epoetin-alfa and Weight-Gain

This study examined the safety, pharmacodynamic (PD), and pharmacokinetic (PK) biosimilarity of the human recombinant erythropoietin (EPO) products ior(®) EPOCIM and Eprex(®) following a 28-day repeated intravenous dose administration in male and female Sprague-Dawley rats with a 14-day recovery period. Safety profiling was based on clinical observations, clinical pathology, and pathology findings for control rats dosed with vehicle and rats dosed either with 30, 300, and 600 I.U./kg of ior(®) EPOCIM or 600 I.U. of Eprex(®) . Adverse findings for both ior(®) EPOCIM and Eprex(®) were similar and were a consequence of thrombotic events (ulcerative skin lesions, swollen hock joints/lameness, stomach ulcers) and decreased body weight gains, all known adverse reactions to this class of drug in rats. With the exception of stomach ulcers, all other adverse findings were fully reversible. Neither drug stimulated the production of antidrug antibodies. As expected, ior(®) EPOCIM and Eprex(®) both increased reticulocyte, red blood cell, hemoglobin, and hematocrit levels in rats. The PK of EPO following dosing with ior(®) EPOCIM was well behaved and consistent with the literature. The results of this study imply that ior(®) EPOCIM and Eprex(®) had safety profiles, PD responses, and toxicokinetic profiles that were biosimilar.

Topics: Administration, Intravenous; Animals; Biosimilar Pharmaceuticals; Chemistry, Pharmaceutical; Epoetin Alfa; Erythropoietin; Female; Hematinics; Male; Rats, Sprague-Dawley; Recombinant Proteins; Risk Assessment; Therapeutic Equivalency; Thrombosis; Toxicokinetics; Weight Gain

Erythropoietin (Epo) is a pleotropic cytokine with several nonhematopoietic tissue effects. High-dose Epo treatment-mediated effects on body weight, fat mass and glucose tolerance have recently been reported, thus extending its pleotropic effects to fat and glucose metabolism. However, the exact dose range of Epo treatment required for such effects remains unidentified to date. We investigated Epo dosage effect (up to 1000 U/kg) on hematocrit, body weight, body composition, glucose metabolism, food intake, and physical activity, during high-fat diet-induced obesity. We report that Epo doses (1000, 600, 300, and 150 U/kg) significantly reduced body weight gain and fat mass, while, only Epo doses of 300 U/kg and higher significantly affected glucose tolerance. None of the tested Epo doses showed any detectable effects on food intake, and only 1000 U/kg dose significantly increased physical activity, suggesting that these parameters may only be partially responsible for the metabolic effects of Epo treatment.

Topics: Adiposity; Animals; Diet; Dietary Fats; Dose-Response Relationship, Drug; Epoetin Alfa; Erythropoietin; Feeding Behavior; Glucose; Hematocrit; Humans; Male; Mice; Mice, Inbred C57BL; Motor Activity; Obesity; Recombinant Proteins; Weight Gain

To evaluate the efficacy of darbepoetin alfa 200 microg subcutaneously every 2 weeks after therapeutic substitution for epoetin alfa.. Retrospective multicenter chart review.. Three US Oncology-affiliated outpatient sites.. Three hundred thirty anemic patients with nonmyeloid malignancies, of whom 174 had been treated previously with epoetin alfa (switched group) and 156 had not been treated recently with epoetin alfa (naive group).. Therapeutic substitution with darbepoetin alfa was started according to the US Oncology Pharmacy and Therapeutics Committee's recommended dosing guidelines: anemic patients with cancer received a starting dosage of darbepoetin alfa 200 microg every 2 weeks regardless of whether or not they had previously received epoetin alfa. Hematologic and darbepoetin alfa usage data were abstracted from consecutive medical records dated from May 2002-March 2003.. Median exposure to darbepoetin alfa was 10 weeks (25th quartile 6 wks, 75th quartile 17 wks) and 10 weeks (25th quartile 5 wks, 75th quartile 18 wks) for the naive and switched groups, respectively. The week before the switch to darbepoetin alfa, the 174 patients receiving epoetin alfa were administered the following weekly doses: less than 40,000 U (9%), 40,000 U (50%), or 45,000-90,000 U (41%). Mean hemoglobin level increased from baseline (wk 0) in both the naive and switched groups. The proportion of patients receiving a red blood cell transfusion in the darbepoetin alfa treatment phase was low (15% in each group). No variation in transfusion rates was observed across weight categories in patients who received a fixed dosage of darbepoetin alfa. Darbepoetin alfa was well tolerated. A detailed usage algorithm was validated by these results and is being used in these three US Oncology-affiliated practices.. A darbepoetin alfa starting dosage of 200 microg subcutaneously every 2 weeks administered according to US Oncology-recommended dosing guidelines is effective in treating chemotherapy-induced anemia in both epoetin alfa-naive patients and those switched from epoetin alfa.

Topics: Aged; Anemia; Antineoplastic Agents; Darbepoetin alfa; Drug Administration Schedule; Epoetin Alfa; Erythrocyte Transfusion; Erythropoietin; Female; Hemoglobins; Humans; Injections, Subcutaneous; Male; Neoplasms; Practice Guidelines as Topic; Recombinant Proteins; Retrospective Studies; Therapeutic Equivalency; Time Factors; Weight Gain