| Correction of anemia associated with CRF: Initial: 0.45 mcg/kg (IV, SQ) once weekly. Dosage should be titrated to limit increases in hemoglobin to <1 g/dL over any 2-week interval, with a target concentration of <12 g/dL. Maintenance: Titrated to hematologic response. Some patients may require doses <0.45 mcg/kg once weekly. Selected patients may be managed by administering SQ doses every 2 weeks.
Note: In patients receiving epoetin alfa 2-3 times per week, darbepoetin alfa is administered once weekly. In patients who are receiving epoetin alfa once weekly, darbepoetin should be administered once every 2 weeks.
Dosage adjustment: Goal: Dose should be adjusted to achieve and maintain a target hemoglobin not to exceed 12 g/dL.
Correction of anemia associated with cancer patients receiving chemotherapy: Initial: 2.25 mcg/kg SQ once weekly. Adjust dose as follows to achieve and maintain a target hemoglobin:
Darbepoetin's T1/2 is approximately 3 times that of epoetin alfa.
| Anemia: (Renal failure): Initial dose: 50-100 units/kg IV/SC 3 x/week. Titration: Reduce dose by 25% when hemoglobin approaches 12 g/dL or when hemoglobin increases 1 g/dL in any 2-week period. Increase dose by 25% if hemoglobin does not increase by 2 g/dL after 8 weeks of therapy and hemoglobin is below suggested target range; suggested target hematocrit range: 10-12 g/dL. Maintenance dose: Individualize to target range.
AZT-treated, HIV infected patients: 100 units/kg IV/SC 3 times/week x 8 weeks. Increase dose by 50-100 units/kg 3 times/week if response is not satisfactory in terms of reducing transfusion requirements or increasing hemoglobin after 8 weeks of therapy. Evaluate response every 4-8 weeks thereafter and adjust the dose accordingly by 50-100 units/kg increments 3 times/week. If patient has not responded satisfactorily to a 300 unit/kg dose 3 times/week, a response to higher doses is unlikely. Stop dose if hemoglobin exceeds 13 g/dl and resume treatment at a 25% dose reduction when hemoglobin drops to 12 g/dl.
Cancer patients on chemotherapy (Treatment of patients with erythropoietin levels >200 mU/mL is not recommended). 150 units/kg SC 3 times/week or 40,000 units once weekly. Dose adjustment: If response is not satisfactory after a sufficient period of evaluation (8 weeks of 3 times/week and 4 weeks of once weekly therapy), the dose may be increased every 4 weeks (or longer) up to 300 units/kg 3 times/week, or when dosed weekly, increased all at once to 60,000 units weekly. If patient does not respond, a response to higher doses is unlikely.
Surgery patients: Prior to initiating treatment, obtain a hemoglobin to establish that is >10 mg/dL or 13 mg/dL: Initial dose: 300 units/kg/day SC x 10 days before surgery, on the day of surgery, and for 4 days after surgery. Alternative dose: 600 units/kg in once weekly doses (21, 14, and 7 days before surgery) plus a fourth dose on the day of surgery.
| CLINICAL PHARMACOLOGY
Colony-stimulating factors are glycoproteins which act on hematopoietic cells by binding to specific cell surface receptors and stimulating proliferation‚ differentiation commitment‚ and some end-cell functional activation.
Endogenous G-CSF is a lineage specific colony-stimulating factor which is produced by monocytes‚ fibroblasts, and endothelial cells. G-CSF regulates the production of neutrophils within the bone marrow and affects neutrophil progenitor proliferation differentiation and selected end-cell functional activation (including enhanced phagocytic ability, priming of the cellular metabolism associated with respiratory burst‚ antibody dependent killing, and the increased expression of some functions associated with cell surface antigens). G-CSF is not species specific and has been shown to have minimal direct in vivo or in vitro effects on the production of hematopoietic cell types other than the neutrophil lineage.
Myelosuppressive therapy: 5 mcg/kg/day - doses may be increased by 5 mcg/kg according to the duration and severity of the neutropenia.
Bone marrow transplantation: 5-10 mcg/kg/day - doses may be increased by 5 mcg/kg according to the duration and severity of neutropenia; recommended steps based on neutrophil response:
When ANC >1000/mm3 for 3 consecutive days: Reduce filgrastim dose to 5 mcg/kg/day
Peripheral blood progenitor cell (PBPC) collection: 10 mcg/kg/day or 5-8 mcg/kg twice daily in donors. The optimal timing and duration of growth factor stimulation has not been determined.
Severe chronic neutropenia:
Injection, solution [preservative free]: 600 mcg/mL (0.5 mL, 0.8 mL) [prefilled Singleject® syringe; contains sodium 0.035 mg/mL and sorbitol]
Comparative Effects G-CSF vs GM-CSF
Initial U.S. Approval: 2015
Mechanism of Action: Colony-stimulating factors are glycoproteins which act on hematopoietic cells by binding to specific cell surface receptors and stimulating proliferation‚ differentiation commitment‚ and some end-cell functional activation.
Endogenous G-CSF is a lineage-specific colony-stimulating factor that is produced by monocytes‚ fibroblasts, and endothelial cells. G-CSF regulates the production of neutrophils within the bone marrow and affects neutrophil progenitor proliferation‚ differentiation, and selected end-cell functions (including enhanced phagocytic ability‚ priming of the cellular metabolism associated with respiratory burst‚ antibody-dependent killing, and the increased expression of some cell surface antigens). G-CSF is not species-specific and has been shown to have minimal direct in vivo or in vitro effects on the production or activity of hematopoietic cell types other than the neutrophil lineage.
INDICATIONS AND USAGE:
1.2 Patients with Acute Myeloid Leukemia Receiving Induction or Consolidation Chemotherapy
1.3 Patients with Cancer Undergoing Bone Marrow Transplantation
1.4 Patients Undergoing Autologous Peripheral Blood Progenitor Cell Collection and Therapy
1.5 Patients with Severe Chronic Neutropenia
| BOXED WARNING
Allergic Reactions Including Anaphylaxis
Neumega has caused allergic or hypersensitivity reactions, including anaphylaxis. Administration of Neumega should be permanently discontinued in any patient who develops an allergic or hypersensitivity reaction
The primary hematopoietic activity of Neumega is stimulation of megakaryocytopoiesis and thrombopoiesis. Neumega has shown potent thrombopoietic activity in animal models of compromised hematopoiesis, including moderately to severely myelosuppressed mice and nonhuman primates. In these models, Neumega improved platelet nadirs and accelerated platelet recoveries compared to controls.
Preclinical trials have shown that mature megakaryocytes which develop during in vivo treatment with Neumega are ultrastructurally normal. Platelets produced in response to Neumega were morphologically and functionally normal and possessed a normal life span.
IL-11 has also been shown to have non-hematopoietic activities in animals including the regulation of intestinal epithelium growth (enhanced healing of gastrointestinal lesions), the inhibition of adipogenesis, the induction of acute phase protein synthesis, inhibition of pro-inflammatory cytokine production by macrophages, and the stimulation of osteoclastogenesis and neurogenesis. Non-hematopoietic pathologic changes observed in animals include fibrosis of tendons and joint capsules, periosteal thickening, papilledema, and embryotoxicity
INDICATIONS AND USAGE
Note: The manufacturer states that, until efficacy/toxicity parameters are established, the use of oprelvekin in pediatric patients (particularly those <12 years of age) should be restricted to use in controlled clinical trials.
Adults: 50 mcg/kg once daily for 10-21 days (until postnadir platelet count >/= 50,000 cells/uL)
| CLINICAL PHARMACOLOGY
Both Filgrastim and pegfilgrastim are Colony Stimulating Factors that act on hematopoietic cells by binding to specific cell surface receptors thereby stimulating proliferation, differentiation, commitment, and end cell functional activation. Studies on cellular proliferation, receptor binding, and neutrophil function demonstrate that Filgrastim and pegfilgrastim have the same mechanism of action. Pegfilgrastim has reduced renal clearance and prolonged persistence in vivo as compared to Filgrastim.
INDICATIONS AND USAGE
Adult Respiratory Distress Syndrome (ARDS)
Sickle Cell Disease
| INDICATIONS AND USAGE
OMONTYS is an erythropoiesis-stimulating agent (ESA) indicated for the treatment of anemia due to chronic kidney disease (CKD) in adult patients on dialysis.
Limitations of Use
In patients with CKD not on dialysis .
DOSAGE AND ADMINISTRATION
DOSAGE FORMS AND STRENGTHS
Single use pre-filled syringes (preservative-free) 1 mg/0.5 mL, 2 mg/0.5 mL, 3 mg/0.5 mL, 4 mg/0.5 mL, 5 mg/0.5 mL, and 6 mg/0.5 mL
Multiple use vials (with preservative) 10 mg/mL and 20 mg/2 mL
WARNINGS AND PRECAUTIONS
Use caution in patients with coexistent cardiovascular disease and stroke.
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