Dosing and uses of Gmcsf, Leukine (sargramostim)
Adult dosage forms and strengths
injectable solution
- 500mcg/mL
powder for injection
- 250mcg/vial
Myloid Reconstitution Following Allogeneic or Autologous Bone Marrow Transplant
250 mcg/m²/day IV over 2-4 hours after bone marrow infusion & not less than 24 hours after last dose of chemo or radiation; hold Leukine until post-BMT ANC is <500 cells/m³ & continue until ANC>1500 cells/m³ for 3 consecutive days
Administer 2-4hr after bone marrow infusion and >24hr after chemotherapy or radiotherapy
If severe adverse reaction occurs, can reduce dose by 50% or temporarily discontinue until reaction ceases
Post-chemo Neutrophil Recovery in AML
250 mcg/m²/day IV over 4 hours beginning on approximately day 11 or 4 days after completion of induction treatment
If day 10 bone marrow is hypoplastic with <5% blasts; continue until ANC>1500 cells/m³ or for a max of 42 days
Stem Cell Mobilization
250 mcg/m²/day IV over 24 hours or as a daily SC dose during collection; reduce dose by 50% if WBC >50,000 cells/mm³
Post-stem Cell Transplant
250 mcg/m²/day IV over 24 hours or as a daily SC dose immediately following transplant & until ANC>1500 cells/m³ for 3 consecutive days
MDS (Off-label)
15-500 mcg/m² IV infusion qDay over 1-12 hours OR 30-500 mcg/m² continuous infusion over 24 hours
Aplastic Anemia (Off-label)
15-480 mcg/m² IV infusion qDay over 1-12 hours OR 120-500 mcg/m² continuous infusion over 24 hours
Cystic Fibrosis (Orphan)
Orphan indication sponsor
- DrugRecure Aps; Cobis Building, 2200 Copenhagen N; Denmark
Other Indications & Uses
Acceleration of myeloid recovery in patients requiring bone marrow transplant; hematopoietic stem cell mobilization for leukapharesis; peripheral blood progenitor cell transplantation; induction chemotherapy in AML
Off-label: Increased WBCs in myelodysplastic syndromes, AIDS patients receiving zidovudine, myelosuppressive chemotherapy
Pediatric dosage forms and strengths
powder for injection
- 250mcg/vial
Myloid Reconstitution Following Allogeneic or Autologous Bone Marrow Transplant
Safety & efficacy not eatablished; no special adverse effects reported at dosages similar to adult
250 mcg/m²/day IV over 2-4 hours after bone marrow infusion & not less than 24 hours after last dose of chemo or radiation; hold Leukine until post-BMT ANC is <500 cells/m³ & continue until ANC>1500 cells/m³ for 3 consecutive days
Administer 2-4hr after bone marrow infusion and >24hr after chemotherapy or radiotherapy
If severe adverse reaction occurs, can reduce dose by 50% or temporarily discontinue until reaction ceases
Solution has benzyl alcohol; do not administer to neonates (benzyl alcohol associated with gasping syndrome in neonates)
If severe adverse reaction occurs, can reduce dose by 50% or temporarily discontinue until reaction ceases
Geriatric dosage forms and strengths
Myloid Reconstitution Following Allogeneic or Autologous Bone Marrow Transplant
250 mcg/m²/day IV over 2-4 hours after bone marrow infusion & not less than 24 hours after last dose of chemo or radiation; hold Leukine until post-BMT ANC is <500 cells/m³ & continue until ANC>1500 cells/m³ for 3 consecutive days
Administer 2-4hr after bone marrow infusion and >24hr after chemotherapy or radiotherapy
If severe adverse reaction occurs, can reduce dose by 50% or temporarily discontinue until reaction ceases
Post-chemo Neutrophil Recovery in AML
250 mcg/m²/day IV over 4 hours beginning on approximately day 11 or 4 days after completion of induction treatment
If day 10 bone marrow is hypoplastic with <5% blasts; continue until ANC>1500 cells/m³ or for a max of 42 days
Stem Cell Mobilization
250 mcg/m²/day IV over 24 hours or as a daily SC dose during collection; reduce dose by 50% if WBC >50,000 cells/mm³
Post-stem Cell Transplant
250 mcg/m²/day IV over 24 hours or as a daily SC dose immediately following transplant & until ANC>1500 cells/m³ for 3 consecutive days
MDS (Off-label)
15-500 mcg/m² IV infusion qDay over 1-12 hours OR 30-500 mcg/m² continuous infusion over 24 hours
Aplastic Anemia (Off-label)
15-480 mcg/m² IV infusion qDay over 1-12 hours OR 120-500 mcg/m² continuous infusion over 24 hours
Gmcsf, Leukine (sargramostim) adverse (side) effects
>10%
Autologous BMt
- Abdominal pain (89%)
- Diarrhea (89%)
- Asthenia (66%)
- Malaise (57%)
- Rash (44%)
- Chest pain (11%)
- Peripheral edema (11%)
Acute myelogenous leukemia
- Fever (81%)
- Skin reaction (77%)
- Metabolic disease (58%)
- Nausea (58%)
- Vomiting (46%)
- Weight loss (37%)
Diarrhea (allogenic BMT 81%)
Nausea (allogenic BMT 70%)
Vomiting (allogenic BMT 70%)
Abdominal pain (allogenic BMT 38%)
Hyperbilirubinemia (allogenic BMT 30%)
Rigor (allogenic BMT 25%)
Cardiac dysrhythmia (BMT graft failure 25%)
Pericardial effusion (BMT graft failure 25%)
Pruritis (allogenic BMT 23%)
Increase serum BUN (allogenic BMT 23%)
Pharyngitis (allogenic BMT 23%)
Bone pain (allogenic BMT 21%)
Myalgia (BMT graft failure 18%)
Hypercholesterolemia (allogenic BMT 17%)
Hypomagnesemia (allogenic BMT 15%)
Chest pain (allogenic BMT 15%)
Hematemesis (allogenic BMT 13%)
GI hemorrhage (allogenic BMT 11%)
Intraocular hemorrhage (allogenic BMT 11%)
Dysphagia (allogenic BMT 11%)
Arthralgia (allogenic BMT 11%)
1-10%
Cardiac dysrhythmia (autologous BMT 4%)
Pericardial effusion (autologous BMT 4%)
<1%
Capillary leak syndrome
Frequency not defined
Anorexia
Fever
Malaise
Cerebral hemorrhage
Stomatitis
Elevated BUN and cholesteroL
Renal failure
Sepsis
Warnings
Contraindications
Hypersensitivity to drug or yeast proteins
>10% leukemic myeloid blasts in bone marrow or peripheral blood
Do not administer within 24 hr preceding or following chemotherapy or radiotherapy
Cautions
Caution in fluid retention, pulmonary infiltrates, CHF, lung disease, cardiac disease, hypoxia, hepatic/renal impairment; conditions may worsen
Solution should NOT be administered to neonates due to presence of benzyl alcohol in the formulation ant its association with "gasping syndrome"
Discontinue immediately if blast cells appear or disease progression occurs
Reformulated liquid devoid of sodium EDTA now available
Pregnancy and lactation
Pregnancy category: C
Lactation: Not known if excreted in breast milk
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Gmcsf, Leukine (sargramostim)
Mechanism of action
Recombinant granulocyte macrophage colony stimulating factor; acts on hematopoietic cells to stimulate proliferation & differentiation particularly into neutrophils, monocytes/macrophages & myeloid-derived dendritic cells & some end cell function activity
Pharmacokinetics
Half-life elimination: 60 min (IV); 2.7hr (SC)
Peak plasma time: 1-3hr (SC)
Clearance: 420 mL/min/m²
Duration: WBC are at baseline within 1 week of stopping the therapy
Onset of action: 7-14 days (increase in WBC)
