About ARANESP® (darbepoetin alfa) | Amgen ESA | HCP

At the center of our story:
sustained efficacy at extended dosing intervals

> 95% of patients on dialysis had their Hb successfully maintained with ARANESP®1,*

Mean change in Hb from baseline to evaluation

Line graph indicating that 97% of patients on dialysis had Hb successfully maintained with ARANESP®

More than

Patients have received
ARANESP® since FDA approval2,†

> 19,000 patients received ARANESP® during nephrology clinical trials3,‡

*Data from a multicenter, randomized, open-label study comparing epoetin, given 1, 2, or 3 times weekly IV or SC, with ARANESP®, at a reduced dose frequency, in dialysis patients (N = 522). Dose adjustments were made as necessary and per study protocol to maintain individual patients’ Hb within a target range of –1.0 to +1.5 g/dL of their baseline Hb and between 9 g/dL and 13 g/dL for up to 52 weeks. The primary endpoint was the change in Hb between baseline and the evaluation period at weeks 25 to 32 of treatment. The mean change in Hb from baseline to the evaluation period was similar in the ARANESP® and epoetin groups, and the difference between the two treatment groups was 0.03 g/dL. This was not a statistically significant or clinically relevant difference. 97% (178/183) of patients’ Hb levels were successfully maintained on ARANESP® QW or less after conversion from epoetin during the evaluation period.1

†In the postmarketing setting from launch through December 31, 2020. The number of patients exposed are based on sales revenue data and include both nephrology and oncology patients.

‡Cumulative estimate based on subjects who received ≥ 1 dose (actual exposure) for completed and ongoing (per protocol randomization) clinical studies from launch through October 2020. There were no additional ongoing or completed studies since October 2018.

FDA = Food and Drug Administration; Hb = hemoglobin; IV = intravenous; SC = subcutaneous; QW = once weekly.

ARANESP® dosing options give you the opportunity to control
administration and provide individualized anemia management4


Graphic indicating how ARANESP® dosing options include 10 mcg, 25 mcg, 40 mcg, 60 mcg, and 100 mcg

ARANESP® is also available in 150, 200, 300, and 500 mcg dose strengths. ARANESP® is available in single-dose vials and prefilled syringes, except the 10, 150, and 500 mcg dose strengths, which are available only as prefilled syringes.

The IV route of administration is recommended for adult patients on hemodialysis.

The molecular structure of ARANESP® provides extended erythropoietic activity that allows for QW and Q2W dosing intervals5,6

Q2W = once every two weeks.




ARANESP® single-dose strengths can be combined4,*


Graphic  showing how 10 mcg, 10 mcg, and 25 mcg coses can be combined to achieve a 45 mcg dose strength

You can more precisely titrate doses and individualize anemia management for patients with CKD on dialysis.

With the 10 mcg dose strength, doses can be precisely titrated within 5 mcg intervals.4,*

ARANESP® Dosing Brochure

Prescribing Information

Dosing at a Glance

*Except the 15 mcg dose.

ARANESP® dosing options give you the opportunity to provide individualized anemia management at extended QW and Q2W dosing intervals4

Icon of a vial and syringe representing multiple dosing options for ARANESP®

ARANESP® SingleJect® Prefilled Syringes

  • Prefilled syringes may reduce potential for dosing errors7
  • UltraSafe® Needle Guard is designed to protect from unintentional needlesticks8
  • QW dosing allows for timely intervention for patients on HD
  • Q2W dosing is a convenient option for patients on PD

Instructions for Use

HD = hemodialysis; PD = peritoneal dialysis.




Dosing information

ARANESP® for anemia due to CKD

  • In controlled trials, patients experienced greater risks for death, serious adverse cardiovascular reactions, and stroke when administered ESAs to target a Hb level of greater than 11 g/dL
  • No trial has identified a Hb target level, ARANESP® dose, or dosing strategy that does not increase these risks
  • Individualize dosing and use the lowest dose of ARANESP® sufficient to reduce the need for RBC transfusions
  • Physicians and patients should weigh the possible benefits of decreasing transfusions against the increased risks of death and other serious cardiovascular adverse events

Considerations

  • Correct or exclude other causes of anemia before initiating ARANESP®
  • Evaluate the iron status in all patients before and during treatment
  • Administer supplemental iron therapy if serum ferritin is < 100 mcg/L or serum transferrin saturation is < 20%
  • The majority of patients with CKD will require supplemental iron during the course of ESA therapy
  • Appropriately control hypertension prior to initiation of and during treatment with ARANESP®
    • Reduce or withhold ARANESP® if blood pressure becomes difficult to control



Initiating and monitoring doses of ARANESP®

INITIATING ARANESP® FOR ADULT PATIENTS WITH CKD ON DIALYSIS

  • Initiate ARANESP® treatment when the Hb level is < 10 g/dL
  • QW recommended starting dose:
    0.45 mcg/kg as an IV or SC injection QW, as appropriate
  • Q2W recommended starting dose:
    0.75 mcg/kg as an IV or SC injection Q2W, as appropriate
  • The IV route of administration is recommended for patients on hemodialysis

INITIATING ARANESP® FOR ADULT PATIENTS WITH CKD NOT ON DIALYSIS

  • Consider initiating ARANESP® treatment only when the Hb level is < 10 g/dL and the following considerations apply:
    • The rate of Hb decline indicates the likelihood of requiring a RBC transfusion, and
    • Reducing the risk of alloimmunization and/or other RBC transfusion-related risks is a goal
  • Q4W recommended starting dose:
    0.45 mcg/kg body weight as an IV or SC injection once at 4 week intervals as appropriate

INITIATING ARANESP® FOR PEDIATRIC PATIENTS (LESS THAN 18 YEARS) WITH CKD

  • Initiate ARANESP® treatment when the Hb level is < 10 g/dL
    On dialysis and not on dialysis:
  • QW recommended starting dose: 0.45 mcg/kg as an IV or SC injection once weekly, as appropriate
    Not on dialysis:
  • QW recommended starting dose: 0.75 mcg/kg as an IV or SC injection once every 2 weeks, as appropriate

MONITORING

Following initiation of therapy and after each dose adjustment, monitor Hb at least weekly until the Hb is stable and sufficient to minimize the need for RBC transfusion.

  • Thereafter, Hb should be monitored at least monthly, provided that Hb levels remain stable

Q4W = once every 4 weeks.




Dose adjustments



esa_icons_1

DOSAGE ADJUSTMENTS

When adjusting therapy, consider Hb rise, rate of decline, ESA responsiveness, and Hb variability.

  • A single Hb excursion may not require a dosing change
  • Do not increase the dose more frequently than once every 4 weeks
  • Decreases in dose can occur more frequently
  • Avoid frequent dose adjustments
esa_icons_2

REDUCE OR INTERRUPT DOSE

If Hb rises rapidly (eg, more than 1 g/dL in any 2-week period), reduce the dose by 25% or more, as needed, to reduce rapid responses.

FOR ADULT PATIENTS WITH CKD:

  • On dialysis: reduce or interrupt dose if the Hb level approaches or exceeds 11 g/dL
  • Not on dialysis: if the Hb level exceeds 10 g/dL, reduce or interrupt the dose of ARANESP®, and use the lowest dose of ARANESP® sufficient to reduce the need for RBC transfusions

FOR PEDIATRIC PATIENTS (LESS THAN 18 YEARS) WITH CKD:

  • If the Hb level approaches or exceeds 12 g/dL, reduce or interrupt the dose of ARANESP®
esa_icons_3

INCREASE DOSE

  • If the Hb has not increased by more than 1 g/dL after 4 weeks of therapy, increase the dose by 25% when appropriate


Patients who do not respond adequately to ARANESP®



  • For patients who do not respond adequately over a 12-week escalation period, increasing the ARANESP® dose further is unlikely to improve response and may increase risks
  • Use the lowest dose that will maintain a Hb level sufficient to reduce the need for RBC transfusions
  • Evaluate other causes of anemia
  • If typical causes of lack or loss of Hb response are excluded, evaluate for pure red cell aplasia (PRCA)
  • Discontinue ARANESP® if responsiveness does not improve

Patients with CKD and an insufficient Hb response to ESA therapy or a rate of Hb rise of > 1 g/dL over 2 weeks may be at an even greater risk for cardiovascular reactions and mortality than other patients.

Conversion to ARANESP®

Converting patients on dialysis from epoetin alfa to QW ARANESP®4

PREVIOUS EPOETIN ALFA DOSE (units/week) QW ARANESP® STARTING DOSE
Adult (mcg/week)
Child(mcg/week)
< 1500 6.25 *
1500 to 2499 6.25 6.25
2500 to 4999 12.5 10
5000 to 10,999 25 20
11,000 to 17,999 40 40
18,000 to 33,999 60 60
34,000 to 89,999 100 100
≥ 90,000 200 200

The dose conversions depicted above do not accurately estimate the
once-monthly dose of ARANESP® in patients with CKD not on dialysis.


Remember to convert your patient’s previous epoetin alfa per-administration
dose to a per-week measurement. Here’s an example of an adult patient4:


PREVIOUS EPOETIN ALFA DOSE ADULT ARANESP® STARTING DOSE
Per administration Per week QW
3000 units/administration x 3 = 9000 units/week 25 mcg
4000 units/administration x 3 = 12,000 units/week 40 mcg

*For pediatric patients receiving a weekly epoetin alfa dose of < 1500 units/week. The available data are insufficient to determine an ARANESP® conversion dose.




Conversion from epoetin alfa

ARANESP® IS ADMINISTERED LESS FREQUENTLY THAN EPOETIN ALFA4

  • Administer ARANESP® once weekly in patients who were receiving epoetin alfa 2 to 3 times weekly
  • Administer ARANESP® once every 2 weeks in patients who were receiving epoetin alfa once weekly
  • Maintain the route of administration (IV or SC injection)
  • The dose conversion in the chart above does not accurately estimate the once-monthly dose of ARANESP®

USE THE FDA-APPROVED ESA CONVERSION TABLE IN THE ARANESP® PI TO CONVERT PATIENTS ON DIALYSIS FROM EPOETIN ALFA TO ARANESP®4

  • Pediatric patients with CKD: ARANESP® safety and efficacy were similar between adults and pediatric patients with CKD when ARANESP® was used for initial treatment of anemia or patients were transitioned from treatment with epoetin alfa to ARANESP®

THERE IS NO SINGLE DCR WHEN CONVERTING FROM EPOETIN ALFA TO ARANESP®4

  • Depending on the dose of epoetin alfa at the time of substitution, the ARANESP®: epoetin alfa DCR may range from 200:1 to 900:1

IV = intravenous; SC = subcutaneous; DCR = dose conversion ratio.

References:

  1. Vanrenterghem Y, Barany P, Mann JFE, et al. Randomized trial of darbepoetin alfa for treatment of renal anemia at a reduced dose frequency compared with rHuEPO in dialysis patients. Kidney Int. 2002;62:2167-2175.
  2. Data on file, Amgen; [ARANESP® Patient Years; 2021].
  3. Data on file, Amgen; [ARANESP® (darbepoetin alfa) Periodic Benefit-Risk Evaluation Report; Jan. 12, 2021].
  4. ARANESP® (darbepoetin alfa) prescribing information, Amgen.
  5. Egrie JC, Browne JK. Development and characterization of novel erythropoiesis stimulating protein (NESP). Br J Cancer. 2001;84(suppl 1):3-10.
  6. Elliott S, Pham E, Macdougall IC. Erythropoietins: a common mechanism of action. Exp Hematol. 2008;26:1573-1584.
  7. Adapa RM, Mani V, Murray LJ, et al. Errors during the preparation of drug infusions: a randomized controlled trial. Br J Anaesth. 2012;109(5):729-734.
  8. UltraSafe® Needle Guards [brochure]. Carlsbad, CA: Safety Syringes, Inc.; 2007.

ARANESP® (darbepoetin alfa) and EPOGEN® (epoetin alfa) Important Safety Information, including Boxed WARNINGS

WARNING: ESAs INCREASE THE RISK OF DEATH, MYOCARDIAL INFARCTION, STROKE, VENOUS THROMBOEMBOLISM, THROMBOSIS OF VASCULAR ACCESS AND TUMOR PROGRESSION OR RECURRENCE

Chronic Kidney Disease:

  • In controlled trials, patients experienced greater risks for death, serious adverse cardiovascular reactions, and stroke when administered erythropoiesis-stimulating agents (ESAs) to target a hemoglobin level of greater than 11 g/dL.
  • No trial has identified a hemoglobin target level, ESA dose, or dosing strategy that does not increase these risks.
  • Use the lowest ARANESP® or EPOGEN® dose sufficient to reduce the need for red blood cell (RBC) transfusions.

Cancer:

  • ESAs shortened overall survival and/or increased the risk of tumor progression or recurrence in clinical studies of patients with breast, non-small cell lung, head and neck, lymphoid, and cervical cancers.
  • To decrease these risks, as well as the risk of serious cardiovascular and thromboembolic reactions, use the lowest dose needed to avoid RBC transfusions.
  • Use ESAs only for anemia from myelosuppressive chemotherapy.
  • ESAs are not indicated for patients receiving myelosuppressive chemotherapy when the anticipated outcome is cure.
  • Discontinue following the completion of a chemotherapy course.

Perisurgery (EPOGEN®):

  • Due to increased risk of Deep Venous Thrombosis (DVT), DVT prophylaxis is recommended.
  • ARANESP® and EPOGEN® are contraindicated in patients with:
    • Uncontrolled hypertension
    • Pure red cell aplasia (PRCA) that begins after treatment with ARANESP®, EPOGEN®, or other erythropoietin protein drugs
    • Serious allergic reactions to ARANESP® or EPOGEN®
  • EPOGEN® from multidose vials contains benzyl alcohol and is contraindicated in neonates, infants, pregnant women, and lactating women.
  • Use caution in patients with coexistent cardiovascular disease and stroke.
  • Patients with CKD and an insufficient hemoglobin response to ESA therapy may be at even greater risk for cardiovascular reactions and mortality than other patients. A rate of hemoglobin rise of > 1 g/dL over 2 weeks may contribute to these risks.
  • In controlled clinical trials, ESAs increased the risk of death in patients undergoing coronary artery bypass graft surgery (CABG) and the risk of deep venous thrombosis (DVT) in patients undergoing orthopedic procedures.
  • Control hypertension prior to initiating and during treatment with ARANESP® or EPOGEN®.
  • ARANESP® and EPOGEN® increase the risk of seizures in patients with CKD. Monitor patients closely for new-onset seizures, premonitory symptoms, or change in seizure frequency.
  • For lack or loss of hemoglobin response to ARANESP® or EPOGEN®, initiate a search for causative factors. If typical causes of lack or loss of hemoglobin response are excluded, evaluate for PRCA.
  • Cases of PRCA and of severe anemia, with or without other cytopenias that arise following the development of neutralizing antibodies to erythropoietin have been reported in patients treated with ARANESP® or EPOGEN®.
    • This has been reported predominantly in patients with CKD receiving ESAs by subcutaneous administration.
    • PRCA has also been reported in patients receiving ESAs for anemia related to hepatitis C treatment (an indication for which ARANESP® and EPOGEN® are not approved).
    • If severe anemia and low reticulocyte count develop during treatment with ARANESP® or EPOGEN®, withhold ARANESP® or EPOGEN® and evaluate patients for neutralizing antibodies to erythropoietin.
    • Permanently discontinue ARANESP® or EPOGEN® in patients who develop PRCA following treatment with ARANESP®, EPOGEN®, or other erythropoietin protein drugs. Do not switch patients to other ESAs.
  • Serious allergic reactions, including anaphylactic reactions, angioedema, bronchospasm, skin rash, and urticaria may occur with ARANESP® or EPOGEN®. Immediately and permanently discontinue ARANESP® or EPOGEN® if a serious allergic reaction occurs.
  • Blistering and skin exfoliation reactions including Erythema multiforme and Stevens-Johnson Syndrome (SJS)/Toxic Epidermal Necrolysis (TEN), have been reported in patients treated with ESAs (including ARANESP® and EPOGEN®) in the postmarketing setting. Discontinue ARANESP® or EPOGEN® therapy immediately if a severe cutaneous reaction, such as SJS/TEN, is suspected.
  • Serious and fatal reactions including “gasping syndrome” can occur in neonates and infants treated with benzyl alcohol-preserved drugs, including EPOGEN® multiple-dose vials. There is a potential for similar risks to fetuses and infants exposed to benzyl alcohol in utero or in breast-fed milk, respectively.
  • Adverse reactions (≥ 10%) in ARANESP® clinical studies in patients with CKD were hypertension, dyspnea, peripheral edema, cough, and procedural hypotension.
  • Adverse reactions (≥ 5%) in EPOGEN® clinical studies in patients with CKD were hypertension, arthralgia, muscle spasm, pyrexia, dizziness, medical device malfunction, vascular occlusion, and upper respiratory tract infection.

Please see ARANESP® full Prescribing Information, including Boxed WARNINGS and Medication Guide.

Please see EPOGEN® full Prescribing Information, including Boxed WARNINGS and Medication Guide.

See More

ARANESP® (darbepoetin alfa) and EPOGEN® (epoetin alfa) Important Safety Information, including Boxed WARNINGS

WARNING: ESAs INCREASE THE RISK OF DEATH, MYOCARDIAL INFARCTION, STROKE, VENOUS THROMBOEMBOLISM, THROMBOSIS OF VASCULAR ACCESS AND TUMOR PROGRESSION OR RECURRENCE

Chronic Kidney Disease:

  • In controlled trials, patients experienced greater risks for death, serious adverse cardiovascular reactions, and stroke when administered erythropoiesis-stimulating agents (ESAs) to target a hemoglobin level of greater than 11 g/dL.
  • No trial has identified a hemoglobin target level, ESA dose, or dosing strategy that does not increase these risks.
  • Use the lowest ARANESP® or EPOGEN® dose sufficient to reduce the need for red blood cell (RBC) transfusions.

Cancer:

  • ESAs shortened overall survival and/or increased the risk of tumor progression or recurrence in clinical studies of patients with breast, non-small cell lung, head and neck, lymphoid, and cervical cancers.
  • To decrease these risks, as well as the risk of serious cardiovascular and thromboembolic reactions, use the lowest dose needed to avoid RBC transfusions.
  • Use ESAs only for anemia from myelosuppressive chemotherapy.
  • ESAs are not indicated for patients receiving myelosuppressive chemotherapy when the anticipated outcome is cure.
  • Discontinue following the completion of a chemotherapy course.

Perisurgery (EPOGEN®):

  • Due to increased risk of Deep Venous Thrombosis (DVT), DVT prophylaxis is recommended.
  • ARANESP® and EPOGEN® are contraindicated in patients with:
    • Uncontrolled hypertension
    • Pure red cell aplasia (PRCA) that begins after treatment with ARANESP®, EPOGEN®, or other erythropoietin protein drugs
    • Serious allergic reactions to ARANESP® or EPOGEN®
  • EPOGEN® from multidose vials contains benzyl alcohol and is contraindicated in neonates, infants, pregnant women, and lactating women.
  • Use caution in patients with coexistent cardiovascular disease and stroke.
  • Patients with CKD and an insufficient hemoglobin response to ESA therapy may be at even greater risk for cardiovascular reactions and mortality than other patients. A rate of hemoglobin rise of > 1 g/dL over 2 weeks may contribute to these risks.
  • In controlled clinical trials, ESAs increased the risk of death in patients undergoing coronary artery bypass graft surgery (CABG) and the risk of deep venous thrombosis (DVT) in patients undergoing orthopedic procedures.
  • Control hypertension prior to initiating and during treatment with ARANESP® or EPOGEN®.
  • ARANESP® and EPOGEN® increase the risk of seizures in patients with CKD. Monitor patients closely for new-onset seizures, premonitory symptoms, or change in seizure frequency.
  • For lack or loss of hemoglobin response to ARANESP® or EPOGEN®, initiate a search for causative factors. If typical causes of lack or loss of hemoglobin response are excluded, evaluate for PRCA.
  • Cases of PRCA and of severe anemia, with or without other cytopenias that arise following the development of neutralizing antibodies to erythropoietin have been reported in patients treated with ARANESP® or EPOGEN®.
    • This has been reported predominantly in patients with CKD receiving ESAs by subcutaneous administration.
    • PRCA has also been reported in patients receiving ESAs for anemia related to hepatitis C treatment (an indication for which ARANESP® and EPOGEN® are not approved).
    • If severe anemia and low reticulocyte count develop during treatment with ARANESP® or EPOGEN®, withhold ARANESP® or EPOGEN® and evaluate patients for neutralizing antibodies to erythropoietin.
    • Permanently discontinue ARANESP® or EPOGEN® in patients who develop PRCA following treatment with ARANESP®, EPOGEN®, or other erythropoietin protein drugs. Do not switch patients to other ESAs.
  • Serious allergic reactions, including anaphylactic reactions, angioedema, bronchospasm, skin rash, and urticaria may occur with ARANESP® or EPOGEN®. Immediately and permanently discontinue ARANESP® or EPOGEN® if a serious allergic reaction occurs.
  • Blistering and skin exfoliation reactions including Erythema multiforme and Stevens-Johnson Syndrome (SJS)/Toxic Epidermal Necrolysis (TEN), have been reported in patients treated with ESAs (including ARANESP® and EPOGEN®) in the postmarketing setting. Discontinue ARANESP® or EPOGEN® therapy immediately if a severe cutaneous reaction, such as SJS/TEN, is suspected.
  • Serious and fatal reactions including “gasping syndrome” can occur in neonates and infants treated with benzyl alcohol-preserved drugs, including EPOGEN® multiple-dose vials. There is a potential for similar risks to fetuses and infants exposed to benzyl alcohol in utero or in breast-fed milk, respectively.
  • Adverse reactions (≥ 10%) in ARANESP® clinical studies in patients with CKD were hypertension, dyspnea, peripheral edema, cough, and procedural hypotension.
  • Adverse reactions (≥ 5%) in EPOGEN® clinical studies in patients with CKD were hypertension, arthralgia, muscle spasm, pyrexia, dizziness, medical device malfunction, vascular occlusion, and upper respiratory tract infection.

Please see ARANESP® full Prescribing Information, including Boxed WARNINGS and Medication Guide.

Please see EPOGEN® full Prescribing Information, including Boxed WARNINGS and Medication Guide.