Utilization Review Policy
Subject:
epoetin alfa injection (Procrit®, Epogen®)
Date revised: 12/2/2009
Description
Epoetin alfa is an erythroid stimulating agent (ESA) that is approved by the Food and Drug
Administration (FDA) for the following indications.1-2
Treatment of anemia of chronic renal failure (CRF).
Treatment of anemia in zidovudine-treated Human Immunodeficiency Virus (HIV)infected patients.
Treatment of anemia in cancer patients on chemotherapy.
Reduction of allogeneic blood transfusion in surgery patients.
Epoetin alfa is given intravenously (IV) or subcutaneously (SC). Epoetin alfa is available as
Epogen and Procrit which are supplied as a solution in single-dose and multidose vials, both with
preservatives and preservative-free. The products are available in various strengths.
Indications, Medically Necessary
1. Anemia in CRF: Indicated for the treatment of anemia associated with CRF in patients
(adults and children) who meet all of the following criteria.

Hb level is ≤ 10.0 g/dL for therapy initiation. Note: For patients currently receiving
darbepoetin alfa (Aranesp) or epoetin alfa, hemoglobin (Hb) should be ≤ 12.0 g/dL.
Dosing in CRF: The starting dose for correction of anemia is 50 to 100 Units/kg three times
weekly (TIW) IV or SC for adult patients.1-2 For pediatric CRF patients on dialysis the dose
is 50 Units/kg TIW SC or IV. For patients on hemodialysis, the IV route is recommended.
The dose is individualized to achieve and maintain Hb within the range of 10.0 to 12.0 g/dL.
Refer to the package insert regarding titration of epoetin alfa.
Initial approval/extended approval in CRF: For patients initiating therapy, approval is for
3 months. Patients are evaluated for response after 3 months. Approve for an additional six
months if a Hb response is achieved and Hb ≤ 12.0 g/dL. For patients not responding,
despite dose titrations during the first 3 months, discontinue epoetin alfa and evaluate and
treat for other causes of anemia. In some patients, Hb may not increase but stay the same and
not decrease further. This may be interpreted as a response. For patients on maintenance
therapy, approve for 6 months if the patient continues to respond and if Hb ≤ 12.0 g/dL.
Afterwards, continue to approve epoetin alfa at 6 month intervals if the patient is responding
and Hb ≤ 12.0 g/dL.
12/2/2009
1
epoetin alfa injection (Procrit, Epogen)
Duration of therapy in CRF: may be indefinite as long as the patient has CRF.
Labs/Diagnostics required: Monitor Hb regularly. Iron status must be evaluated (for
example, serum iron, total iron binding capacity, serum ferritin, per cent transferrin saturation
[TSAT], bone marrow biopsy) before initiating therapy and as needed during treatment.
Waste management: Single-dose vials and syringes are available in many different
strengths. The dose should be calculated and the number of vials/syringes needed assessed.
Refer
to
the
package
insert
for
more
information.
http://www.epogen.com/professional/resources/prescribing_information/pi.jsp
http://www.procrit.com/
Exclusions: CRF. Also see below.
 Use beyond 3 months in the absence of response in CRF patients.
2. Anemia due to cancer chemotherapy: Indicated for anemia in non-myeloid
malignancies due to chemotherapy (that will be administered for at least 2 months) in
patients (adults and children) who meet all of the following criteria.

Hb level is ≤ 10.0 g/dL for therapy initiation, and Note: For patients currently receiving
darbepoetin alfa (Aranesp) or epoetin alfa, Hb should be ≤ 12.0 g/dL.

Patient is currently receiving myelosuppressive chemotherapy, and (Note: myelosuppressive
chemotherapy regimens associated with an increased risk of anemia are listed in the National
Comprehensive Cancer Network [NCCN] guidelines.3 These references may not be a
complete list, as new regimens are being developed).

Epoetin alfa is being prescribed by a hematologist or oncologist, and

Patient has a metastatic, non-myeloid malignancy and the anticipated outcome is not cure,
and

Absolute iron deficiency has been excluded (serum ferritin < 30 ng/dL and transferrin
saturation < 15%).
Dosing in anemia due to cancer chemotherapy: Various doses have been used. Initial and
some maximum dosing are listed.
Adults
 epoetin alfa 150 Units/kg TIW SC (increase epoetin alfa up to 300 Units/kg TIW SC).1-3
 epoetin alfa 40,000 Units once every week SC (increase dose of epoetin alfa to 60,000
units every week by SC injection).1-3
 epoetin alfa 80,000 Units every 2 weeks SC.1-3
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epoetin alfa injection (Procrit, Epogen)
 epoetin alfa 120,000 Units every 3 weeks SC.1-3
Pediatric patients
 epoetin alfa 600 Units/kg IV weekly.1-3
The dose should be adjusted for each patient to maintain the lowest Hb level sufficient to
avoid red blood cell transfusions. Discontinue epoetin alfa if after 8 weeks of therapy there
is no response as measured by Hb levels or if transfusions are still required.
Initial approval/extended approval in anemia due to cancer chemotherapy: Approve for
an initial 2 months to monitor for Hb values and check the appropriate doses. Epoetin alfa
should be discontinued after 8 weeks of therapy if there is no response as measured by Hb
levels or if transfusions are still required; evaluate and treat for other causes of anemia.1 In
some patients, Hb may not increase but stay the same and not decrease further. This may be
interpreted as a response. If the patient has a response after 8 weeks (2 months), approve at
4-month intervals if the patient is still receiving chemotherapy during this time frame (plus
within six weeks after chemotherapy discontinuation). At each 4-month interval, assure that
Hb values are ≤ 12.0 g/dL at all times, otherwise therapy should be discontinued or withheld.
Discontinue epoetin alfa when chemotherapy treatment is complete and anemia has resolved,
usually within 6 weeks.
Labs/Diagnostics required: After dose adjustment, the Hb should be determined weekly
for at least 4 weeks until it has been determined that the Hb has stabilized in response to the
dose change. The Hb should be monitored at regular intervals. Iron status must be evaluated
(for example, serum iron, total iron binding capacity, serum ferritin, per cent transferrin
saturation [TSAT], bone marrow biopsy) before initiating therapy and as needed during
treatment. Hb should always be ≤ 12.0 g/dL for continuation of therapy.
Waste management: Single-dose vials and multidose vials are available in many different
strengths. The dose should be calculated and the number of vials needed assessed. Refer to
the
package
insert
for
more
information.
http://www.epogen.com/professional/resources/prescribing_information/pi.jsp
http://www.procrit.com/
Exclusions: anemia due to cancer chemotherapy. See also below.
 Use beyond 8 weeks in the absence of response or in those receiving transfusions.
 Continued use when chemotherapy treatment is complete and anemia has resolved
(usually within 6 weeks of the last dose of chemotherapy).
 Absolute iron deficiency (serum ferritin < 30 ng/dL and transferrin saturation < 15%).
 Use is not indicated for patients when the anticipated outcome is cure.
3. Treatment of anemia in zidovudine-treated HIV-infected patients: Indicated for the
treatment of anemia related to therapy with zidovudine in HIV-infected patients (adults and
children) who meet all of the following criteria.
12/2/2009
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epoetin alfa injection (Procrit, Epogen)



Hb level is ≤ 10.0 g/dL for therapy initiation, and Note: For patients currently receiving
darbepoetin alfa (Aranesp) or epoetin alfa, Hb should be ≤ 12.0 g/dL.
Baseline endogenous serum erythropoietin level is ≤ 500 mUnits/mL, and
Adults must be receiving a dose of zidovudine ≤ 4200 mg/week. For children, no specific
zidovudine dosage is specified.
Dosing for anemia in zidovudine-treated HIV-infected patients:
 For adults: initiate at 100 Units/kg IV or SC TIW for 8 weeks and increase up to 300
Units/kg TIW.
 For pediatric patients: 50 to 400 Units/kg SC or IV two to three times per week.
The dosage should be adjusted and titrated to achieve the Hb goals desired, but Hb must not
exceed 12.0 g/dL.
Initial approval/extended approval for anemia in zidovudine-treated HIV-infected
patients: Initial approval is for 3 months. Patients are evaluated for Hb response after 3
months. If no response is achieved, discontinue therapy and evaluate for other causes of
anemia. If the patient achieves a Hb response, and Hb is ≤ 12.0 g/dL, approve epoetin alfa
therapy at 6-month intervals. Discontinue epoetin alfa when the patient stops zidovudine
therapy.
Labs/Diagnostics required: Iron status must be evaluated prior to therapy and as needed
during treatment (for example, serum iron, total iron binding capacity, serum ferritin, per
cent transferrin saturation [TSAT], bone marrow biopsy). Hb should be monitored for
response and not to exceed 12.0 g/dL.
Waste management: Single-dose vials and multidose vials are available in many different
strengths. The dose should be calculated and the number of vials needed assessed. Refer to
the
package
insert
for
more
information.
http://www.epogen.com/professional/resources/prescribing_information/pi.jsp
http://www.procrit.com/
Exclusions: anemia in zidovudine-treated HIV-infected patients. See also below.
 Use when zidovudine therapy is discontinued.
 Baseline serum erythropoietin levels > 500 mUnits/mL.
 Pre-treatment Hb > 10.0 g/dL.
 Continued use after non-response to doses of epoetin alfa > 300 units/kg TIW for
adults.
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epoetin alfa injection (Procrit, Epogen)
4. Reduction of allogeneic blood transfusion in surgery patients: Indicated for the
treatment of anemic adult patients prior to surgery who are at high risk for perioperative
blood loss who meet all of the following criteria.

Hb level is ≤ 13.0 g/dL for therapy initiation, and

Patient must be undergoing elective, noncardiac, nonvascular surgery, and

Patient is not willing or able to donate autologous blood, and

Patients are receiving adequate iron supplementation.
Dosing in adults undergoing surgery (to reduce allogeneic blood transfusions):
 epoetin alfa 300 Units/kg/day SC for 10 days before surgery, on the day of surgery and
for 4 days after surgery.
 epoetin alfa 600 Units/kg SC in once weekly doses (21, 14 and 7 days before surgery)
plus a fourth dose on the day of surgery.
Initial approval/extended approval in patients undergoing surgery (to reduce allogeneic
blood transfusions): Approve for either 11 doses (daily for 10 days before surgery and the
day of surgery if the dose is 300 Units/kg/day) or for 4 doses (3 weekly doses and 1 dose the
day of surgery if the dose is 600 Units/kg once weekly).
Labs/Diagnostics required: Iron status must be evaluated (for example, serum iron, total
iron binding capacity, serum ferritin, per cent transferrin saturation [TSAT], bone marrow
biopsy) before initiating therapy.
Waste management: Single-dose vials and multidose vials are available in many different
strengths. The dose should be calculated and the number of vials needed assessed. Refer to
the
package
insert
for
more
information.
http://www.epogen.com/professional/resources/prescribing_information/pi.jsp
http://www.procrit.com/
Exclusions: patients undergoing surgery (to reduce allogeneic blood transfusions). See
also below.
 Continued use for more than 14 days and 21 days.
 Pre-treatment Hb ≥ 13.0 g/dL
 Patient is willing or able to donate autologous blood.
 Patients undergoing coronary artery bypass graft surgery.
 Pediatric patients (aged < 18 years).
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epoetin alfa injection (Procrit, Epogen)
5. Anemia in myelodysplastic syndromes (MDS): Indicated for the treatment of anemia
associated with MDS in adults who meet all of the following criteria. [NOT FDA
APPROVED INDICATION]

Hb level is ≤ 12.0 g/dL for therapy initiation, and

Serum erythropoietin level is ≤ 500 mU/mL, and

Epoetin alfa is prescribed by a hematologist or an oncologist.
Dosing in MDS: The dose of epoetin alfa is 40,000-60,000 Units 1-3 times weekly SC.
Initial approval/extended approval in MDS: For patients initiating therapy, approval is for
4 months. Patients are evaluated for an erythroid response after 4 months. Approve for an
additional six months if an erythroid response is achieved (increase in Hb or a decrease in
transfusions) and Hb ≤ 12.0 g/dL. For patients not responding, despite dose titrations and/or
concomitant use of granulocyte colony stimulating factor (G-CSF) during the first 4 months,
discontinue epoetin alfa and evaluate and treat for other causes of anemia. For patients on
maintenance therapy, approve for 4 months if the patient continues to have an erythroid
response and if Hb ≤ 12.0 g/dL. Afterwards, continue to approve epoetin alfa at 4-month
intervals if the patient is responding and Hb ≤ 12.0 g/dL.
Duration of therapy in MDS: may be indefinite as long as patient has MDS.
Labs/Diagnostics required: Evaluate for erythroid response (Hb increase and/or a decrease
in transfusions) regularly. Iron status must be evaluated (for example, serum iron, total iron
binding capacity, serum ferritin, per cent transferrin saturation [TSAT], bone marrow biopsy)
before initiating therapy and as needed during treatment.
Waste management: Single-dose vials and multidose vials are available in many different
strengths. The dose should be calculated and the number of vials/syringes needed assessed.
Refer
to
the
package
insert
for
more
information.
http://www.epogen.com/professional/resources/prescribing_information/pi.jsp
http://www.procrit.com/
Exclusions: MDS. See also below.
 Serum erythropoietin level > 500 mU/mL.
 Use beyond 4 months in the absence of an erythroid response in MDS patients.
 Use in children (aged < 18 years).
6. Treatment of anemia associated with chronic hepatitis C treatment (e.g.,
peginterferon/interferon [PEG-Intron®, Pegasys®] plus ribavirin therapy): Indicated for
12/2/2009
6
epoetin alfa injection (Procrit, Epogen)
the treatment of anemia associated with chronic hepatitis C treatment in adults who meet all
of the following criteria. [NOT FDA-APPROVED INDICATION]

Hb levels ≤ 10.0 g/dL for therapy initiation, and Note: for patients currently receiving
darbepoetin alfa (Aranesp) or epoetin alfa, Hb should be ≤ 12.0 g/dL.

Patient is receiving therapy for the treatment of chronic hepatitis C (e.g., peginterferon
alfa/interferon alfa therapy plus ribavirin), and

Epoetin alfa is prescribed by a hepatologist, gastroenterologist, or infectious disease
physician who specializes in the management of hepatitis C.
Dosing in anemia due to chronic hepatitis C treatment: The initial and maximum dose is
epoetin alfa 40,000 Units SC once weekly (titrate downward as needed to maintain Hb ≤ 12.0
g/dL) in adults.5-6
Initial approval/extended approval in anemia due to chronic hepatitis C treatment: For
patients initiating therapy, approval is for 6 months if the duration of the treatment of
hepatitis C (peginterferon alfa/interferon alfa plus ribavirin) is also this long (if not, only
approve for the duration of the hepatitis C therapy). Patients are evaluated for a Hb response
after 6 months. Approve for an additional six months if an increase in Hb is achieved and Hb
≤ 12.0 g/dL. For patients not responding, despite dose titrations, discontinue epoetin alfa;
evaluate and treat for other causes of anemia. For patients on maintenance therapy with
epoetin alfa, approve for 6 months if the patient continues to have a Hb response and if Hb ≤
12.0 g/dL. For all patients, therapy with epoetin alfa should stop when the treatment with
ribavirin for hepatitis C is discontinued (generally one year total).
Duration of therapy in anemia due to chronic hepatitis C treatment: Patients may
receive epoetin alfa therapy only if the patient is also receiving therapy with ribavirin for
hepatitis C, which is usually approximately one year for most patients.
Labs/Diagnostics required: Monitor Hb regularly and evaluate for response. Iron status
must be evaluated (for example, serum iron, total iron binding capacity, serum ferritin, per
cent transferrin saturation [TSAT], bone marrow biopsy) before initiating therapy and as
needed during treatment.
Waste management: Single-dose and multidose vials are available in many different
strengths. The dose should be calculated and the number of vials/syringes needed assessed.
Refer
to
the
package
insert
for
more
information.
http://www.epogen.com/professional/resources/prescribing_information/pi.jsp
http://www.procrit.com/
Exclusions: anemia due to chronic hepatitis C treatment. See below.
12/2/2009
7
epoetin alfa injection (Procrit, Epogen)



Anemia in a patient with hepatitis C who is not receiving ribavirin.
Use beyond 6 months in the absence of a Hb response.
Use in children (aged < 18 years).
Exclusions for all:
 Continued use when Hb exceeds 12.0 g/dL.
 Treatment of cancer-related anemia in those not receiving myelosuppressive chemotherapy.
 Epoetin alfa is not indicated for use in patients receiving hormonal agents, therapeutic
biologic products, or radiotherapy unless receiving concomitant myelosuppressive
chemotherapy.
 Treatment of anemia in patients with acute myelogenous leukemia or chronic myelogenous
leukemias (examples of myeloid cancers).
 Use in patients with underlying hematologic diseases (e.g., hemolytic anemia, sickle cell
anemia, thalassemia, porphyria).
 To treat anemia in patients with other risk factors such as iron deficiency, folate deficiency or
B12 deficiency, hemolysis, gastrointestinal bleeding, active or occult bleeding.
 Patients with uncontrolled hypertension.
 Anemia in patients due to acute blood loss.
 Non-anemic patients (Hb > 13.0 g/dL) prior to surgery.
ABBREVIATIONS
CRF = chronic renal failure
FDA = Food and Drug Administration
ESA = erythroid stimulating agent
G-CSF = granulocyte colony stimulating factor
Hb = hemoglobin
HIV = Human Immunodeficiency Virus
IV = intravenous
MDS = myelodysplastic syndrome
mL = milliliter
NCCN = National Comprehensive Cancer Network
SC = subcutaneous
TIW = three times weekly
TSAT = percent transferrin saturation
< less than
≤ less than or equal to
> greater than
12/2/2009
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epoetin alfa injection (Procrit, Epogen)
≥ greater than or equal to
REFERENCES
Procrit for injection [package insert]. Raritan, NJ: Ortho Biotech, Inc; April 2009.
Epogen for injection [package insert]. Thousand Oaks, CA: Amgen, Inc; April 2009.
National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology. Cancer and chemotherapy-related
anemia. Version 2.2010. Accessed on 10/13/2009 at http://www.nccn.org/professionals/physician_gls/PDF/anemia.pdf
4. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology. Myelodysplastic syndromes. Version
2.2010. Accessed on 10/13/2009 at http://www.nccn.org/professionals/physician_gls/PDF/mds.pdf
5. Dieterich DT, Wasserman R, Brau N, et al. Once-weekly epoetin alfa improves anemia and facilitates maintenance of
ribavirin dosing in hepatitis C virus-infected patients receiving ribavirin plus interferon alfa. Am J Gastroenterol.
2003;98(11):2491-2499.
6. Afdahl NH, Dieterich DT, Pockros PJ, et al. Epoetin alfa maintains ribavirin dose in HCV-infected patients: a prospective,
double-blind, randomized controlled study. Gastroenterology. 2004;126(5):1302-1311.
Anemia in chronic kidney disease

Singh AK, Szczech L, Tang KL, et al, for the CHOIR Investigators. Correction of anemia with epoetin alfa in chronic
kidney disease. N Engl J Med. 2006;355:2085-2098.

Besarab A, Bolton WK, Browne JK, et al. The effects of normal as compared with low hematocrit values in patients with
cardiac disease who are receiving hemodialysis and epoetin. N Engl J Med. 1998;339:584-590.

KDOQI; National Kidney Foundation. Clinical practice guidelines and clinical practice recommendations for anemia in
chronic kidney disease in adults. Am J Kidney Dis. 2006;47(5 Suppl 3):S16-S85. Accessed on 12/2/2009 at
http://www.kidney.org/professionals/kdoqi/guidelines_anemia/index.htm

KDOQI; National Kidney Foundation. KDOQI clinical practice guideline and clinical practice recommendations for anemia
in chronic kidney disease. 2007 update of the hemoglobin target. Am J Kidney Dis. 2007;50(3):476-530.

KDOQI; National Kidney Foundation. III. Clinical practice recommendations for anemia in chronic kidney disease in
children. Am J Kidney Dis. 2006;47(5 Suppl 3):S86-S108.
Anemia in cancer chemotherapy

Leyland-Jones B, Semiglazov V, Pawlicki M, et al. Maintaining normal hemoglobin levels with epoetin alfa in mainly
nonanemic patients with metastatic breast cancer receiving first-line chemotherapy: a survival study. J Clin Oncol.
2005;23(25):5960-5972.

Bohlius J, Wilson J, Seidenfeld J, et al. Recombinant human erythropoietins and cancer patients; updated meta-analysis of
57 studies including 9353 patients. J Natl Cancer Inst. 2006;98:708-714.

Wright JR, Ung YC, Julian JA, et al. Randomized, double-blind, placebo-controlled trial of erythropoietin in non-small-cell
lung cancer with disease-related anemia. J Clin Oncol. 2007;25:1027-1032.

Smith RE, Aapro MS, Ludwig H, et al. Darbepoetin alfa for the treatment of anemia in patients with active cancer not
receiving chemotherapy or radiotherapy: results of a phase III, multicenter, randomized, double-blind, placebo-controlled
study. J Clin Oncol. 2008;26(7):1040-1050.

Thomas G, Ali S, Hoebers FJP, et al. Phase III trial to evaluate the efficacy of maintaining hemoglobin levels above 120
g/dL with erythropoietin vs. above 100 g/dL without erythropoietin in anemic patients receiving concurrent radiation and
cisplatin for cervical cancer: a gynecologic oncology group study. Gynecol Oncol. 2008;108(2):317-325.

Henke M, Laszig R, Rube C, et al. Erythropoietin to treat head and neck cancer patients with anaemia undergoing
radiotherapy: randomized, double-blind, placebo-controlled trial. Lancet. 2003;362:1255-1260.

Bohlius J, Schmidlin K, Brillant C, et al. Recombinant human erythropoiesis-stimulating agents and mortality in patients
with cancer: a meta-analysis of randomized trials. Lancet. 2009;373:1532-1542.

Tonelli M, Hemmelgarn B, Reiman T, et al. Benefits and harms of erythropoiesis-stimulating agents for anemia related to
cancer: a meta-analysis. CMAJ. 2009;180(11):E62-E71.

Rizzo JD, Somerfield MR, Hagerty KL, et al. Use of epoetin and darbepoetin in patients with cancer: 2007 American
Society of Clinical Oncology/American Society of Hematology clinical practice guideline update. J Clin Oncol.
2008;26(1):132-149.
Anemia in AIDS association with zidovudine

Fischl M, Galpin JE, Levine JD, et al. Recombinant human erythropoietin for patients with AIDS treated with zidovudine.
N Engl J Med. 1990;322:1488-1493.
Use in surgery
1.
2.
3.
12/2/2009
9
epoetin alfa injection (Procrit, Epogen)

de Andrade JR, Jove M. Baseline hemoglobin as a predictor of risk of transfusion and response to epoetin alpha in
orthopedic surgery patients. Am J Orthoped. 1996;25(8):533-542.

Goldberg MA, McCutchen JW. A safety and efficacy comparison study of two dosing regimens of epoetin alpha in patients
undergoing major orthopedic surgery. Am J Orthoped. 1996;25(8):544-552.

D’Ambra MN, Gray RJ, Hillman R, et al. Effect of recombinant human erythropoietin on transfusion risk in coronary
bypass patients. Ann Thorac Surg. 1997;64(6):1686-1693.

Faris PM, Ritter MA, Abels RI. The effects of recombinant human erythropoietin on perioperative transfusion requirements
in patients having a major orthopaedic operation. The American Erythropoietin Study Group. J Bone Joint Surg.
1996;78(1):62-72.
Myelodysplastic syndrome [NOT FDA-APPROVED]

Stone RM. How I treat patients with myelodysplastic syndromes. Blood. 2009;113:6296-6303.

Ross DS, Allen IE, Probst CA, et al. Efficacy and safety of erythropoiesis-stimulating proteins in myelodysplastic
syndrome: a systematic review and meta-analysis. The Oncologist. 2007;12:1264-1273.

Patton JF, Sullivan T, Mun Y, et al. A retrospective cohort study to assess the impact of therapeutic substitution of
darbepoetin alfa for epoetin alfa in anemic patients with myelodysplastic syndrome. J Support Oncol. 2005;3:419-426.

Italian Cooperative Study Group for rHuEpo in myelodysplastic syndromes. A randomized double-blind placebo-controlled
study with subcutaneous recombinant human erythropoietin in patients with low-risk myelodysplastic syndromes. Br J
Haematol. 1998;103(4):1070-1074.

Thompson JA, Gilliland G, Prchal TJ, et al.
Effect of recombinant human erythropoietin combined with
granulocyte/macrophage colony-stimulating factor in the treatment of patients with myelodysplastic syndrome. Blood.
2000;95:1175-1179.

Stasi R, Pagano A, Terzoli E, Amadori S. Recombinant human granulocyte-macrophage colony-stimulating factor plus
erythropoietin for the treatment of cytopenias in patients with myelodysplastic syndromes.
Br J Haematol.
1999;105(1):141-148.

Hellstrom-Lindberg E, Gulbrandsen N, Lindberg G, et al. A validated decision model for treating the anemia of
myelodysplastic syndromes with erythropoietin + granulocyte colony-stimulating factor: significant effects on quality of
life. Br J Haematol. 2003;120(6):1037-1046.

Terpos E, Mougiou A, Kouraklis A, et al. Prolonged administration of erythropoietin increases erythroid response rate in
myelodysplastic syndromes: a phase II trial in 281 patients. Br J Haematol. 2002;118:174-180.

Mantovani L, Lentini G, Hentschel B, et al. Treatment of anemia in myelodysplastic syndromes with prolonged
administration of recombinant human granulocyte colony-stimulating factor and erythropoietin. Br J Haematol.
2000;109(2):367-375.

Stasi R, Brunetti M, Terzoli E, et al. Once-weekly dosing of recombinant human erythropoietin alpha in patients with
myelodysplastic syndromes unresponsive to conventional dosing. Ann Oncol. 2004;15(11):1684-1690.

Spiriti MA, Latagliata R, Niscola P, et al. Impact of a new dosing regimen of epoetin alfa on quality of life and anemia in
patients with low-risk myelodysplastic syndrome. Ann Hematol. 2005;84(3):167-176.
Anemia in chronic hepatitis C [NOT FDA-APPROVED]

Ghany MG, Strader DB, Thomas DL, Seeff LB. Diagnosis, management and treatment of hepatitis C: an update.
Hepatology. 2009;49(4):2335-1374.

McHutchison JG, Lawitz EJ, Schiffman ML, et al, for the IDEAL study team. Peginterferon alfa-2b or alfa-2a with
ribavirin for treatment of hepatitis C infection. N Engl J Med. 2009;361:580-593.

Costiniuk CT, Camacho F, Cooper CL. Erythropoiesis-stimulating agent use for anemia induced by interferon-ribavirin
treatment in patients with hepatitis C virus infection is not associated with increased rates of cardiovascular disease,
thrombosis, malignancy or death. Clin Infect Dis. 2008;47:198-202.
Anemia in HIV [NOT FDA-APPROVED]

Grossman HA, Goon B, Leitz G, and the 010 Study Group. Once-weekly epoetin alfa dosing is as effective as three timesweekly dosing in increasing hemoglobin levels and is associated with improved quality of life in anemic HIV-infected
patients. J Acquir Immune Defic Syndr. 2003;34(4):368-378.

Abrams DI, Steinhart C, Frascino R. Epoetin alfa therapy for anaemia in HIV-infected patients: impact on quality of life.
Int J STD AIDS. 2000;11(10):659-665.

Saag MS, Bowers P, Leitz GJ, et al. Once-weekly epoetin alfa improves quality of life and increases hemoglobin in anemic
HIV+ patients. AIDS Res Hum Retroviruses. 2004;20(10):1037-1045.

Marti-Carvajal AJ Sola I.
Treatment for anemia in people with AIDS.
Cochrane Database Syst Rev.
2001;24;(1):CD004776.
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10
epoetin alfa injection (Procrit, Epogen)

Levine AM, Salvato P, Leitz, GJ, and the CHAMPS 2 study group. Efficacy of epoetin alfa administered every 2 weeks to
maintain hemoglobin and quality of life in anemic HIV-infected patients. AIDS Res Hum Retroviruses. 2008;28(2):131139.

Volberding PA, Levine AM, Dieterich D, et al, for the anemia in HIV working group. Anemia in HIV infection: clinical
impact and evidence-based management strategies. Clin Infect Dis. 2004;38(10):1454-1463.
Anemia in ulcerative colitis [NOT FDA-APPROVED]

Gasche C, Dejaco C, Waldhoer T, et al. Intravenous iron and erythropoietin for anemia associated with Crohn disease. A
randomized, controlled trial. Ann Intern Med. 1997;126:782-787.

Schreiber S, Howaldt S, Schnoor M, et al. Recombinant erythropoietin for the treatment of anemia in inflammatory bowel
disease. N Engl J Med. 1996;334:619-623.

Gasche C, Dejaco C, Reinisch W, et al. Sequential treatment of anemia in ulcerative colitis with intravenous iron and
erythropoietin. Digestion. 1999;60:262-267.

Gisbert JP, Gomollon F. Common misconceptions in the diagnosis and management of anemia in inflammatory bowel
disease. Am J Gastroenterol. 2008;103:1299-1307.
Anemia in rheumatoid arthritis [NOT FDA-APPROVED]

Pincus T, Olsen NJ, Russell IJ, et al. Multicenter study of recombinant human erythropoietin in correction of anemia in
rheumatoid arthritis. Am J Med. 1990;89:161-168.

Peeters HRM, Jongen-Lavrencic M, Bakker CH, et al. Recombinant human erythropoietin improves health-related quality
of life in patients with rheumatoid arthritis and anaemia of chronic disease; utility measures correlate strongly with disease
activity measures. Rheumatol Int. 1999;18:201-206.

Gudbjörnsson B, Hällgren R, Wide L, et al. Response of anaemia in rheumatoid arthritis to treatment with subcutaneous
recombinant human erythropoietin. Ann Rheum Dis. 1992;51:747-752.

Murphy EA, Bell AL, Wojtulewski J, et al. Study of erythropoietin in treatment of anaemia in patients with rheumatoid
arthritis. BMJ. 1994;309:1337-1338.

Nordstrom D, Lindroth Y, Marsal L, et al. Availability of iron and degree of inflammation modifies the response to
recombinant human erythropoietin when treating anemia of chronic disease in patients with rheumatoid arthritis. Rheumatol
Int. 1997;17(2):67-73.

Kaltwasser JP, Kessler U, Gottschalk R, et al. Effect of recombinant human erythropoietin and intravenous iron on anemia
and disease activity in rheumatoid arthritis. J Rheumatol. 2001;28(11):2430-2436.
Anemia in heart failure [NOT FDA-APPROVED]

Anand IS. Anemia and chronic heart failure. Implications and treatment options. J Am Coll Cardiol. 2008;52:501-511.

Mancini DM, Katz SD, Lang CC, et al. Effect of erythropoietin on exercise capacity in patients with moderate to severe
chronic heart failure. Circulation. 2003;107(2):294-299.

Caiola K, Cheng JWM. Use of erythropoietin in heart failure management. Ann Pharmacother. 2004;38:2145-2149.

Mak G, Murphy NF, McDonald K. Anemia in heart failure: to treat or not to treat? Curr Treat Options Cardiovasc Med.
2008;10(6):455-464.

Silverberg DS, Wexler D, Sheps D, et al. The effect of correction of mild anemia in severe, resistant congestive heart failure
using subcutaneous erythropoietin and intravenous iron: a randomized controlled study. J Am Coll Cardiol.
2001;37(7):1775-1780.

Silverberg DS, Wexler D, Blum M, et al. The use of subcutaneous erythropoietin and intravenous iron for the treatment of
anemia of severe, resistant congestive heart failure improves cardiac and renal function and functional cardiac class, and
markedly reduces hospitalizations. J Am Coll Cardiol. 2000;35(7):1737-1744.

Hunt SA, Abrahan WT, Chin MH, et al. 2009 focused update incorporated into the ACC/AHA 2005 guidelines for the
diagnosis and management of heart failure in adults. A report of the American College of Cardiology Foundation/American
Heart Association Task Force on Practice Guidelines Developed in Collaboration with the International Society for Heart
and Lung Transplantation. J Am Coll Cardiol. 2009;53(15):e1-e90.
Aplastic anemia [NOT FDA-APPROVED]

Bessho M, Hirashima K, Asano S, et al. Treatment of the anemia of aplastic anemia patients with recombinant human
erythropoietin in combination with granulocyte colony-stimulating factor: a multicenter randomized controlled study.
Multicenter Study Group. Eur J Haematol. 1997;58:265-272.

Shao Z, Chu Y, Zhang Y, et al. Treatment of severe aplastic anemia with an immunosuppressive agent plus recombinant
human granulocyte-macrophage colony-stimulating factor and erythropoietin. Am J Hematol. 1998;59(3):185-191.

Yonekura S, Kawada H, Watanabe S, et al. Hematologic response in patients with aplastic anemia after long-term
administration of recombinant human granulocyte colony-stimulating factor and erythropoietin.
Clin Ther.
1997;19(6):1394-1407.
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11
epoetin alfa injection (Procrit, Epogen)

Marsh JC, Ball SE, Darbyshire P, et al. Guidelines for the diagnosis and management of acquired aplastic anaemia. Br J
Haematol. 2003;123(5):782-801.

Imamura M, Kobayashi M, Kobayashi S, et al. Combination therapy with recombinant human granulocyte colonystimulating factor and erythropoietin in aplastic anemia. Am J Hematol. 1995;48:29-33.
Anemia in systemic lupus erythematosus [NOT FDA-APPROVED]

Giannouli S, Voulgarelis M, Ziakas PD, Tziousfas AG. Anaemia in systemic lupus erythematosus: from pathophysiology to
clinical assessment. Ann Rheum Dis. 2006;65:144-148.

Hebert LA, Birmingham DJ, Shen XP, et al. Effect of recombinant erythropoietin therapy on autoimmunity in systemic
lupus erythematosus. Am J Kid Dis. 1994;24(1):25-32.
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Bradbury BD, Danese MD, Gleeson M, Critchlow CW. Effect of epoetin alfa dose changes on hemoglobin and mortality in
hemodialysis patients with hemoglobin levels persistently below 11 g/dL. Clin J Am Soc Nephrol. 2009;4:630-637.

Cremieux P, Vekeman F, Lefebvre P. Dose conversion and cost effectiveness of erythropoietin therapies in chemotherapyrelated anemia: a Canadian application. J Oncol Pharm Pract. 2006;12(3):165-178.
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Duh MS, Mody SH, McKenzie RS, et al. Dosing patterns and costs of erythropoietic agents in patients with chronic kidney
disease not on dialysis in managed care organizations. Clin Ther. 2006;28(9):1443-1450.
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Ehrenreich H, Weissenborn K, Prange H, et al, for the EPO Stroke Trial Group. Recombinant human erythropoietin in the
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children with cancer. Pediatr Blood Cancer. 2009;53:7-12.
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and anemia treated with epoetin alfa or darbepoetin alfa: a retrospective cohort study. Clin Ther. 2007;29(9):2010-2021.
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Papatheofanis F, Smith C, Mody S, et al. Dosing patterns, hematologic outcomes, and costs of erythropoietin agents in
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CKD patients with anemia. Clin J Am Soc Nephrol. 2009. Sept 17 [Epub ahead of print].
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Phrommintikul A, Haas SJ, Elsik M, Krum H. Mortality and target haemoglobin concentrations in anaemic patients with
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Pfeffer MA, Burdmann EA, Chen CY, et al, on behalf of the TREAT Investigators. Baseline characteristics with the trial to
reduce cardiovascular events with Aranesp therapy (TREAT). Am J Kidney Dis. 2009;54:59-69.
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chemotherapy-related anemia. A meta-analysis. Clin Drug Invest. 2005;25(1):33-48.
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Schneider JK, Gardner DK, Cordero L. Use of recombinant human erythropoietin and risk of severe retinopathy in
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