Important Safety Considerations
Leukine® is contraindicated in patients with excessive leukemic myeloid blasts in bone marrow or peripheral blood (≥ 10%), in patients with known hypersensitivity to GM-CSF, yeast derived products or any component of Leukine, and for concomitant use with chemotherapy and radiotherapy. View additional Important Safety Information. View Indications.

Dosing and Administration

Leukine® liquid contains benzyl alcohol and should not be administered to neonates.

Recommended dosing for adults 55 years and older with AML following induction chemotherapy1

Dosage 250 mcg/m2/day by IV infusion over a 4-hour period
Initiate 4 days following completion of chemotherapy (approximately day 11)
Continue until ANC of >1500 cells/mm3 is achieved for 3 consecutive days (or a maximum of 42 days)*
Adjust or interrupt If ANC >20,000 cells/mm3, reduce dose by half or interrupt treatment

*A landmark study demonstrated that an ANC of 1500 cells/mm3 is the critical level for neutrophils above which there is no additional protection against infection.9

Recommended dosing for mobilization of peripheral blood progenitor cells (PBPC)1

Dosage 250 mcg/m2/day IV or SC
Continue until Day 5 or protocol-specified targets have been achieved
Adjust If WBC >50,000 cells/mm3, reduce dose by half

Recommended dosing for post-PBPC transplantation1

Dosage 250 mcg/m2/day IV or SC
Initiate Immediately after PBPC infusion
Continue until ANC of >1500 cells/mm3 is achieved for 3 consecutive days (or a maximum of 42 days)*

Recommended dosing for autologous bone marrow transplantation (AuBMT) or allogeneic BMT (AlloBMT)1

Dosage 250 mcg/m2/day IV
Initiate
  • 2 to 4 hours after bone marrow infusion and >24 hours after the last dose of chemotherapy or radiotherapy
  • When ANC falls below 500 cells/mm3
Continue until ANC of >1500 cells/mm3 is achieved for 3 consecutive days
Adjust or interrupt If a severe adverse reaction occurs or if ANC >20,000 cells/mm3, reduce dose by half or interrupt treatment

Recommended dosing for BMT failure or engraftment delay1

Dosage 250 mcg/m2/day IV
Initiate Immediately
Duration
  • 14 days
  • If engraftment has not occurred after 7 days off therapy, successive course(s) may be given as needed (14 days on/7 days off)
Adjust or interrupt If a severe adverse reaction occurs or if ANC >20,000 cells/mm3, reduce dose by half or interrupt treatment

  • Leukine should not be administered simultaneously with cytotoxic chemotherapy or radiotherapy or within 24 hours preceding or following chemotherapy or radiotherapy1

Leukine is available in 2 formulations

  • Liquid: 500 mcg/mL sterile solution in multi-use vial that may be stored for up to 20 days after vial has been entered
  • Lyophilized powder: 250 mcg in single-use vial ready for sterile reconstitution
  • Both formulations are suitable for IV infusion and SC injection

Indication

Leukine® is indicated for the following uses: (i) following induction chemotherapy in older adult patients with acute myelogenous leukemia (AML) to shorten time to neutrophil recovery; (ii) for mobilization and following transplantation of autologous peripheral blood progenitor cells; (iii) for myeloid reconstitution after autologous or allogeneic bone marrow transplantation (BMT); (iv) for use in bone marrow transplantation failure or engraftment delay.

Important Safety Considerations

  • Leukine is contraindicated in patients with excessive leukemic myeloid blasts in bone marrow or peripheral blood (≥10%); in patients with known hypersensitivity to GM-CSF, yeast-derived products, or any component of Leukine; and for concomitant use with chemotherapy and radiotherapy.
  • Serious allergic or anaphylactic reactions have been reported with Leukine. If any serious allergic or anaphylactic reactions occur, Leukine therapy should be immediately discontinued and appropriate therapy initiated.
  • Liquid solutions containing benzyl alcohol (including liquid Leukine) or lyophilized Leukine reconstituted with Bacteriostatic Water for Injection, USP (0.9% benzyl alcohol) should not be administered to neonates.
  • Leukine should be used with caution and monitored in patients with preexisting fluid retention, pulmonary infiltrates, or congestive heart failure, respiratory symptoms or disease; cardiac symptoms or disease; and renal or hepatic dysfunction.
  • Edema, capillary leak syndrome, pleural and/or pericardial effusion, sequestration of granulocytes in the pulmonary circulation, and dyspnea have been reported in patients after Leukine administration. Occasional transient supraventricular arrhythmia has been reported during Leukine administration. Leukine has induced the elevation of serum creatinine or bilirubin and hepatic enzymes in some patients. Monitoring of renal and hepatic function in patients with preexisting renal or hepatic dysfunction is recommended at least every other week during Leukine administration.
  • Adverse events occurring in >10% of patients receiving Leukine in controlled clinical trials and reported in a higher frequency than placebo were: in AML patients – (fever, skin reactions, metabolic disturbances, nausea, vomiting, weight-loss, edema, anorexia); in Autologous BMT patients – (asthenia, malaise, diarrhea, rash, peripheral edema, urinary tract disorder); and in Allogeneic BMT patients – (abdominal pain, chills, chest pain, diarrhea, nausea, vomiting, hematemesis, dysphagia, GI hemorrhage, pruritus, bone pain, arthralgia, eye hemorrhage, hypertension, tachycardia, bilirubinemia, hyperglycemia, increased creatinine, hypomagnesemia, edema, pharyngitis, epistaxis, dyspnea, insomnia, anxiety, high BUN, and high cholesterol).
  • If ANC > 20,000 cells/mm3 or if platelet counts > 500,000/mm3, LEUKINE administration should be interrupted or the dose reduced by half. Twice weekly monitoring of CBC with differential should be performed.
  • Leukine therapy should be discontinued if disease progression is detected during treatment.

Please see full Prescribing Information.

To report suspected adverse events, contact Genzyme Corporation at 1-888-4RX-LEUKINE or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

References

  1. LEUKINE® (sargramostim) [package insert]. Genzyme Corporation 2009.

  2. Data on file. Genzyme Corporation.

  3. Rowe JM, Rubin A, Mazza JJ, et al. Incidence of infections in adult patients (> 55 years) with acute myeloid leukemia treated with yeast-derived GM-CSF (sargramostim): results of a double-blind prospective study by the Eastern Cooperative Oncology Group. In: Hiddemann W, et al, eds. Acute Leukemias V: Experimental Approaches and Management of Refractory Diseases. Berlin, Germany: Springer-Verlag; 1996:178-184.

  4. Rowe JM. Treatment of acute myeloid leukemia with cytokines: effect on duration of neutropenia and response to infections. Clin Infect Dis. 1998;26:1290-1294.

  5. Nemunaitis J, Rosenfeld CS, Ash R, et al. Phase III randomized, double-blind placebo-controlled trial of rhGM-CSF following allogeneic bone marrow transplantation. Bone Marrow Transplant. 1995;15:949-54.

  6. Nemunaitis J, Rabinowe SN, Singer JW, et al. Recombinant granulocyte-macrophage colony-stimulating factor after autologous bone marrow transplantation for lymphoid cancer. N Engl J Med. 1991;324:1773-1778.

  7. Bennett CL, Golub R, Waters TM, Tallman MS, Rowe JM. Economic analyses of phase III cooperative cancer group clinical trials: are they feasible? Cancer Invest. 1997;15:227-236.

  8. Luce BR, Singer JW, Weschler JM, et al. Recombinant human granulocyte-macrophage colony-stimulating factor after autologous bone marrow transplantation for lymphoid cancer: an economic analysis of a randomised, double-blind, placebo-controlled trial. Pharmacoeconomics. 1994;6:42-48.

  9. Bodey GP, Buckley M, Sathe YS, Freireich EJ. Quantitative relationships between circulating leukocytes and infection in patients with acute leukemia. Ann Intern Med. 1966;64:328-340.