Hema-Plus Special Precautions

General: Parenteral intake of any biological product must be carefully controlled and care must be taken in cases of allergy or unexpected reactions. Clinical tests showed occasional cases of skin rash. However, no systemic allergic or anaphylactic reactions were observed.
Diminished or delayed response: If the patient fails to respond or maintain a response to doses in the target range, the following etiologies must be observed and evaluated: 1. Iron deficiency. All patients will eventually require additional iron therapy.
2. Underlying infectious, inflammatory or malignant processes.
3. Loss of occult blood.
4. Underlying hematological diseases, e.g., thalassemia, refractory anemia or other myelodysplastic disorders.
5. Vitamins or folic acid deficiency.
6. Hemolysis.
7. Aluminum intoxication.
8. Cystic fibrous osteitis.
9. Secondary hyperparathyroidism.
Hematology: Some very rare cases of patients treated with erythropoietin have shown an exacerbation of porphyry, although there is no evidence of such increase of porphyries metabolites in normal volunteers. Hema-Plus should, however, be used with caution in patients with porphyry.
** Pure Red Cell Aplasia (PRCA): Antibody-mediated pure red cell aplasia (PRCA) were reported after subcutaneous injection of Epoetin treatment for a long time mainly in chronic renal failure patients. Cases were reported in patients with Hepatitis C treated with interferon and ribavirin in combination with Epoetin.
In patients developing lack of efficacy defined by a decrease in haemoglobin with increased need for transfusions, a reticulocyte count should be obtained and typical causes of non-response should be investigated.
If reticulocyte index shows lower than 20000 per microliter or less than 0.5%, with regular level of blood platelet and white blood cell with no other causes, should also be monitored anti-erythropoietin antibodies and bone marrow for diagnosis of the PRCA.
Either unexplained loss of effect (LOE) or PRCA suspected, prompt to discontinue treatment with Hema-Plus. No other ESA therapy should be commenced because of the risk of cross-reaction. Other treatments such as blood perfusion etc should be considered.
Iron assessment: During the treatment with Hema-Plus, an absolute or functional iron deficiency may develop. A functional deficit with normal ferritin values and low transferrin saturation is due to the inability of iron fast mobilization of the store in order to sustain the erythropoiesis rate.
Prior to initiation of therapy the patient's iron stores, including transferrin saturation and ferritin, which should be at least 20% and 100 ng/ml, respectively, should be evaluated. All patients will need an iron supplement.