LEUKINE
Clinical safety rating
cautionComprehensive 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. |
| Molecular Weight | 15500 |
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 | Limited human data; animal studies show fetal harm. Use only if maternal benefit outweighs risk. |
| 2nd trimester | Limited human data; may cause fetal harm due to immunomodulatory effects. Avoid unless necessary. |
| 3rd trimester | Limited human data; may cause fetal harm. Use only if clearly needed. |
Clinical note
Comprehensive clinical and safety monograph for LEUKINE (LEUKINE).
| Placental transfer | Molecular weight suggests potential transfer; however, specific human data on placental transfer is lacking. Animal studies indicate minimal transfer, but extrapolation is uncertain. |
| Breastfeeding | It is not known if sargramostim is excreted in human milk. Because many drugs are excreted, caution should be exercised when administered to a nursing woman. Consider the benefits of breastfeeding, the risk of infant drug exposure, and the risk of maternal condition. |
| Lactation Rating | L3 (Moderately Safe) |
| 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. |
| 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. |
■ 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 yeast-derived productsConcurrent administration with myelosuppressive chemotherapy or radiation therapyLeukemic blasts in bone marrow or peripheral blood (except for AML induction)
| 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 |
| Food/Dietary | No known food interactions. No dietary restrictions required. |
| Clinical Pearls | Monitor for fluid retention and capillary leak syndrome. Obtain CBC with differential at baseline and twice weekly during therapy. Do not administer within 24 hours before or after chemotherapy. Reconstitute with 1 mL sterile water for injection; do not shake. Store reconstituted solution at 2-8°C and use within 6 hours. |
| Patient Advice | Report any signs of allergic reaction, such as rash, hives, or difficulty breathing immediately. · Notify your healthcare provider if you experience swelling, rapid weight gain, or shortness of breath. · Keep all appointments for blood tests to monitor your white blood cell counts. · Do not receive this medication within 24 hours before or after chemotherapy. · Store the medication in the refrigerator; do not freeze. Discard any unused portion after 6 hours. |
Loading safety data…