The parenteral administration of any biologic product should be attended by appropriate precautions in case allergic or other untoward reactions occur. In clinical trials, while transient rashes were occasionally observed concurrently with erythropoietin therapy; no serious allergic or anaphylactic reactions were reported.
The safety and efficacy of erythropoietin therapy have not been established in patients with a known history of a seizure disorder or underlying hematologic disease (e.g., sickle cell anemia, myelodysplastic syndromes, or hypercoagulable disorders).
Hematology: Exacerbation of porphyria has been observed rarely in patients with CRF treated with erythropoietin. Erythropoietin should be used with caution in patients with known porphyria.
Delayed or Diminished Response: If the patient fails to respond or to maintain a response to doses within the recommended dosing range, the following etiologies should be considered and evaluated: Iron deficiency: Virtually all patients will eventually require supplemental iron therapy; Underlying infectious, inflammatory, or malignant processes; Occult blood loss; Underlying hematologic diseases (i.e., thalassemia, refractory anemia, or other myelodysplastic disorders); Vitamin deficiencies: Folic acid or vitamin B12; Hemolysis; Aluminum intoxication; Osteitis fibrosa cystica.
Iron Evaluation: Transferrin saturation should be at least 20% and ferritin should be at least 100 ng/mL. Prior to and during erythropoietin therapy, the patient's iron status, including transferrin saturation (serum iron divided by iron binding capacity) and serum ferritin, should be evaluated. Virtually all patients will eventually require supplemental iron to increase or maintain transferrin saturation to levels, which will adequately support erythropoiesis stimulated by erythropoietin.
Carcinogenesis, Mutagenesis, And Impairment Of Fertility: Carcinogenic potential of erythropoietin has not been evaluated. Erythropoietin does not induce bacterial gene mutation (Ames Test), chromosomal aberrations in mammalian cells, micronuclei in mice, or gene mutation at the HGPRT locus. In female rats treated IV with erythropoietin, there was a trend for slightly increased fetal wastage at doses of 100 and 500 Units/kg.