Skip to Content
Top of Page: How to talk to a doctor about advanced ovarian cancer >>

Sargramostim

Pronunciation

(sar GRAM oh stim)

Index Terms

  • GM-CSF
  • GMCSF
  • Granulocyte-Macrophage Colony Stimulating Factor
  • Prokine
  • Recombinant Granulocyte-Macrophage Colony Stimulating Factor
  • rhuGM-CSF

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Slideshow: Donate Life: What You Need To Know About Organ Donorship

Solution, Injection:

Leukine: 500 mcg/mL (1 mL [DSC]) [contains benzyl alcohol]

Solution Reconstituted, Intravenous [preservative free]:

Leukine: 250 mcg (1 ea)

Brand Names: U.S.

  • Leukine

Pharmacologic Category

  • Colony Stimulating Factor
  • Hematopoietic Agent

Pharmacology

Stimulates proliferation, differentiation and functional activity of neutrophils, eosinophils, monocytes, and macrophages.

Time to Peak

Serum: SubQ: 1 to 3 hours

Duration of Action

WBCs return to baseline within 1 to 2 weeks of discontinuing drug

Half-Life Elimination

IV: ~60 minutes; SubQ: ~2.7 hours

Use: Labeled Indications

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

Use: Unlabeled

Primary prophylaxis of neutropenia in patients receiving chemotherapy (outside transplant and AML) or who are at high risk for neutropenic fever

Treatment of radiation-induced myelosuppression of the bone marrow

Contraindications

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

Dosage

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 >1500/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: Adults: 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: Adults: 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 >1500 /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: Adults: 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: Adults: 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 >1500/mm3 for 3 consecutive days.

Primary prophylaxis of neutropenia in patients receiving chemotherapy (outside transplant and AML) or who are at high risk for neutropenic fever (off-label use): Adults: 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 >2000 to 3000/mm3 (Smith, 2006).

Treatment of radiation-induced myelosuppression of the bone marrow (off-label use): Adults: SubQ: 250 mcg/m2/day; continue until ANC >1000/mm3 (Smith, 2006; Waselenko, 2004).

Dosage adjustment in renal impairment: There are no dosage adjustments provided in the manufacturer’s labeling.

Dosage adjustment in hepatic impairment: There are no dosage adjustments provided in the manufacturer’s labeling.

Reconstitution

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).

Administration

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.

Compatibility

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.

Storage

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.

Drug Interactions

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

Test Interactions

May interfere with bone imaging studies; increased hematopoietic activity of the bone marrow may appear as transient positive bone imaging changes

Adverse Reactions

>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

Warnings/Precautions

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.

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:

• 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.

Monitoring Parameters

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

Pregnancy Risk Factor

C

Pregnancy Considerations

Animal reproduction studies have not been conducted.

Patient Education

• 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, dyspepsia, osteodynia, arthralgia, lack of appetite, stomatitis, alopecia, or weight loss. Have patient report immediately to prescriber signs of hepatic impairment, tachycardia, arrhythmia, dyspnea, excessive weight gain, edema of extremities, severe dizziness, syncope, flushing, considerable diarrhea, edema of extremities, extremity discoloration, or painful extremities, significant headache, chills, intolerable asthenia, ecchymosis, hemorrhaging, hematemesis, melena, angina, or paresthesia (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 healthcare 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.

Hide