Chronic Renal Failure Patients

Endogenous production of erythropoietin is normally regulated by the level of tissue oxygenation. Hypoxia and anemia generally increase the production of erythropoietin, which in turn stimulates erythropoiesis.² In normal subjects, plasma erythropoietin levels range from 0.01 to 0.03 Units/mL and increase up to 100- to 1000-fold during hypoxia or anemia.² In contrast, in patients with chronic renal failure (CRF), production of erythropoietin is impaired, and this erythropoietin deficiency is the primary cause of their anemia.^3,4

Chronic renal failure is the clinical situation in which there is a progressive and usually irreversible decline in kidney function. Such patients may manifest the sequelae of renal dysfunction, including anemia, but do not necessarily require regular dialysis. Patients with end-stage renal disease (ESRD) are those patients with CRF who require regular dialysis or kidney transplantation for survival.

PROCRIT® has been shown to stimulate erythropoiesis in anemic patients with CRF, including both patients on dialysis and those who do not require regular dialysis.^4-12 The first evidence of a response to the three times weekly (TIW) administration of PROCRIT® is an increase in the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks.^4,5 Because of the length of time required for erythropoiesis — several days for erythroid progenitors to mature and be released into the circulation — a clinically significant increase in hematocrit is usually not observed in less than 2 weeks and may require up to 6 weeks in some patients. Once the hematocrit reaches the suggested target range (30% to 36%), that level can be sustained by PROCRIT® therapy in the absence of iron deficiency and concurrent illnesses.

The rate of hematocrit increase varies between patients and is dependent upon the dose of PROCRIT®, within a therapeutic range of approximately 50 to 300 Units/kg TIW.⁴ A greater biologic response is not observed at doses exceeding 300 Units/kg TIW. ⁶ Other factors affecting the rate and extent of response include availability of iron stores, the baseline hematocrit, and the presence of concurrent medical problems.

Zidovudine-treated HIV-infected Patients

Responsiveness to PROCRIT® in HIV-infected patients is dependent upon the endogenous serum erythropoietin level prior to treatment. Patients with endogenous serum erythropoietin levels ≤ 500 mUnits/mL, and who are receiving a dose of zidovudine ≤ 4200 mg/week, may respond to PROCRIT® therapy. Patients with endogenous serum erythropoietin levels > 500 mUnits/mL do not appear to respond to PROCRIT® therapy. In a series of four clinical trials involving 255 patients, 60% to 80% of HIV-infected patients treated with zidovudine had endogenous serum erythropoietin levels ≤ 500 mUnits/mL.

Response to PROCRIT® in zidovudine-treated HIV-infected patients is manifested by reduced transfusion requirements and increased hematocrit.

Cancer Patients on Chemotherapy

A series of clinical trials enrolled 131 anemic cancer patients who received PROCRIT® TIW and who were receiving cyclic cisplatin- or non cisplatin-containing chemotherapy. Endogenous baseline serum erythropoietin levels varied among patients in these trials with approximately 75% (n = 83/110) having endogenous serum erythropoietin levels ≤ 132 mUnits/mL, and approximately 4% (n = 4/110) of patients having endogenous serum erythropoietin levels > 500 mUnits/mL. In general, patients with lower baseline serum erythropoietin levels responded more vigorously to PROCRIT® than patients with higher baseline erythropoietin levels. Although no specific serum erythropoietin level can be stipulated above which patients would be unlikely to respond to PROCRIT® therapy, treatment of patients with grossly elevated serum erythropoietin levels (eg, > 200 mUnits/mL) is not recommended.

Pharmacokinetics

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