LEUKINE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for LEUKINE (LEUKINE).
Granulocyte-macrophage colony-stimulating factor (GM-CSF) that stimulates proliferation, differentiation, and functional activity of neutrophils, monocytes, macrophages, and dendritic cells.
| Metabolism | Primarily cleared by receptor-mediated internalization and degradation; not extensively metabolized by hepatic enzymes. |
| Excretion | Renal: <5% unchanged; hepatically metabolized, with metabolites and parent drug eliminated primarily via biliary/fecal route (estimated >90% in animal studies). |
| Half-life | Terminal half-life: approximately 2.6 hours (range 1.3-4.5 hours) after subcutaneous administration; its short half-life requires daily dosing for sustained hematopoietic effect. |
| Protein binding | Approximately 50-75% bound; primary binding proteins albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Volume of distribution: approximately 1.0-1.5 L/kg; distributed widely into tissues including bone marrow. |
| Bioavailability | Subcutaneous: approximately 50%; bioavailability after intramuscular administration has not been established. |
| Onset of Action | Subcutaneous: neutrophil count increase begins within 24-48 hours after first dose; intravenous: similar onset, with peak effect at 3-4 hours post-infusion. |
| Duration of Action | Neutrophil counts return to baseline within 48-96 hours after discontinuation; clinical effects on hematopoiesis persist for duration of therapy. |
250 mcg/m2/day IV over 2 hours on days 1-21 of a 28-day cycle for AML; 250 mcg/m2/day SC daily for 21 days for hematopoietic reconstitution after BMT; 250 mcg/m2/day SC daily for 10 days for mobilization of peripheral blood progenitor cells; 5 mcg/kg/day SC for 14 days for neutropenia due to ganciclovir in CMV retinitis.
| Dosage form | VIAL |
| Renal impairment | No specific dose adjustment provided; use with caution in severe renal impairment (CrCl < 30 mL/min) due to potential accumulation. |
| Liver impairment | No specific dose adjustment provided; monitor hepatic function in patients with preexisting hepatic impairment. |
| Pediatric use | Safety and efficacy not established in pediatric patients; no specific dosing guidelines. |
| Geriatric use | No specific dose adjustment recommended; monitor closely for adverse effects. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for LEUKINE (LEUKINE).
| Breastfeeding | It is not known whether LEUKINE is excreted into human milk. Many drugs are excreted in human milk, and because of the potential for serious adverse reactions in nursing infants from LEUKINE, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. No M/P ratio available. |
| Teratogenic Risk | LEUKINE (sargramostim) is a recombinant granulocyte-macrophage colony-stimulating factor. No adequate and well-controlled studies in pregnant women. In animal studies, no evidence of fetal harm was observed at doses up to 6 mg/kg/day in rats and rabbits. However, because animal reproduction studies are not always predictive of human response, LEUKINE should be used during pregnancy only if clearly needed. No known specific fetal risks by trimester, but theoretical risk due to potential for stimulating growth of hematopoietic cells in the fetus. |
■ FDA Black Box Warning
WARNING: Risk of respiratory distress syndrome, capillary leak syndrome, and fluid retention; increased risk of death in patients receiving concurrent chemotherapy or radiation therapy for non-myeloid malignancies.
| Serious Effects |
["Hypersensitivity to GM-CSF or any component","Concurrent chemotherapy or radiation therapy to the bone marrow (in the setting of bone marrow transplantation)","Leukemic blasts in blood or bone marrow (>10%)"]
| Precautions | ["Fluid retention and capillary leak syndrome","Respiratory symptoms: dyspnea, pleural effusion","Supraventricular arrhythmias","Bone pain","Allergic reactions","Increased risk of progression of myelodysplasia or leukemia","Monitor for blasts in peripheral blood"] |
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| Fetal Monitoring | Monitor maternal complete blood count (CBC) with differential periodically to assess response and detect leukocytosis. Monitor for signs of fluid retention (e.g., weight gain, edema, pulmonary symptoms) as LEUKINE can cause fluid retention. In pregnant women, monitor fetal growth and well-being via ultrasound as clinically indicated. Monitor for hypersensitivity reactions including rash, injection site reactions, and dyspnea. |
| Fertility Effects | No specific studies on fertility effects in humans. In animal studies, no adverse effects on fertility were observed at doses up to 6 mg/kg/day. Based on mechanism of action, no known impact on fertility, but data are limited. |