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.
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No trial has identified a hemoglobin target level, ESA dose, or dosing strategy that does not
increase these risks.
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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.
