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  Vol. VII, No. IV
  July/August 2004

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The Cleveland Clinic Foundation
Pharmacy and Therapeutics Committee
Automatic Therapeutic Interchange Program
Epoetin alfa (Procrit®) to Darbepoetin alfa (Aranesp)

At the June 2004 meeting, the CCF Pharmacy and Therapeutics Committee deemed epoetin alfa (Procrit®; OrthoBiotech) and darbepoetin alfa (Aranesp™; Amgen) to be therapeutic equivalent products and approved an automatic therapeutic interchange to darbepoetin alfa for chronic anemia of cancer and chemotherapy-induced anemia (CIA) for both outpatients and inpatients. Based on market share contracts, darbepoetin alfa is less expensive than epoetin alfa. The implementation date for the interchange program is October 11, 2004. In the near future, the Pharmacy and Therapeutics Committee will be exploring other patient populations for this interchange, such as patients with chronic renal failure (CRF). In addition, at this time, this interchange program does not affect Epogen® (Amgen), another brand name for epoetin alfa. Epogen® is used in the dialysis area at CCF.

Similar to endogenous erythropoietin, darbepoetin alfa stimulates erythropoiesis. Production of endogenous erythropoietin may be impaired in patients receiving chemotherapy. In cancer patients, erythropoietic agents, including epoetin alfa and darbepoetin alfa, have been shown to decrease the number of patients receiving transfusions, to increase hemoglobin levels, and to improve quality of life. Darbepoetin alfa (5 N-linked CHO chains) has a 3-fold increase in half-life when compared to epoetin alfa (3 N-linked CHO chains). In chronic kidney disease (CKD) patients, darbepoetin alfa administered intravenously has a half-life of 25.3 hours compared to epoetin alfa, which has a half-life of 8.5 hours. In CKD, for subcutaneous (SC) administration of darbepoetin alfa, the half-life is ~49 hours (a similar half-life of darbepoetin administered SC has been shown in cancer patients as well). Darbepoetin alfa, although several fold more biologically active than epoetin alfa, paradoxically was found to have less affinity for the erythropoietin receptors, suggesting the slower clearance of the molecule is a more important determinant of potency and receptor affinity has no or little clinical relevance. The recommended starting dose of darbepoetin alfa for CIA is 200 mcg SC every-other-week or 100 mcg SC once weekly. The dose should be titrated to meet and maintain desired hemoglobin (Hgb) levels.

Safety and Efficacy: Currently available data indicate that darbepoetin alfa is as well tolerated and efficacious as epoetin alfa even when administered less frequently. Studies of erythropoietin therapy in patients with chronic anemia of cancer as well as CIA document response rates ranging from ~60% to 85%. Response rates are defined in two ways: 1) Hgb levels > 12 g/dL or 2) an increase in Hgb of 2 g/dL from baseline. For recommended dose equivalency, see Tables A and B (below).

Internal Data: A retrospective drug use evaluation (DUE) was conducted at the Cleveland Clinic Health System (CCHS) reviewing the use of epoetin alfa and darbepoetin alfa for the management of CIA. The objective of the DUE was to trend usage patterns in the outpatient arena for dosing, dosing interval, hemoglobin levels, number of transfusions, and iron studies. In order to be included in the DUE, patients had to be initiated on epoetin alfa or darbepoetin alfa for at least 3 weeks between July 2002 and July 2003. A total of 114 (n=92 CCF) patients were included in the DUE, 59 epoetin alfa patients and 55 darbepoetin alfa patients. Mean baseline Hgb levels were 9.95 g/dL and 9.80 g/dL in the epoetin alfa- and darbepoetin alfa-treated patients, respectively. In addition, Hgb levels were similar over the course of therapy for both groups. The average duration of therapy was 13.2 weeks and 13.6 weeks in the epoetin alfa- and darbepoetin alfa-treated patients, respectively. A target hemoglobin of > 12 g/dL was reached in 47 patients (41%) overall. More specifically, 23 patients in the epoetin alfa group and 24 patients in the darbepoetin alfa group reached the targeted Hgb level. The most frequent dosing regimens were 40,000 units weekly for epoetin alfa-treated patients and 200 mcg every 2 weeks (or every-other-week) for darbepoetin alfa-treated patients. The number of patients receiving transfusions was similar between the groups, 11 in the epoetin alfa-treated group and 7 in the darbepoetin alfa-treated group. Overall, only 10.5% of patients had iron studies before erythropoietin therapy. Based on data from this CCHS DUE, darbepoetin alfa and epoetin alfa produce similar Hgb levels in patients with CIA. The most common dosing regimens are 40,000 units weekly for epoetin alfa and 200 mcg every 2 weeks for darbepoetin alfa. Overall, in both groups iron studies were not conducted routinely.

Questions regarding this interchange program should be directed to the CCF Department of Pharmacy Drug Information Center (216-444-6456, option #1).

Table A: Dose Equivalency between Epoetin alfa and Darbepoetin alfa in Adult Outpatient Oncology Patients
Epoetin alfa (Units/week) Darbepoetin alfa (mcg/Q 2 weeks)
2,500 - 4,999 25
5,000 - 10,999 50
11,000 - 17,999 80
18,000 - 33,999 120
34,000 - 89,999 200

These are recommended doses. Depending upon each patient's needs and response, dosage adjustments may be required. Based on the patient's response, darbepoetin alfa may be administered as frequently as once every 3 or 4 weeks.

Table B: Dose Equivalency between Epoetin alfa and Dabepoetin alfa in Adult Inpatient Oncology Patients
Epoetin alfa (Units/week) Darbepoetin alfa (mcg/week)
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

These are recommended doses. Depending upon each patient's needs and response, dosage adjustments may be required. Based on the patient's response, darbepoetin alfa may be administered as frequently as once every 3 or 4 weeks.