Professional Drug Information > Darbepoetin Alfa

Darbepoetin Alfa (Systemic)

VA CLASSIFICATION
Primary: BL400

Commonly used brand name(s): Aranesp.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).



Category:


Antianemic—

Indications

Note: Bracketed information in the Indications section refers to uses that are not included in the U.S. product labeling.

Accepted

Anemia associated with chronic renal failure (treatment)—Darbepoetin alfa is indicated for the treatment of anemia associated with chronic renal failure, including patients on dialysis and patients not on dialysis.^{01}{14}

Anemia associated with chemotherapy in cancer patients (treatment)¹—Darbepoetin alfa is indicated for the treatment of anemia in adults with nonmyeloid malignancies in which the anemia is due to the effect of concomitantly administered chemotherapy.
^{{04}{05}{06}{07}{08}{14}}

¹ Not included in Canadian product labeling.

Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Molecular weight—
    37,000 daltons ^{01}


pH
    Albumin solution: 6 ± 0.3 ^{01}.
    Polysorbate solution: 6.2 ± 0.2 ^{01}.

Mechanism of action/Effect:

Darbepoetin alfa is an erythropoiesis stimulating protein closely related to erythropoietin that is produced by recombinant DNA technology. Darbepoetin alfa is a 165-amino acid protein that differs from recombinant human erythropoietin in containing 5 N-linked oligosaccharide chains, whereas recombinant human erythropoietin contains 3.^{01}

Darbepoetin alfa stimulates erythropoiesis by the same mechanism as endogenous erythropoietin. A primary growth factor for erythroid development, erythropoietin is produced in the kidney and released into the bloodstream in response to hypoxia. In responding to hypoxia, erythropoietin interacts with progenitor stem cells to increase red blood cell production. Production of endogenous erythropoietin is impaired in patients with chronic renal failure (CRF), and erythropoietin deficiency is the primary cause of their anemia. Increased hemoglobin levels are not generally observed until 2 to 6 weeks after initiating treatment. ^{01}

In patients with cancer receiving concomitant chemotherapy, the etiology of anemia is multifactorial. ^{08}

Absorption:

Bioavailability of darbepoetin alfa when given as a subcutaneous injection in chronic renal failure (CRF) patients is approximately 37%^{01}{08}

Half-life:
Terminal—

   • CRF patients: Intravenous administration— 21 hours^{01}{08}
   • CRF patients: Subcutaneous administration— 49 hours^{01}{08}
Distribution

   • CRF patients: Intravenous administration— 1.4 hours^{01}{08}

Onset of action:

Increased hemoglobin levels are not generally observed until 2 to 6 weeks after the initiation of treatment.^{01}

Time to peak concentration:

CRF patients: Single subcutaneous dose—34 hours (range: 24 to 72 hours)^{01}{08}

Cancer patients: Single subcutaneous dose—90 hours (range: 71 to 123 hours) ^{08}


Precautions to Consider

Carcinogenicity

The carcinogenic potential of darbepoetin alfa has not been evaluated in long-term animal studies^{01}.

Tumorigenicity

In toxicity studies of approximately 6 months duration in rats and dogs, no tumorigenic or unexpected mitogenic responses were observed in any tissue type^{01}.

Mutagenicity

Darbepoetin alfa was negative in the in vitro bacterial and CHO cell assays to detect mutagenicity and in the in vivo mouse micronucleus assay to detect clastogenicity^{01}.

Pregnancy/Reproduction
Fertility—
When administered intravenously to male and female rats prior to and during mating, reproductive performance, fertility, and sperm assessment parameters were not affected at any doses evaluated (up to 10 mcg per kg per dose, administered 3 times weekly). An increase in postimplantation fetal loss was seen at doses equal to or greater than 0.5 mcg per kg per dose, administered 3 times weekly (3-fold higher than the recommended weekly starting human dose)^{01}.

Pregnancy—
Adequate and well-controlled studies in pregnant women have not been done. Darbepoetin alfa should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus^{01}.

When darbepoetin alfa was administered intravenously to rats and rabbits during gestation, no evidence of a direct embryotoxic, fetotoxic, or teratogenic outcome was observed at doses up to 20 mcg per kg per day (40 fold higher than the recommended weekly starting dose)^{02}. The only adverse effect observed was a slight reduction in fetal weight, which occurred at doses causing exaggerated pharmacological effects in the dams (1 mcg per kg per day and higher). No deleterious effects on uterine implantation were seen in either species. No significant placental transfer of darbepoetin alfa was observed in rats^{01}.

Intravenous injection of darbepoetin alfa to female rats every other day from day 6 of gestation through day 23 of lactation at doses of 2.5 mcg per kg per dose and higher resulted in offspring (F1 generation) with decreased body weights, which correlated with a low incidence of deaths, delayed eye opening and delayed preputial separation. No adverse effects were seen in the F2 offspring^{01}.

FDA Pregnancy Category C ^{01}

Breast-feeding

It is not known whether darbepoetin alfa is distributed into human breast milk^{01}.

Pediatrics

No information is available on the relationship of age to the effects of darbepoetin alfa in the pediatric population. Safety and efficacy have not been established^{01}.


Geriatrics


Appropriate studies performed to date have not demonstrated geriatrics-specific problems that would limit the usefulness of darbepoetin alfa in the elderly. ^{01} During clinical trials of chronic renal failure (CRF) patients receiving darbepoetin alfa, 42% of the patient population was age 65 and over and 15% were 75 and over. During clinical trials of cancer patients receiving darbepoetin alfa and concomitant chemotherapy, 45% were age 65 and over and 14% were 75 and over. ^{08} No overall differences in safety and efficacy were observed between these patients and younger patients, but greater sensitivity of some older individuals cannot be ruled out ^{02}.


Laboratory value alterations
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

With physiology/laboratory test values
Blood pressure    (may be increased, possibly to hypertensive levels^{01})


Serum ferritin or
serum transferrin saturation    (may be decreased during administration of darbepoetin alfa.^{01})


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Except under special circumstances, this medication should not be used when the following medical problems exist:
» Hypersensitivity to darbepoetin alfa or any of the excipients especially albumin ^{08}
» Hypertension, uncontrolled    (may be exacerbated, especially during the early phase of treatment or when the hemoglobin is increasing; initiation of therapy should be delayed until blood pressure is adequately controlled^{01})


Risk-benefit should be considered when the following medical problems exist
Aluminum toxicity, severe or^{01}
Bone marrow fibrosis or^{01}
Folic acid deficiency or^{01}
Hemolysis or^{01}
Infection or^{01}
Inflammation or^{01}
Malignancy or^{01}
Occult blood loss or^{01}
Osteofibrosis cystica or^{01}
Vitamin B₁₂ deficiency^{01}    (may cause failure of response to darbepoetin alfa therapy)


» Cardiovascular system abnormalities    ( darbepoetin alfa may increase the risk of cardiovascular events in patients with CRF; the higher risk of cardiovascular events may be associated with higher hemoglobin and/or higher rates of rise of hemoglobin^{01})


Hematologic disorders, such as: ^{01}
Hemolytic anemia or
Porphyria or
Sickle cell anemia or
Thalassemia    (the safety and efficacy of darbepoetin alfa have not been established in patients with underlying hematologic diseases ^{01})


Hypertension, controlled    (blood pressure may rise during early stages of treatment with darbepoetin alfa requiring initiation or intensification of antihypertensive therapy.^{01})



Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):

» Blood pressure determinations    (recommended prior to initiation of therapy and at frequent intervals during treatment;^{01} hypertensive encephalopathy and seizures have been observed in patients with CRF treated with darbepoetin alfa^{01})


Fluid and electrolyte balance
» Hemoglobin    (After initiation of darbepoetin alfa therapy, the hemoglobin should be determined weekly until it has stabilized and the maintenance dose has been established.^{01} A recommended target level of 12 grams per dL should not be exceeded. ^{08}; After a dose adjustment, the hemoglobin should be determined weekly for at least 4 weeks until it has been determined that the hemoglobin has stabilized in response to the dose change; hemoglobin should then be monitored at regular intervals. It is recommended that the dose of darbepoetin alfa be decreased if the hemoglobin increase exceeds 1 gram per dL in any 2 week period, because of the association of excessive rate of rise of hemoglobin with cardiovascular events^{01})


» Iron status, including:
Serum ferritin and
Serum transferrin saturation    ( evaluation recommended before and during treatment; supplemental iron therapy is recommended for all patients whose serum ferritin is below 100 mcg per L or whose serum transferrin saturation is below 20%^{01})


» Neurologic status    (during the first several months of therapy, monitor patient for premonitory symptoms of seizures. In clinical trials seizures were reported in patients with chronic renal failure.^{01}While the relationship between seizures and the rate of rise of hemoglobin is uncertain, it is recommended that the dose of darbepoetin alfa be decreased if the hemoglobin increase exceeds 1 gram per dL in any 2 week period^{02})


» Renal function    (due to a potential reduction in dialysis efficiency, close monitoring is recommended in patients with renal function impairment to determine the need for initiating or increasing dialysis, and additionally, predialysis patients may be more responsive to the effect of^{02}darbepoetin alfa administration.^{01})






Side/Adverse Effects

Note: Products formulated with albumin carry an extremely remote risk for transmission of viral diseases, and theoretically, the Creutzfeldt-Jakob disease^{01}.


Note: There is a potential for immunogenicity with darbepoetin alfa administration. During clinical trials, high titer antibodies to darbepoetin alfa were not detected, but assay sensitivity may have been inadequate to reliably detect lower titers^{01}.


Note: Pure red cell aplasia has been observed in patients treated with recombinant erythropoietins and has been reported predominantly in patients with chronic renal failure. The contribution of darbepoetin alfa to the development of pure red cell aplasia is unclear. Darbepoetin alfa should be discontinued in any patient with evidence of pure red cell aplasia and should be evaluated for the presence of binding and neutralizing antibodies to darbepoetin alfa, native erythropoietin, and any other recombinant erythropoietin administered to the patient.^{08}{12}

The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Some of the side effects listed below are typically associated with chronic renal failure, or recognized complications of dialysis, and may not necessarily be attributable to darbepoetin alfa therapy.

Those indicating need for medical attention
Incidence more frequent
    
Abscess (accumulation of pus; swollen, red, tender area of infection; fever )^{01}
    
angina pectoris (arm, back or jaw pain; chest pain or discomfort; chest tightness or heaviness; fast or irregular heartbeat; shortness of breath; sweating; nausea)^{01}
    
bacteremia (rapid breathing; chills; fever; abdominal pain; nausea; diarrhea )^{01}
    
bronchitis (cough producing mucus; difficulty breathing; shortness of breath; tightness in chest; wheezing)^{01}
    
cardiac arrest (stopping of heart; unconsciousness)^{01}
    
cardiac arrhythmias (dizziness; fainting; fast, slow, or irregular heartbeat; lightheadedness; pounding or rapid pulse)
    
chest pain, unspecified ^{01}
    
congestive heart failure ( chest pain; decreased urine output; dilated neck veins; extreme fatigue; irregular breathing; irregular heartbeat; shortness of breath; swelling of face, fingers, feet, or lower legs; tightness in chest; troubled breathing; weight gain; wheezing)^{01}
    
dyspnea (shortness of breath; difficult or labored breathing; tightness in chest; wheezing)^{01}
    
edema, centralized (swelling)—disease state may be a contributing factor^{08}
    
edema, peripheral (swelling of hands, ankles, feet, or lower legs)^{01}
    
fluid overload (decrease in amount of urine; noisy, rattling breathing; shortness of breath; swelling of fingers, hands, feet, or lower legs; troubled breathing at rest; weight gain)^{01}
    
hemorrhage, access ^{01}
    
hypertension (blurred vision; dizziness; headache; pounding in the ears; slow or fast heartbeat)— disease state may be a contributing factor^{08}{01}
    
hypotension (blurred vision; confusion; dizziness, faintness, or lightheadedness when getting up from a lying or sitting position; sudden sweating; unusual tiredness or weakness )^{01}
    
infection, access^{01}
    
peritonitis (abdominal or stomach pain; chills; nausea or vomiting)^{01}
    
pneumonia (chest pain; cough; fever or chills; shortness of breath; troubled breathing; tightness in chest; wheezing)^{01}
    
sepsis (chills; fever; fast heartbeat)^{01}
    
thrombosis, vascular access- (including thrombophlebitis, thrombophlebitis deep, thrombosis venous, thrombosis venous deep, thromboembolism and thrombosis ) (tenderness, pain, swelling, warmth, skin discoloration, and prominent superficial veins over affected area)— disease state may be a contributing factor.^{08}{01}

Incidence less frequent
    
Convulsions (including grand mal and local convulsions) (seizures )—disease state may be a contributing factor^{08}
    
pulmonary embolism (anxiety; chest pain; cough; fainting; fast heartbeat; sudden shortness of breath or troubled breathing; dizziness or lightheadedness )—disease state may be a contributing factor^{08}
    
myocardial infarction, acute ( chest pain or discomfort; pain or discomfort in arms, jaw, back or neck; shortness of breath; nausea; sweating; vomiting )—disease state may be a contributing factor^{08}
    
stroke (confusion; difficulty in speaking; slow speech; inability to speak; inability to move arms, legs, or facial muscles; double vision; headache )
    
transient ischemic attack ( confusion; numbness or tingling in face, arms or legs; trouble speaking, thinking or walking; headache)<sup>{01}

{01}</sup>Incidence rare
    
Allergic reaction (skin rash; and urticaria^{01})
Note: If a serious allergic or anaphylactic reaction occurs, darbepoetin alfa should be immediately and permanently discontinued ^{08}





Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
    
Abdominal pain ^{01}
    
arthralgia (pain in joints; muscle pain or stiffness; difficulty in moving)^{01}
    
asthenia (lack or loss of strength )^{01}
    
back pain ^{01}
    
constipation —disease state may be a contributing factor^{01}{08}
    
cough ^{01}
    
dizziness ^{01}
    
diarrhea ^{01}
    
fatigue ^{01}
    
fever ^{01}
    
headache ^{01}
    
influenza-like symptoms (chills; cough; diarrhea; fever; general feeling of discomfort or illness; headache; joint pain; loss of appetite; muscle aches and pains; nausea; runny nose; shivering; sore throat; sweating; trouble sleeping; unusual tiredness or weakness; vomiting)^{01}
    
injection site pain ^{01}
    
limb pain ^{01}
    
myalgia (muscle ache or pain)^{01}
    
nausea ^{01}
    
pruritus (itching skin)^{01}
    
rash —disease state may be a contributing factor^{08}
    
upper respiratory infection (cough; fever; sneezing; or sore throat)
    
vomiting ^{01}

Incidence less frequent
    
Dehydration (confusion; decreased urination; dizziness; dry mouth; fainting; increase in heart rate; lightheadedness; rapid breathing; sunken eyes; thirst; unusual tiredness or weakness; wrinkled skin)— disease state may be a contributing factor^{08}





Overdose
For more information on the management of overdose or unintentional ingestion, contact a poison control center (see Poison Control Center Listing)

Note: The maximum amount of darbepoetin alfa that can be safely administered in single or multiple doses has not been determined. Doses over 3 mcg per kg per week for up to 28 weeks have been administered to chronic renal failure (CRF) patients^{01}{08}. Doses up to 8 mcg per kg per week and 15 mcg per kg every 3 weeks of up to 12 to 16 weeks have been administered to cancer patients ^{08}.


Clinical effects of overdose
The following effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:
    
polycythemia ^{01}


Treatment of overdose
For polycythemia—temporarily suspending therapy. In some patients, phlebotomy may be needed^{01}


Monitoring:
Monitor for excessive rise and rate of rise in hemoglobin^{01}



Supportive care:
Patients in whom intentional overdose is confirmed or suspected should be referred for psychiatric consultation.



Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Darbepoetin Alfa (Systemic).
In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Hypersensitivity to darbepoetin alfa or any of the excipients especially albumin
Other medical problems, especially cardiovascular system abnormalities, or hypertension, uncontrolled

Proper use of this medication
» Proper injection technique (if dispensed for home use)

» Safe handling and disposal of needles and syringes

» Proper dosing
Taking as soon as possible; not taking if almost time for next scheduled dose; not doubling doses

Proper storage

Precautions while using this medication
» Importance of keeping medical and dialysis appointments

» Importance of compliance with antihypertensive regimen (medications and diet), if prescribed, and dietary restrictions pertinent to patients with chronic renal failure

» Importance of compliance with iron or other vitamin supplementation


Side/adverse effects
Signs of potential side effects, especially abscess, allergic reaction, angina pectoris, bacteremia, bronchitis, cardiac arrest, cardiac arrhythmias, unspecified chest pain, convulsions (including grand mal and local), congestive heart failure, dyspnea, centralized edema, peripheral edema, fluid overload, access hemorrhage, hypertension, hypotension, access infection, peritonitis, pneumonia, sepsis, vascular access thrombosis, acute myocardial infarction, pulmonary embolism, stroke, and transient ischemic attack


General Dosing Information
Due to individual variability, doses should be titrated to not exceed a target hemoglobin concentration of 12 grams per dL. For many patients, the appropriate maintenance dose will be lower than the starting dose.^{01}

Sufficient time should be allowed to determine a patient's responsiveness to a dosage of darbepoetin alfa before adjusting the dose. Because of the time required for erythropoiesis and the red cell half-life, an interval of 2 to 6 weeks may occur between the time of a dose adjustment and a significant change in hemoglobin. ^{01}

Darbepoetin alfa may be administered either intravenously or subcutaneously for chronic renal failure (CRF) patients.^{01}{08} And, it is administered subcutaneously only for cancer patients receiving concomitant chemotherapy. ^{08}

For treatment of adverse effects
   • For hypertension—Instituting or increasing administration of antihypertensive medications. In some patients, a decrease in darbepoetin alfa dosage or temporary withdrawal of therapy may be needed^{01}.


Parenteral Dosage Forms

Note: Bracketed uses in the Dosage Forms section refers to categories of use and/or indications that are not included in U.S. product labeling.

DARBEPOETIN ALFA INJECTION

Usual Adult Dose
Anemia associated with chronic renal failure
Initial: Intravenous or subcutaneous, 0.45 mcg per kg of body weight once a week. ^{01}
Note:  Due to individual variability, doses should be titrated to not exceed a target hemoglobin concentration of 12 gm per dL. For many patients, the appropriate maintenance dose will be lower than the starting dose. ^{01}
Some patients have been treated successfully with a subcutaneous dose administered once every two weeks. ^{01}


Note: Increases in doses should not be made more than once a month. If the hemoglobin is increasing and approaching 12 gram per dL, the dose should be reduced by approximately 25%. If the hemoglobin continues to increase, doses should be temporarily withheld until the hemoglobin begins to decrease, at which point therapy should be reinitiated at a dose approximately 25% below the previous dose. If the hemoglobin increases by more than 1 gram per dL in a 2-week period, the dose should be decreased by approximately 25%. ^{01}
If the increase in hemoglobin is less than 1 gram per dL over 4 weeks and iron stores are adequate, the dose of darbepoetin alfa may be increased by approximately 25% of the previous dose. Further increases may be made at 4 week intervals until the specified hemoglobin is obtained. ^{01}


Maintenance: Dosage should be adjusted for each patient to achieve and ^{02} maintain a target hemoglobin not to exceed 12 gm per dL. ^{01}

Note: Predialysis patients, in particular, may require a lower maintenance dose. ^{01}

Conversion: Conversion from epoetin alfa to darbepoetin alfa should be estimated on the basis of the weekly epoetin alfa dose at the time of substitution. See Epoetin Conversion Table below. Doses should be titrated to maintain the target hemoglobin. Due to a longer serum half-life, darbepoetin alfa should be administered less frequently than epoetin alfa.

Darbepoetin alfa should be administered once a week if the patient was receiving epoetin alfa 2 to 3 times a week. ^{01}

Darbepoetin alfa should be administered once every two weeks if the patient was receiving epoetin alfa once per week. ^{01}

Note: The route of administration (IV or SC) should be maintained. ^{01}

Previous weekly epoetin alfa dose (Units/week)	Weekly darbepoetin alfa dose (mcg/week)
<2,500	6.25
2,500–4,999	12.5
5,000–10,999	25
11,000–17,999	40
18,000–33,999	60
34,000–89,999	100
³90,000	200

^{01}
Anemia associated with chemotherapy in cancer patients¹
Subcutaneous, 1.5 to ^{08}{12} 2.25 mcg per kg of body weight once a week^{{04}{05}{06}{07}{08}} or [ 3 to 5 mcg per kg body weight once every two weeks]^{1{09}{10}{11}}


Note: The dose should be adjusted for each patient to achieve and maintain a target hemoglobin. If there is less than a 1 gram per dL increase in hemoglobin after 6 weeks of therapy, the dose of darbepoetin alfa should be increased up to 4.5 mcg per kg. If the hemoglobin increases by more than 1 gram per dL in a 2-week period or if the hemoglobin exceeds 12 grams per dL, the dose should be reduced by approximately 25%. If the hemoglobin exceeds 13 grams per dL, doses should be temporarily withheld until the hemoglobin falls to 12 grams per dL. At this point, therapy should be reinitiated at a dose approximately 25% below the previous dose. ^{08}


Usual adult prescribing limits
Target hemoglobin should not exceed 12 gram per dL. ^{01}

Usual Pediatric Dose
Safety and efficacy have not been established.

Usual Geriatric Dose
See Usual adult dose.

Usual geriatric prescribing limits
See Usual adult prescribing limits.

Strength(s) usually available
U.S.—



Albumin Solution


25 mcg per 1 mL (Rx) [Aranesp (albumin human 2.5 mg) (sodium phosphate monobasic monohydrate 2.23 mg) (sodium phosphate dibasic anhydrous 0.53 mg ) (sodium chloride 8.18 mg) ( water for injection, USP)]


40 mcg per 1 mL (Rx) [Aranesp (albumin human 2.5 mg) (sodium phosphate monobasic monohydrate 2.23 mg) (sodium phosphate dibasic anhydrous 0.53 mg ) (sodium chloride 8.18 mg) ( water for injection, USP)]


60 mcg per 1 mL (Rx) [Aranesp ( albumin human 2.5 mg) (sodium phosphate monobasic monohydrate 2.23 mg) (sodium phosphate dibasic anhydrous 0.53 mg) (sodium chloride 8.18 mg) (water for injection, USP)]


100 mcg per 1 mL (Rx) [Aranesp (albumin human 2.5 mg) (sodium phosphate monobasic monohydrate 2.23 mg) (sodium phosphate dibasic anhydrous 0.53 mg ) (sodium chloride 8.18 mg) ( water for injection, USP)]


150 mcg per 0.75 mL (Rx) [Aranesp (albumin human 1.875 mg) (sodium phosphate monobasic monohydrate 1.67 mg) (sodium phosphate dibasic anhydrous 0.40 mg) (sodium chloride 6.14 mg) ( water for injection, USP)]^{08}


200 mcg per 1 mL (Rx) [Aranesp (albumin human 2.5 mg) (sodium phosphate monobasic monohydrate 2.23 mg) (sodium phosphate dibasic anhydrous 0.53 mg ) (sodium chloride 8.18 mg) ( water for injection, USP)]


300 mcg per 1 mL (Rx) [Aranesp (albumin human 2.5 mg) (sodium phosphate monobasic monohydrate 2.23 mg) (sodium phosphate dibasic anhydrous 0.53 mg ) (sodium chloride 8.18 mg) ( water for injection, USP)]^{08}


500 mcg per 1 mL (Rx) [Aranesp (albumin human 2.5 mg) (sodium phosphate monobasic monohydrate 2.23 mg) (sodium phosphate dibasic anhydrous 0.53 mg ) (sodium chloride 8.18 mg) ( water for injection, USP)]^{08}

Canada—



Polysorbate Solution


15 mcg per 1 mL (Rx) [Aranesp (polysorbate 80 0.05 mg) (sodium phosphate monobasic monohydrate 2.12 mg) (sodium phosphate dibasic anhydrous 0.66 mg ) (sodium chloride 8.18 mg) ( water for injection, USP)]^{14}


25 mcg per 1 mL (Rx) [Aranesp (polysorbate 80 0.05 mg) (sodium phosphate monobasic monohydrate 2.12 mg) (sodium phosphate dibasic anhydrous 0.66 mg ) (sodium chloride 8.18 mg) ( water for injection, USP)]^{14}


40 mcg per 1 mL (Rx) [Aranesp (polysorbate 80 0.05 mg) (sodium phosphate monobasic monohydrate 2.12 mg) (sodium phosphate dibasic anhydrous 0.66 mg ) (sodium chloride 8.18 mg) ( water for injection, USP)]^{14}


60 mcg per 1 mL (Rx) [Aranesp ( polysorbate 80 0.05 mg) (sodium phosphate monobasic monohydrate 2.12 mg) (sodium phosphate dibasic anhydrous 0.66 mg) (sodium chloride 8.18 mg) (water for injection, USP)]^{14}


100 mcg per 1 mL (Rx) [Aranesp ( polysorbate 80 0.05 mg) (sodium phosphate monobasic monohydrate 2.12 mg) (sodium phosphate dibasic anhydrous 0.66 mg) (sodium chloride 8.18 mg) (water for injection, USP)]^{14}


200 mcg per 1 mL (Rx) [Aranesp ( polysorbate 80 0.05 mg) (sodium phosphate monobasic monohydrate 2.12 mg) (sodium phosphate dibasic anhydrous 0.66 mg) (sodium chloride 8.18 mg) (water for injection, USP)]^{14}


325 mcg per 1 mL (Rx) [Aranesp (polysorbate 80 0.05 mg) (sodium phosphate monobasic monohydrate 2.12 mg) (sodium phosphate dibasic anhydrous 0.66 mg ) (sodium chloride 8.18 mg) ( water for injection, USP)]^{14}


500 mcg per 1 mL (Rx) [Aranesp (polysorbate 80 0.05 mg) (sodium phosphate monobasic monohydrate 2.12 mg) (sodium phosphate dibasic anhydrous 0.66 mg ) (sodium chloride 8.18 mg) ( water for injection, USP)]^{14}

Packaging and storage:
Store at 2 to 8°C (36 to 46°F). Protect from light. Protect from freezing. ^{01}

Stability:
Do not shake the vial of darbepoetin alfa, recombinant, injection. Shaking may denature the glycoprotein and render it biologically inactive. ^{01}

Do not dilute darbepoetin alfa. ^{01}

Because the single-dose injection contains no preservative, each vial should be used to administer one dose only. Any unused portion of the solution must be discarded. ^{01} Do not pool unused portions. ^{01}

Incompatibilities:
It is recommended that darbepoetin alfa not be administered in conjunction with other drug solutions. ^{01}

Auxiliary labeling:
   • Do not shake.

Developed: 12/10/2001
Revised: 10/03/2002

References

1. Product Information: Aranesp™, darbepoetin alfa. Amgen, Thousand Oaks, CA (PI issued 9/17/2001) reviewed 10/2001.
   

2. Manufacturer comment, 12/01.
   

3. Expert Committee comment, 12/01.
   

4. Reviewers' consensus on ballot of 12/27/01.
   

5. Glapsy J, Singh JJ, Justice G, et al. A dose-finding and safety study of novel erythropoiesis stimulating protein (NESP) for the treatment of anemia in patients receiving multicycle chemotherapy. B J Cancer 2001; 84(S1): 17-23.
   

6. Piker R, Vansteenkiste J, Gateley J, et al. A Phase III, double-blind, placebo-controlled, randomized study of novel erythropoiesis stimulating protein (NESP) in patients undergoing platinum-treatment from lung cancer. Eur J Cancer 2001; 37(S6): 264. Abstract 981
   

7. Heatherington AC, Schuller J, and Mercer AJ. Pharmacokinetics of novel erythropoiesis stimulating protein (NESP) in cancer patients: preliminary report. B J Cancer 2001; 84(S1): 11-6.
   

8. Product Information: Aranesp™, darbepoetin alfa. Amgen, Thousand Oaks, CA (PI issued 7/19/2002) reviewed 08/2002.
   

9. Reviewers' consensus on ballot of 9/21/02.
   

10. Glaspy JA, Jadeja JS, Justice G, et al. Darbepoetin alfa given every 1 or 2 weeks alleviates anemia associated with cancer chemotherapy. B J Cancer 2002;87:268–276.
    

11. Kotasek D, Albertsson M, Mackey J, et al. Randomized, double-blind, placebo-controlled, dose-finding study of darbepoetin alfa administered once every 3 (Q3W) or 4 (Q4W) weeks in patients with solid tumors. American Society of Clinical Oncology, 2002.
    

12. Expert Committee comment, 9/2002.
    

13. Manufacturer comment, 9/2002.
    

14. Product Information: ^PrAranesp™, darbepoetin alfa. Amgen, Mississauga, Ontario (PI issued 8/2/2002) reviewed 10/2002
    

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