(sar GRAM oh stim)
Acute myeloid leukemia (AML; following induction chemotherapy): To shorten time to neutrophil recovery and to reduce the incidence of severe and life-threatening infections and infections resulting in death following induction chemotherapy in older adults ( ≥55 years of age)
Bone marrow transplant (allogeneic or autologous) failure or engraftment delay: For graft failure or engraftment delay in patients who have undergone allogeneic or autologous bone marrow transplantation, to prolong survival (survival benefit may be greater in patients with autologous bone marrow transplant failure or engraftment delay, no previous total body irradiation, malignancy other than leukemia, or multiple organ failure score ≤2)
Myeloid reconstitution after allogeneic bone marrow transplantation: To accelerate myeloid recovery in patients undergoing allogeneic bone marrow transplant from HLA-matched related donors (safe and effective in accelerating myeloid engraftment, reducing the incidence of bacteremia and other culture-positive infections, and shortening the median hospitalization duration)
Myeloid reconstitution after autologous bone marrow transplantation: To accelerate myeloid recovery following transplantation in non-Hodgkin lymphoma (NHL), acute lymphoblastic leukemia (ALL), Hodgkin lymphoma patients undergoing autologous bone marrow transplant (safe and effective in accelerating myeloid engraftment, reducing the median duration of antibiotic administration, reducing the median duration of infectious episodes, and shortening the median hospitalization duration)
Peripheral stem cell transplantation (autologous), mobilization and post-transplant: Mobilization of hematopoietic progenitor cells for collection by leukapheresis (increases the number of progenitor cells capable of engraftment and may lead to more rapid engraftment); to accelerate myeloid reconstitution following peripheral blood progenitor cell transplantation
Hypersensitivity to sargramostim, yeast-derived products, or any component of the formulation; concurrent (24 hours preceding/following) use with myelosuppressive chemotherapy or radiation therapy; patients with excessive ( ≥10%) leukemic myeloid blasts in bone marrow or peripheral blood
Note: May round the dose to the nearest vial size (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. If WBC >50,000/mm3 and/or ANC >20,000/mm3, interrupt treatment or reduce the dose by 50%.
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
Discontinue sargramostim immediately if leukemic regrowth occurs. If a severe adverse reaction occurs, reduce the dose by 50% or temporarily discontinue the dose until the reaction abates.
Bone marrow transplantation (allogeneic or autologous) failure or engraftment delay: 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 engraftment 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 a severe adverse reaction occurs, reduce the dose by 50% or temporarily discontinue the dose until the reaction abates
If blast cells appear or disease progression occurs, discontinue treatment
If WBC >50,000/mm3 and/or ANC >20,000 cells/mm3, interrupt treatment or reduce the dose by 50%.
Myeloid reconstitution after allogeneic or autologous bone marrow transplantation: IV: 250 mcg/m2/day (infused over 2 hours), begin 2 to 4 hours after the marrow infusion and ≥24 hours after chemotherapy or radiotherapy, when the post marrow infusion ANC is <500/mm3, and continue until ANC >1,500/mm3 for 3 consecutive days. If WBC >50,000/mm3 and/or ANC >20,000/mm3, interrupt treatment or reduce the dose by 50%.
If a severe adverse reaction occurs, 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
Peripheral stem cell transplantation (autologous), mobilization: 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. If WBC >50,000/mm3, reduce the dose by 50%.
Note: The optimal schedule for peripheral blood progenitor cell collection has not been established (usually begun by day 5 and performed daily until protocol specified targets are achieved). If adequate numbers of progenitor cells are not collected, consider other mobilization therapy.
Peripheral stem cell transplantation (autologous), post-transplant: 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.
Hematopoietic radiation injury syndrome, acute (off-label use): 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 gray (Gy) and/or significant decrease in absolute lymphocyte count, or for anticipated neutropenia <500/mm3 for ≥7 days (Smith 2015).
Primary prophylaxis of neutropenia in patients receiving chemotherapy (outside transplant and AML) or who are at high risk for neutropenic fever (off-label use): SubQ: 250 mcg/m2/day (may round to the nearest vial size [Ozer 2000]) beginning at least 24 hours after chemotherapy administration; continue until ANC >1,500/mm3 for 3 consecutive days (Smith 2015).
Refer to adult dosing.
Hematopoietic radiation injury syndrome, acute (off-label use): Children and Adolescents: 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 gray (Gy) and/or significant decrease in absolute lymphocyte count, or for anticipated neutropenia <500/mm3 for ≥7 days (Smith 2015).
There are no dosage adjustments provided in the manufacturer 's labeling.
There are no dosage adjustments provided in the manufacturer 's labeling.
Powder for injection: May be reconstituted with 1 mL of preservative free SWFI or bacteriostatic water for injection. Direct the diluent toward the side of the vial and gently swirl to reconstitute; do not shake. Do not mix the contents of vials which have been reconstituted with different diluents.
SubQ: May be administered without further dilution.
IV: Further dilution with NS is required. If the final sargramostim concentration is <10 mcg/mL, 1 mg of human albumin per 1 mL of NS should be added (eg, add 1 mL of 5% human albumin per 50 mL of NS).
Sargramostim is administered as a subcutaneous injection or intravenous infusion.
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 undiluted; rotate injection sites, avoiding navel/waistline.
Store intact vials at 2 � �C to 8 � �C (36 � �F to 46 � �F); do not freeze. Do not shake.
Solution for injection: May be stored for up to 20 days at 2 � �C to 8 � �C (36 � �F to 46 � �F) once the vial has been entered. Discard remaining solution after 20 days.
Powder for injection: Preparations made with SWFI should be administered as soon as possible, and discarded within 6 hours of reconstitution. Solutions reconstituted with bacteriostatic water may be stored for up to 20 days at 2 � �C to 8 � �C (36 � �F to 46 � �F); do not freeze. When combining previously reconstituted solutions with freshly reconstituted solutions, administer within 6 hours following preparation; the contents of vials reconstituted with different diluents should not be mixed together.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution, Injection:
Leukine: 500 mcg/mL (1 mL [DSC]) [contains benzyl alcohol]
Solution Reconstituted, Intravenous [preservative free]:
Leukine: 250 mcg (1 ea)
Stable in NS, SWFI, bacteriostatic water.
Y-site administration: Incompatible with acyclovir, ampicillin, chlorpromazine, haloperidol, hydrocortisone sodium phosphate, hydrocortisone sodium succinate, hydromorphone, hydroxyzine, imipenem/cilastatin, lorazepam, methylprednisolone sodium succinate, mitomycin, morphine, nalbuphine, ondansetron, piperacillin, sodium bicarbonate, tobramycin.
Bleomycin: Sargramostim may enhance the adverse/toxic effect of Bleomycin. Specifically, the risk for pulmonary toxicity may be increased. Monitor therapy
Cyclophosphamide: May enhance the adverse/toxic effect of Sargramostim. Specifically, the risk of pulmonary toxicity may be enhanced. Monitor therapy
CBC with differential (twice weekly during treatment), renal/liver function tests (at least every 2 weeks in patients displaying renal or hepatic dysfunction prior to treatment initiation); pulmonary function; vital signs; hydration status; weight
May interfere with bone imaging studies; increased hematopoietic activity of the bone marrow may appear as transient positive bone imaging changes
>10%:
Cardiovascular: Hypertension (34%), edema (13% to 25%), pericardial effusion (4% to 25%), thrombosis (19%), chest pain (15%), peripheral edema (11%), tachycardia (11%)
Central nervous system: Malaise (57%), headache (26%), chills (25%), anxiety (11%), insomnia (11%)
Dermatologic: Skin rash (44% to 77%), pruritus (23%)
Endocrine & metabolic: Weight loss (37%), hyperglycemia (25%), hypercholesterolemia (17%), hypomagnesemia (15%)
Gastrointestinal: Diarrhea (81% to 89%), nausea (58% to 70%), vomiting (46% to 70%), gastric ulcer (50%), abdominal pain (38%), anorexia (13%), hematemesis (13%), dysphagia (11%), gastrointestinal hemorrhage (11%)
Hepatic: Hyperbilirubinemia (30%)
Neuromuscular & skeletal: Weakness (66%), ostealgia (21%), arthralgia (11% to 21%), myalgia (18%)
Ophthalmic: Retinal hemorrhage (11%)
Renal: Increased blood urea nitrogen (23%), increased serum creatinine (15%)
Respiratory: Pharyngitis (23%), epistaxis (17%), dyspnea (15%)
Miscellaneous: Fever (81%)
1% to 10%:
Immunologic: Antibody development (2%)
Respiratory: Pleural effusion (1%)
<1% (Limited to important or life-threatening): Anaphylaxis, capillary leak syndrome, cardiac arrhythmia, eosinophilia, hypoxia, leukocytosis, liver function impairment (transient), pericarditis, prolonged prothrombin time, respiratory distress, rigors, sore throat, supraventricular cardiac arrhythmia, syncope, thrombocythemia, thrombophlebitis
Concerns related to adverse effects:
- Allergic reactions: Anaphylaxis or other serious allergic reactions have been reported; discontinue immediately and initiate appropriate therapy if a serious allergic or anaphylactic reaction occurs.
- First-dose effect: A "first-dose effect " �, characterized by respiratory distress, hypoxia, flushing, hypotension, syncope, and/or tachycardia, may occur (rarely) with the first dose of a cycle and resolve with appropriate symptomatic treatment; symptoms do not usually occur with subsequent doses within that cycle.
- Fluid retention: Edema, capillary leak syndrome, pleural and/or pericardial effusion have been reported; 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 pre-existing fluid retention, pulmonary infiltrates, or congestive heart failure; may exacerbate fluid retention.
- Hematologic effects: If there is a rapid increase in blood counts (ANC >20,000/mm3, WBC >50,000/mm3, or platelets >500,000/mm3), decrease the dose by 50% or discontinue therapy. Excessive blood counts should fall to normal within 3 to 7 days after the discontinuation of therapy. Monitor CBC with differential twice weekly during treatment.
- Pulmonary symptoms: Sequestration of granulocytes in pulmonary circulation and dyspnea have been reported; monitor respiratory symptoms during and following IV infusion. Decrease infusion rate by 50% if dyspnea occurs; discontinue the infusion if dyspnea persists despite reduction in the rate of administration. Subsequent doses may be administered at the standard rate with careful monitoring. Use with caution in patients with hypoxia or pre-existing pulmonary disease.
Disease-related concerns:
- Cardiac disease: Use with caution in patients with pre-existing cardiac disease. Reversible transient supraventricular arrhythmias have been reported, especially in patients with a history of arrhythmias.
- Hepatic impairment: Use with caution in patients with hepatic impairment; hyperbilirubinemia and elevated transaminases have been observed in this patient population. Monitor hepatic function at least every other week in patients with history of hepatic dysfunction.
- Renal impairment: Use with caution in patients with renal impairment; serum creatinine elevations have been observed in this patient population. Monitor renal function at least every other week in patients with history of renal dysfunction.
Concurrent drug therapy issues:
- Cytotoxic chemotherapy/radiotherapy: Simultaneous administration, or administration 24 hours preceding/following cytotoxic chemotherapy or radiotherapy is contraindicated due to the sensitivity of rapidly dividing hematopoietic progenitor cells.
Special populations:
- Elderly patients: The American Society of Clinical Oncology (ASCO) Recommendations for the Use of WBC Growth Factors Clinical Practice Guideline Update recommend that prophylactic colony-stimulating factors be used in patients ≥65 years with diffuse aggressive lymphoma treated with curative chemotherapy (eg, rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone), especially if patients have comorbid conditions (Smith 2015).
- Pediatric patients: Colony-stimulating factor (CSF) use in pediatric patients is typically directed by clinical pediatric protocols. The American Society of Clinical Oncology (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 (Smith 2015).
Dosage form specific issues:
- Benzyl alcohol and derivatives: Some dosage forms 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. See manufacturer 's labeling.
Other warnings/precautions:
- Appropriate use: CSFs should not be routinely used in the treatment of established neutropenic fever. Colony-stimulating factors may be considered in cancer patients with febrile neutropenia who are at high risk for infection-associated complications or who have prognostic factors indicative of a poor clinical outcome (eg, prolonged and severe neutropenia, age >65 years, hypotension, pneumonia, sepsis syndrome, presence of invasive fungal infection, uncontrolled primary disease, hospitalization at the time of fever development) (Freifeld 2011; Smith 2006). CSFs should not be routinely used for patients with neutropenia who are afebrile. Dose-dense regimens that require CSFs should only be used within the context of a clinical trial or if supported by convincing evidence (Smith 2015).
- Efficacy: Limited response to sargramostim may be seen in patients who have received bone marrow purged by chemical agents which do not preserve an adequate number of responsive hematopoietic progenitors (eg, <1.2 x 104/kg progenitors). In patients receiving autologous bone marrow transplant, response to sargramostim may be limited if extensive radiotherapy to the abdomen or chest or multiple myelotoxic agents were administered prior to transplant.
- 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. Discontinue use if disease progression occurs during treatment.
C
Animal reproduction studies have not been conducted.
Stimulates proliferation, differentiation and functional activity of neutrophils, eosinophils, monocytes, and macrophages.
Increase in WBC in 7 to 14 days
Serum: SubQ: 1 to 3 hours
WBCs return to baseline within 1 to 2 weeks of discontinuing drug
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: ~60 minutes; SubQ: ~2.7 hours
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience injection site irritation, insomnia, anxiety, nausea, vomiting, abdominal pain, bone pain, joint pain, lack of appetite, mouth sores, hair loss, or weight loss. Have patient report immediately to prescriber signs of liver problems (dark urine, feeling tired, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin or eyes), signs of DVT (edema, warmth, numbness, change in color, or pain in the extremities); tachycardia; arrhythmia; shortness of breath; excessive weight gain; swelling of arms or legs; severe dizziness; passing out; flushing; severe diarrhea; severe headache; chills; severe loss of strength and energy; bruising; bleeding; vomiting blood; black, tarry, or bloody stools; angina; or burning or numbness feeling (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.