No

Colony Stimulating Factor

Treatment of anemia associated with chronic renal failure, including patients on dialysis (end-stage renal disease) and patients not on dialysis

Treatment of anemia related to zidovudine therapy in HIV-infected patients; in patients when the endogenous erythropoietin level is less than or equal to 500 mU/mL and the dose of zidovudine is less than or equal to 4200 mg/week

Treatment of anemia in cancer patients on chemotherapy; in patients with nonmyeloid malignancies where anemia is caused by the effect of the concomitantly administered chemotherapy; to decrease the need for transfusions in patients who will be receiving chemotherapy for a minimum of 2 months

Reduction of allogeneic block transfusion in surgery patients scheduled to undergo elective, noncardiac, nonvascular surgery

C

Clinical effect on the fetus: Epoetin alfa has been shown to have adverse effects in rats when given in doses 5X the human dose. There are no adequate and well-controlled studies in pregnant women. Epoetin alfa should be used only if potential benefit justifies the potential risk to the fetus.

Known hypersensitivity to albumin (human) or mammalian cell-derived products; uncontrolled hypertension

Use with caution in patients with porphyria, hypertension, or a history of seizures; prior to and during therapy, iron stores must be evaluated. It is recommended that the epoetin dose be decreased if the hematocrit increase exceeds 4 points in any 2-week period.

Serum ferritin >100 ng/dL

Transferrin saturation (serum iron/iron binding capacity x 100) of 20% to 30%

Iron supplementation (usual oral dosing of 325 mg 2-3 times/day) should be given during therapy to provide for increased requirements during expansion of the red cell mass secondary to marrow stimulation by EPO unless iron stores are already in excess

For patients with endogenous serum EPO levels which are inappropriately low for hemoglobin level, documentation of the serum EPO level will help indicate which patients may benefit from EPO therapy. Serum EPO levels can be ordered routinely from Clinical Chemistry (red top serum separator tube). Refer to "Reference Range" for information on interpretation of EPO levels.

Listed are factors limiting response to epoetin alfa, and their mechanism:

• Iron deficiency: Limits hemoglobin synthesis
• Blood loss/hemolysis: Counteracts epoetin alfa-stimulated erythropoiesis
• Infection/inflammation: Inhibits iron transfer from storage to bone marrow; suppresses erythropoiesis through activated macrophages
• Aluminum overload: Inhibits iron incorporation into heme protein
• Bone marrow replacement; hyperparathyroidism; metastatic, neoplastic: Limits bone marrow volume
• Folic acid/vitamin B₁₂ deficiency: Limits hemoglobin synthesis
• Patient compliance: Self-administered epoetin alfa or iron therapy

Increased mortality has occurred when aggressive dosing is used in CHF or anginal patients undergoing hemodialysis. An Amgen-funded study determined that when patients were targeted for a hematocrit of 42% versus a less aggressive 30%, mortality was higher (35% versus 29%).

>10%:

Cardiovascular: Hypertension

Central nervous system: Fatigue, headache, fever

1% to 10%:

Cardiovascular: Edema, chest pain

Gastrointestinal: Nausea, vomiting, diarrhea

Hematologic: Clotted access

Neuromuscular & skeletal: Arthralgias, asthenia

<1%: Myocardial infarction, CVA/TIA, rash, hypersensitivity reactions

Symptoms of overdose include erythrocytosis

Adequate airway and other supportive measures and agents for treating anaphylaxis should be present when I.V. drug is given

Vials should be stored at 2°C to 8°C (36°F to 46°F); do not freeze or shake; single-use vials are stable 2 weeks at room temperature and multidose vials are stable for 1 week at room temperature

Single-dose 1 mL vial contains no preservative: Use one dose per vial; do not re-enter vial; discard unused portions

Multidose 2 mL vial contains preservative; store at 2°C to 8°C after initial entry and between doses; discard 21 days after initial entry

For minimal dilution: Mix with bacteriostatic 0.9% sodium chloride, containing 20 mL of 0.9% sodium chloride and benzyl alcohol as the bacteriostatic agent; dilutions of 1:10 and 1:20 (1 part to epoetin:19 parts sodium chloride) are stable for 18 hours at room temperature; results showed no loss of epoetin alfa after a 1:20 dilution; 250 mcg/mL albumin remaining after a 1:10 dilution of formulated epoetin alfa should be sufficient to prevent it from binding to commonly encountered containers

Induces erythropoiesis by stimulating the division and differentiation of committed erythroid progenitor cells; induces the release of reticulocytes from the bone marrow into the bloodstream, where they mature to erythrocytes. There is a dose response relationship with this effect. This results in an increase in reticulocyte counts followed by a rise in hematocrit and hemoglobin levels.

Onset of action: Several days

Peak effect: 2-3 weeks

Distribution: V_d: 9 L; rapid in the plasma compartment; majority of drug is taken up by the liver, kidneys, and bone marrow

Metabolism: Some metabolic degradation does occur

Bioavailability: S.C.: ~21% to 31%; intraperitoneal epoetin in a few patients demonstrated a bioavailability of only 3%

Half-life: Circulating: 4-13 hours in patients with chronic renal failure; 20% shorter in patients with normal renal function

Time to peak serum concentrations: S.C.: 2-8 hours

Elimination: Small amounts recovered in the urine; majority hepatically eliminated; 10% excreted unchanged in the urine of normal volunteers

Chronic renal failure patients: I.V., S.C.:

Initial dose: 50-100 units/kg 3 times/week

Reduce dose by 25 units/kg when

1) hematocrit approaches 36% or

2) when hematocrit increases >4 points in any 2-week period

Increase dose if hematocrit does not increase by 5-6 points after 8 weeks of therapy and hematocrit is below suggested target range

Suggested target hematocrit range: 30% to 36%

Maintenance dose: Individualize to target range

Dialysis patients: Median dose: 75 units/kg 3 times/week

Nondialysis patients: Doses of 75-150 units/kg

Zidovudine-treated, HIV-infected patients: Patients with erythropoietin levels >500 mU/mL are unlikely to respond

Initial dose: I.V., S.C.: 100 units/kg 3 times/week for 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 hematocrit 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 patients have not responded satisfactorily to a 300 unit/kg dose 3 times/week, it is unlikely that they will respond to higher doses

Stop dose if hematocrit exceeds 40% and resume treatment at a 25% dose reduction when hematocrit drops to 36%

Cancer patients on chemotherapy: Treatment of patients with erythropoietin levels >200 mU/mL is not recommended

Initial dose: S.C.: 150 units/kg 3 times/week

Dose adjustment: If response is not satisfactory in terms of reducing transfusion requirement or increasing hematocrit after 8 weeks of therapy, the dose may be increased up to 300 units/kg 3 times/week. If patients do not respond, it is unlikely that they will respond to higher doses.

If hematocrit exceeds 40%, hold the dose until it falls to 36% and reduce the dose by 25% when treatment is resumed

Surgery patients: Prior to initiating treatment, obtain a hemoglobin to establish that is is >10 mg/dL or less than or equal to 13 mg/dL

Initial dose: S.C.: 300 units/kg/day for 10 days before surgery, on the day of surgery, and for 4 days after surgery

Alternative dose: S.C.: 600 units/kg in once weekly doses (21, 14, and 7 days before surgery) plus a fourth dose on the day of surgery

Dilute with an equal volume of normal saline and infuse over 1-3 minutes; it may be administered into the venous line at the end of the dialysis procedure

Careful monitoring of blood pressure is indicated; problems with hypertension have been noted especially in renal failure patients treated with rHuEPO. Other patients are less likely to develop this complication.

Suggested tests to be monitored and their frequency:

• Hematocrit*/hemoglobin: Monitor 2 x/week during initial phase, then 2-4 x/month during maintenance phase
• Blood pressure: Monitor 3 x/week during initial phase and during maintenance phase
• Serum ferritin: Monitor monthly during initial phase, and quarterly during maintenance phase
• Transferrin saturation: Monitor monthly during initial phase, and quarterly during maintenance phase
• Serum chemistries including CBC with differential, creatinine, blood urea nitrogen, potassium, phosphorous: Monitor regularly per routine during initial and maintenance phases

*Hematocrit should be determined twice weekly until stabilization within the target range (30% to 36%), and twice weekly for at least 2-6 weeks after a dose increase.

Hematocrit should be determined twice weekly until stabilization within the target range (30% to 36%), and twice weekly for at least 2 to 6 weeks after a dose increase.

Guidelines should be based on the following figure or published literature

Zidovudine-treated HIV patients: Available evidence indicates patients with endogenous serum erythropoietin levels >500 mU/mL are unlikely to respond

Cancer chemotherapy patients: Treatment of patients with endogenous serum erythropoietin levels >200 mU/mL is not recommended

Sedation is common; may cause dizziness

None reported

No information available to require special precautions

No effects or complications reported

You will require frequent blood tests to determine appropriate dosage. Do not take other medications, vitamin or iron supplements, or make significant changes in your diet without consulting prescriber. Report signs or symptoms of edema (eg, swollen extremities, difficulty breathing, rapid weight gain), onset of severe headache, acute back pain, chest pain, or muscular tremors or seizure activity. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to be pregnant. Consult prescriber if breast-feeding.

Dilute with an equal volume of normal saline and infuse over 1-3 minutes; may be administered into the venous line at the end of the dialysis procedure

1 mL single-dose vials: Preservative-free solution

2000 units/mL

3000 units/mL

4000 units/mL

10,000 units/mL

20,000 units/mL

40,000 units/mL

2 mL multidose vials: Preserved solution: 10,000 units/mL

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