Epogen - Clinical Pharmacology

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Zidovudine-treated HIV-infected Patients

Responsiveness to EPOGEN (r) 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 EPOGEN (r) therapy. Patients with endogenous serum erythropoietin levels > 500 mUnits/ mL do not appear to respond to EPOGEN (r) 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 EPOGEN (r) in zidovudine-treated HIV-infected patients is manifested by reduced transfusion requirements and increased hematocrit.

Cancer Patients on Chemotherapy

Anemia in cancer patients may be related to the disease itself or the effect of concomitantly administered chemotherapeutic agents. EPOGEN (r) has been shown to increase hematocrit and decrease transfusion requirements after the first month of therapy (months 2 and 3), in anemic cancer patients undergoing chemotherapy. A series of clinical trials enrolled 131 anemic cancer patients who were receiving cyclic cisplatin-or non cisplatin-containing chemotherapy. Endogenous baseline serum erythropoietin levels varied among patients in these trials with approximate-ly 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 EPOGEN (r) 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 EPOGEN (r) therapy, treatment of patients with grossly elevated serum erythropoietin levels (eg, > 200 mUnits/ mL) is not recommended.

Pharmacokinetics

Intravenously administered EPOGEN (r) is eliminated at a rate consistent with first order kinetics with a circulating half-life ranging from approximately 4 to 13 hours in adult and pediatric patients with CRF. 14-16 Within the therapeutic dose range, detectable levels of plasma erythropoietin are maintained for at least 24 hours. After SC administration of EPOGEN (r) to patients with CRF, peak serum levels are achieved within 5 to 24 hours after administration and decline slowly thereafter. There is no apparent difference in half-life between adult patients not on dialysis whose serum creatinine levels were greater than 3, and adult patients maintained on dialysis.