Indication and Limitations of Use

EPOGEN® is indicated for the treatment of anemia due to chronic kidney disease (CKD) in patients on dialysis to decrease the need for red blood cell (RBC) transfusion.
EPOGEN® has not been shown to improve quality of life, fatigue, or patient well-being.
EPOGEN® is not indicated for use as a substitute for RBC transfusions in patients who require immediate correction of anemia.

The flexibility of EPOGEN® TIW (three times weekly) dosing allows for timely intervention to help address Hb changes1,2

  • 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 hemoglobin target level, ESA dose, or dosing strategy that does not increase these risks.
  • Individualize dosing and use the lowest dose of EPOGEN® 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 reactions.

Considerations

  • Correct or exclude other causes of anemia before initiating EPOGEN®.
  • Evaluate the iron status of 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.
  • In pregnant women, lactating women, neonates, and infants use only single-dose vials (the benzyl alcohol-free formulation). Do not mix EPOGEN® with bacteriostatic saline (which contains benzyl alcohol) when administering to these patients.
  • Appropriately control hypertension prior to initiation of and during treatment with EPOGEN®.
  • Reduce or withhold EPOGEN® if blood pressure becomes difficult to control.

TO INITIATE EPOGEN® FOR ADULT PATIENTS

Initiate EPOGEN® treatment when the Hb level is < 10 g/dL.
The recommended starting dose for adult patients is 50 to 100 Units/kg 3 times weekly intravenously or subcutaneously. The intravenous route of administration is recommended for patients on hemodialysis.

TO INITIATE EPOGEN® FOR PEDIATRIC PATIENTS (ages 1 month or older)

Initiate EPOGEN® treatment only when the Hb level is < 10 g/dL.
The recommended starting dose for pediatric patients is 50 Units/kg 3 times weekly intravenously or subcutaneously. The intravenous route of administration is recommended for patients on hemodialysis.

MONITOR AND ASSESS Hb REGULARLY

Following initiation of therapy and after each dose adjustment, monitor Hb at least weekly until the Hb level 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.

DOSAGE ADJUSTMENT

When adjusting therapy, consider Hb rate of 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.

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:
  • Reduce or interrupt dose if the Hb level approaches or exceeds 11 g/dL.
FOR PEDIATRIC PATIENTS (ages 1 month or older):
  • Reduce or interrupt dose if the Hb level approaches or exceeds 12 g/dL.

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.

IMPORTANT SAFETY INFORMATION

  • 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 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 EPOGEN® is not approved).
    • If severe anemia and low reticulocyte count develop during treatment with EPOGEN®, withhold EPOGEN® and evaluate patients for neutralizing antibodies to erythropoietin.
    • Permanently discontinue EPOGEN® in patients who develop PRCA following treatment with EPOGEN® or other erythropoietin protein drugs. Do not switch patients to other ESAs.


Scroll down for additional Important Safety Information

Patients who do not respond adequately to EPOGEN®

  • For patients who do not respond adequately over a 12-week escalation period, increasing the EPOGEN® 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 EPOGEN® if responsiveness dose 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 even greater risk for cardiovascular reactions and mortality than other patients.

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 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:
  • Due to increased risk of Deep Venous Thrombosis (DVT), DVT prophylaxis is recommended.
  • EPOGEN® is contraindicated in patients with:
    • Uncontrolled hypertension
    • Pure red cell aplasia (PRCA) that begins after treatment with EPOGEN® or other erythropoietin protein drugs
    • Serious allergic reactions to 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 EPOGEN®.
  • EPOGEN® increases 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 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 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 EPOGEN® is not approved).
    • If severe anemia and low reticulocyte count develop during treatment with EPOGEN®, withhold EPOGEN® and evaluate patients for neutralizing antibodies to erythropoietin.
    • Permanently discontinue EPOGEN® in patients who develop PRCA following treatment with 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 EPOGEN®. Immediately and permanently discontinue 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 EPOGEN®) in the postmarketing setting. Discontinue 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 (≥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.

Indication and Limitations of Use

EPOGEN® is indicated for the treatment of anemia due to chronic kidney disease (CKD) in patients on dialysis to decrease the need for red blood cell (RBC) transfusion.
EPOGEN® has not been shown to improve quality of life, fatigue, or patient well-being.
EPOGEN® is not indicated for use as a substitute for RBC transfusions in patients who require immediate correction of anemia.

 

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