours) for 14 days; If engraftment has not occurred after 7 days off sargramostim, may repeat. If neutrophil recovery still has not occurred after 7 days off sargramostim, a third course of 500 mcg/m2/day for 14 days may be attempted. If there is still no improvement, it is unlikely that further dose escalation will be of benefit.
Autologous peripheral blood progenitor cell mobilization and collection: IV, SUBQ: 250 mcg/m2/day IV (infused over 24 hours) or SUBQ once daily; continue the same dose throughout peripheral blood progenitor cell collection period.
Note: The optimal schedule for peripheral blood progenitor cell collection has not been established (usually begun 5 days after sargramostim and performed daily until protocol specified targets are achieved). If adequate numbers of progenitor cells are not collected, consider other mobilization therapy.
Autologous peripheral blood progenitor cell transplantation, myeloid reconstitution: IV, SUBQ: 250 mcg/m2/day IV (infused over 24 hours) or SUBQ once daily beginning immediately following infusion of progenitor cells; continue until ANC is >1,500/mm3 for 3 consecutive days. Do not administer within 24 hours before or after chemotherapy or radiation therapy.
Autologous bone marrow transplantation, myeloid reconstitution: IV: 250 mcg/m2/day (infused over 2 hours), begin 2 to 4 hours after the bone marrow infusion and at least 24 hours after chemotherapy or radiotherapy, do not initiate until the post marrow infusion ANC is <500/mm3, and continue until ANC >1,500/mm3 for 3 consecutive days. Do not administer within 24 hours before or after chemotherapy or radiation therapy.
Hematopoietic radiation injury syndrome, acute: SUBQ: Adults >40 kg: 7 mcg/kg once daily; begin as soon as possible after suspected or confirmed exposure to radiation doses >2 (gray) Gy; do not delay sargramostim if CBC is not readily available; continue sargramostim until ANC remains >1,000/mm3 for 3 consecutive CBCs (obtain CBCs approximately every 3 days) or ANC exceeds 10,000/mm3 after radiation-induced nadir.
Off-label dosing: SUBQ: 250 mcg/m2/day; continue until ANC >1,000/mm3 (Waselenko 2004). ASCO guidelines recommend initiating within 24 hours of exposure of a dose ≥2 Gy and/or significant decrease in absolute lymphocyte count, or for anticipated neutropenia <500/mm3 for ≥7 days (ASCO [Smith 2015]).
Neuroblastoma, high risk, relapsed or refractory (off-label use): SUBQ: 250 mcg/m2/day for 5 days on days −4 to 0, followed by 500 mcg/m2/day for 5 days on days 1 to 5 of each 4-week treatment cycle (in combination with naxitamab; on naxitamab days, administer sargramostim at least 1 hour prior to naxitamab) (Danyelza product labeling; Kushner 2019). Note: Treatment cycles are repeated every 4 weeks until complete or partial response, followed by 5 additional cycles (every 4 weeks). Subsequent cycles may be repeated every 8 weeks. Discontinue (naxitamab and GM-CSF) with disease progression or unacceptable toxicity. Refer to Naxitamab monograph for naxitamab dosing and premedication/pain management recommendations.
Primary prophylaxis of neutropenia in patients receiving chemotherapy (outside transplant and AML) or who are at high risk for neutropenic fever (off-label use):
Note : WBC growth factors are generally recommended to reduce the risk of neutropenic fever when the anticipated risk of neutropenic fever for a chemotherapy regimen is approximately ≥20% (ASCO [Smith 2015]).
SUBQ: 250 mcg/m2/day beginning at least 24 hours after chemotherapy administration; continue until ANC >1,500/mm3 for 3 consecutive days (ASCO [Smith 2015]).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling.
There are no dosage adjustments provided in the manufacturer's labeling.
|
Adverse reaction |
Severity |
Sargramostim dosage modification |
|---|---|---|
|
Leukocytosis |
ANC >20,000/mm3 (Acute myeloid leukemia, following induction chemotherapy; allogeneic bone marrow transplantation) |
Interrupt sargramostim or reduce sargramostim dose by 50%. |
|
WBC >50,000/mm3 (Autologous peripheral blood progenitor cell mobilization and collection) |
Reduce sargramostim dose by 50%. | |
|
WBC >50,000/mm3 (Allogeneic bone marrow transplantation) |
Interrupt sargramostim or reduce sargramostim dose by 50%. | |
|
Disease progression or blast cell appearance |
Any (Acute myeloid leukemia, following induction chemotherapy; allogeneic or autologous bone marrow transplantation) |
Immediately discontinue sargramostim. |
|
Hypersensitivity |
Serious allergic reactions |
Manage reaction appropriately and permanently discontinue sargramostim. |
|
Infusion-related reactions |
Acute symptoms or dyspnea during infusion |
Reduce sargramostim infusion rate by 50%. Persistent or worsening symptoms despite rate reduction: Discontinue sargramostim infusion. Subsequent IV infusions following infusion-related reactions may be administered using standard dose schedule with careful monitoring. |
|
Other toxicity (clinically significant) |
Grade 3 or 4 |
Reduce sargramostim dose by 50% or interrupt sargramostim until adverse reaction resolves. |
Refer to adult dosing.
(For additional information see "Sargramostim: Pediatric drug information")
Neutrophil recovery; myeloid reconstitution:
Allogeneic bone marrow transplantation:
Infants ≥5 months and Children <2 years: Limited data available: IV: 250 mcg/m2/day infused over 4 hours once daily; begin on day 0 of the BMT and administer first dose after marrow infusion completed and continue for 21 days; discontinue if ANC >20,000/mm3 (Trigg 2000)
Children ≥2 years and Adolescents: IV: 250 mcg/m2/day infused over 2 hours; begin 2 to 4 hours after the marrow infusion and at least 24 hours after chemotherapy or radiotherapy; do not initiate until the post marrow infusion ANC is <500/mm3 and continue until ANC >1,500/mm3 for 3 consecutive days
If WBC >50,000/mm3 or ANC >20,000/mm3, interrupt treatment or reduce the dose by 50%.
If grade 3 or 4 adverse reactions occur, reduce dose by 50% or temporarily discontinue the dose until the reaction abates.
If blast cells appear or progression of the underlying disease occurs, discontinue treatment.
Autologous bone marrow transplantation:
Children ≥2 years and Adolescents: IV: 250 mcg/m2/day infused over 2 hours; begin 2 to 4 hours after the marrow infusion and at least 24 hours after chemotherapy or radiotherapy; do not initiate until the post marrow infusion ANC is <500/mm3 and continue until ANC >1,500/mm3 for 3 consecutive days. Do not administer within 24 hours before or after chemotherapy or radiation therapy.
Delayed neutrophil recovery or graft failure; allogeneic or autologous bone marrow transplantation: Children ≥2 years and Adolescents: IV: 250 mcg/m2/day infused over 2 hours for 14 days; may repeat 14-day course if engraftment has not occurred after 7 days off sargramostim. If neutrophil recovery still has not occurred after 7 days off sargramostim, a third course of 500 mcg/m2/day for 14 days may be attempted. If there is still no improvement, it is unlikely that further dose escalation will be of benefit.
If WBC >50,000/mm3 or ANC >20,000/mm3, interrupt treatment or reduce the dose by 50%.
If grade 3 or 4 adverse reactions occur, reduce the dose by 50% or temporarily discontinue the dose until the reaction abates.
If blast cells appear or disease progression occurs, discontinue treatment immediately.
Hematopoietic radiation injury syndrome, acute:
Weight-directed dosing: Infants, Children, and Adolescents: Begin as soon as possible after suspected or confirmed exposure to radiation doses >2 gray (Gy); do not delay sargramostim if CBC is not readily available; continue sargramostim until ANC remains >1,000/mm3 for 3 consecutive CBCs (obtain CBCs approximately every 3 days) or ANC exceeds 10,000/mm3 after radiation-induced nadir.
<15 kg: SubQ: 12 mcg/kg once daily
15 to 40 kg: SubQ: 10 mcg/kg once daily
>40 kg: SubQ: 7 mcg/kg once daily
BSA-directed dosing: Limited data available: Children and Adolescents: SubQ: 250 mcg/m2/day; continue until ANC >1,000/mm3 (Waselenko 2004). Note: ASCO guidelines recommend initiating within 24 hours of exposure of a dose ≥2 Gy and/or significant decrease in absolute lymphocyte count, or for anticipated neutropenia <500/mm3 for ≥7 days (ASCO [Smith 2015]).
Neuroblastoma, high-risk: Limited data available: Infants, Children, and Adolescents: SubQ or IV: 250 mcg/m2 once daily for 14 days during cycles 1, 3, and 5, beginning 3 days prior to administration of dinutuximab (each cycle is 28 days) as part of a multi-drug regimen that includes dinutuximab, isotretinoin, and aldesleukin (Gilman 2009; Yu 2010).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling.
There are no dosage adjustments provided in the manufacturer's labeling.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Cardiovascular: Hypertension (34%), edema (13% to 25%), pericardial effusion (4% to 25%), chest pain (15%), peripheral edema (11%), tachycardia (11%)
Central nervous system: Malaise (57%), headache (26%), chills (25%), anxiety (11%), insomnia (11%)
Dermatologic: Skin changes (77%), skin rash (44%), pruritus (23%)
Endocrine & metabolic: Elevated serum glucose (49%), weight loss (37%), decreased serum albumin (36%), hyperglycemia (25%), hypomagnesemia (15%)
Gastrointestinal: Diarrhea (81% to 89%), nausea (58% to 70%), vomiting (46% to 70%), abdominal pain (38%), anorexia (13%), hematemesis (13%), dysphagia (11%), gastrointestinal hemorrhage (11%)
Genitourinary: Urinary tract infection (14%)
Hepatic: Hyperbilirubinemia (30%)
Neuromuscular & skeletal: Asthenia (66%), ostealgia (21%), arthralgia (11% to 21%), myalgia (18%)
Ophthalmic: Retinal hemorrhage (11%)
Renal: Increased serum creatinine (15%)
Respiratory: Pharyngitis (23%), epistaxis (17%), dyspnea (15%)
Miscellaneous: Fever (81%), laboratory test abnormality (58%, metabolic)
1% to 10%:
Immunologic: Antibody development (2%)
Respiratory: Pleural effusion (1%)
<1%, postmarketing, and/or case reports: Anaphylaxis, bone marrow dysplasia, capillary leak syndrome, cardiac disease, decreased serum total protein, eosinophilia, erythema, flushing, hemorrhage (neurocortical events), hypersensitivity reaction, hypotension, hypoxia, increased monocytes, infusion related reaction, injection site reaction, leukocytosis, liver function impairment, pain, prolonged prothrombin time, respiratory distress, supraventricular cardiac arrhythmia, syncope, thromboembolic complications, urticaria, weight gain
History of serious allergic reactions, including anaphylaxis, to human granulocyte-macrophage colony stimulating factor such as sargramostim, yeast-derived products, or any component of the formulation.
Concerns related to adverse effects:
• Cardiovascular effects: Supraventricular arrhythmia has been reported during sargramostim administration, particularly in patients with a prior history of cardiac arrhythmia. These arrhythmias have been reversible following sargramostim discontinuation. Use with caution in patients with preexisting cardiac disease.
• Effusions/capillary leak syndrome: Edema, capillary leak syndrome, pleural and/or pericardial effusion have been reported. Sargramostim may aggravate fluid retention in patients with preexisting pleural and pericardial effusions; however, fluid retention has been shown to be reversible with dosage reduction or discontinuation of sargramostim with or without concomitant use of diuretics. Use with caution in patients with preexisting fluid retention, pulmonary infiltrates, or congestive heart failure.
• Hypersensitivity: Serious allergic and anaphylactic reactions have been reported; use appropriate precautions with parenteral administration of sargramostim in the event of allergic reactions.
• Immunogenicity: Treatment with sargramostim may induce neutralizing anti-drug antibodies. Antibody formation may be related to duration of sargramostim exposure; use sargramostim for the shortest duration necessary.
• Infusion reactions: IV administration of sargramostim may be associated with infusion-related reactions; symptoms may include respiratory distress, hypoxia, flushing, hypotension, syncope, and/or tachycardia following the initial IV infusion in a cycle. Infusion reactions have resolved with symptomatic treatment and generally do not recur with subsequent doses within the same treatment cycle. Observe closely for symptoms during infusion, particularly in patients with preexisting pulmonary disease.
• Leukocytosis: White blood cell counts ≥50,000/mm3 have observed with sargramostim. The decision to reduce the dose or interrupt treatment should be based on the patient's clinical condition. Following cessation of therapy, excessive blood counts return to normal or baseline levels within 3 to 7 days.
Concurrent drug therapy issues:
• Cytotoxic chemotherapy/radiotherapy: Do not administer simultaneously with or within 24 hours preceding/following cytotoxic chemotherapy or radiotherapy (due to the sensitivity of rapidly dividing hematopoietic progenitor cells).
Special populations:
• Pediatric patients: Colony-stimulating factor (CSF) use in pediatric patients is typically directed by clinical pediatric protocols. The ASCO Recommendations for the Use of WBC Growth Factors Clinical Practice Guideline Update states that CSFs may be reasonable as primary prophylaxis in pediatric patients when chemotherapy regimens with a high likelihood of febrile neutropenia are employed. Likewise, secondary CSF prophylaxis should be limited to high-risk patients. In pediatric cancers in which dose-intense chemotherapy (with a survival benefit) is used, CSFs should be given to facilitate chemotherapy administration. CSFs should not be used in the pediatric population for non-relapsed acute lymphoblastic or myeloid leukemia when no infection is present (ASCO [Smith 2015]).
Dosage form specific issues:
• Benzyl alcohol and derivatives: Some dosage forms or diluents may contain benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol with caution in neonates.
Other warnings/precautions:
• Tumor growth factor: May potentially act as a growth factor for any tumor type, particularly myeloid malignancies; caution should be exercised when using in any malignancy with myeloid characteristics.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Injection [preservative free]:
Leukine: 250 mcg (1 ea)
No
Solution (reconstituted) (Leukine Injection)
250 mcg (per each): $370.15
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Sargramostim is administered as a SUBQ injection or IV infusion. Administer at approximately the same time each day.
IV: Infuse over 2 hours, 4 hours or 24 hours (indication specific). An in-line membrane filter should NOT be used for intravenous administration.
SUBQ: Administer subcutaneously into the thigh, abdomen (avoiding waistline and avoiding within 2 inches of navel), or (if a caregiver administers) the outer upper arm; rotate injection sites (injection sites should be at least 1 inch apart from prior injection sites). Do not inject into areas that are tender, bruised, red, or hard; avoid areas with scars or stretch marks. Administer without further dilution.
Parenteral:
IV: Administer as 2-hour, 4-hour, or 24-hour infusion (indication specific). An in-line membrane filter should not be used for intravenous administration. Do not shake solution to avoid foaming.
SubQ: Administer reconstituted solution without further dilution; rotate injection sites; avoiding navel/waistline
Acute myeloid leukemia, following induction chemotherapy: To shorten time to neutrophil recovery and to reduce the incidence of severe, life-threatening, or fatal infections following induction chemotherapy in adults ≥55 years of age with acute myeloid leukemia (AML).
Allogeneic bone marrow transplantation, myeloid reconstitution: Acceleration of myeloid reconstitution in pediatric patients ≥2 years of age and adults undergoing allogeneic bone marrow transplantation from HLA-matched related donors.
Allogeneic or autologous bone marrow transplantation, treatment of delayed neutrophil recovery or graft failure: Treatment of delayed or failed neutrophil recovery in pediatric patients ≥2 years of age and adults who have undergone allogeneic or autologous bone marrow transplantation.
Autologous peripheral blood progenitor cell mobilization and collection: Mobilization of hematopoietic progenitor cells into peripheral blood for collection by leukapheresis in adults with cancer undergoing autologous hematopoietic cell transplantation.
Autologous peripheral blood progenitor cell and bone marrow transplantation: To accelerate myeloid reconstitution following autologous peripheral blood progenitor cell transplantation or bone marrow transplantation in pediatric patients ≥2 years of age and adults with acute lymphoblastic leukemia (ALL), Hodgkin lymphoma (HL), and non-Hodgkin lymphoma (NHL).
Hematopoietic radiation injury syndrome, acute: Treatment to increase survival due to acute exposure to myelosuppressive radiation doses (hematopoietic syndrome of acute radiation syndrome [H-ARS]) in infants, children, adolescents, and adults.
Neuroblastoma, high risk, relapsed or refractory; Primary prophylaxis of neutropenia in patients receiving chemotherapy (outside transplant and AML) or who are at high risk for neutropenic fever
Leukine may be confused with Leukeran, leucovorin
Sargramostim may be confused with efbemalenograstim alfa, eflapegrastim, filgrastim, pegfilgrastim, tbo-filgrastim
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Androgens: Hypertension-Associated Agents may enhance the hypertensive effect of Androgens. Risk C: Monitor therapy
Belotecan: Granulocyte Colony-Stimulating Factors may enhance the neutropenic effect of Belotecan. Management: Do not administer granulocyte colony-stimulating factor (G-CSF) until at least 24 hours after completion of belotecan administration. Monitor neutrophil counts and signs/symptoms of neutropenic fever in patients receiving this combination. Risk D: Consider therapy modification
Betibeglogene Autotemcel: Granulocyte Colony-Stimulating Factors may interact via an unknown mechanism with Betibeglogene Autotemcel. Management: Granulocyte-colony stimulating factor is not recommended for 21 days after betibeglogene autotemcel infusion. Risk X: Avoid combination
Bleomycin: Granulocyte Colony-Stimulating Factors may enhance the adverse/toxic effect of Bleomycin. Specifically, the risk for pulmonary toxicity may be increased. Management: Avoid use of granulocyte colony-stimulating factors 24 hours before (14 days for pegfilgrastim) and 24 hours after the last dose of bleomycin. Risk D: Consider therapy modification
Corticosteroids (Systemic): May enhance the therapeutic effect of Sargramostim. Specifically, corticosteroids may enhance the myeloproliferative effects of sargramostim. Risk C: Monitor therapy
CycloPHOSphamide: May enhance the adverse/toxic effect of Sargramostim. Specifically, the risk of pulmonary toxicity may be enhanced. Risk C: Monitor therapy
Exagamglogene Autotemcel: Granulocyte Colony-Stimulating Factors may enhance the adverse/toxic effect of Exagamglogene Autotemcel. Risk X: Avoid combination
Lithium: Sargramostim may enhance the adverse/toxic effect of Lithium. Specifically, the myeloproliferative effects may be increased. Risk C: Monitor therapy
Lovotibeglogene Autotemcel: Granulocyte Colony-Stimulating Factors may enhance the adverse/toxic effect of Lovotibeglogene Autotemcel. Risk X: Avoid combination
Solriamfetol: May enhance the hypertensive effect of Hypertension-Associated Agents. Risk C: Monitor therapy
Tisagenlecleucel: Granulocyte Colony-Stimulating Factors may enhance the adverse/toxic effect of Tisagenlecleucel. Risk X: Avoid combination
Topotecan: Granulocyte Colony-Stimulating Factors may enhance the adverse/toxic effect of Topotecan. Specifically, the risk for the development of interstitial lung disease may be increased. Granulocyte Colony-Stimulating Factors may enhance the myelosuppressive effect of Topotecan. Management: Avoid use of granulocyte colony-stimulating factors 24 hours before (14 days for pegfilgrastim) and 24 hours after the last dose of topotecan. Additionally, monitor patients closely for the development of interstitial lung disease with this combination. Risk D: Consider therapy modification
Data regarding use in pregnant patients is limited. Some dosage forms may contain benzyl alcohol (avoid in pregnant patients due to association with gasping syndrome in premature infants); if use is necessary during pregnancy, lyophilized powder reconstituted with preservative-free sterile water for injection is recommended.
It is not known if sargramostim is present in breast milk. Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended during treatment and for at least 2 weeks after the last sargramostim dose.
CBC with differential (twice weekly during treatment); when monitoring for hematopoietic radiation injury syndrome, obtain CBCs approximately every 3 days. Monitor vital signs. Monitor hydration status and weight during treatment. Monitor for signs/symptoms of hypersensitivity or infusion-related reactions; monitor carefully if reinitiating following a prior infusion reaction.
Sargramostim is a colony stimulating growth factor which stimulates proliferation, differentiation, and functional activity of neutrophils, eosinophils, monocytes, and macrophages.
Onset of action: Increase in WBC in 7 to 14 days
Duration: WBCs return to baseline within 1 to 2 weeks of discontinuing drug
Distribution: IV: 96.8 L
Bioavailability: SubQ: 75% (compared to IV)
Half-life elimination:
Children 6 months to 15 years: IV: Median: 1.6 hours; range: 0.9 to 2.5 hours; SubQ: Median: 2.3 hours (0.3 to 3.8 hours) (Stute 1995)
Adults: IV: 3.84 hours; SubQ: 1.4 hours
Time to peak, serum: IV: During or immediately after infusion; SubQ: 2.5 to 4 hours
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