Dose and Administration

1.  250 units/kg/dose two-times per week (Monday/Friday) SC.  Total weekly dose 500 units/kg.
     Continue for 4-6 weeks.

• Please chart appropriate generic name.  The particular preparation in use at present is Recormon (Epoetin beta).
• Although other preparations (Trade name: Eprex - Generic name: Epoetin alpha) are available, they are not currently in use in National Women's NICU.

Indications

1. Prevention of blood transfusion in the treatment of anaemia of prematurity (reduced reticulocyte count, normochromic, normocytic, no haemolysis) in infants whose parents are unwilling to give consent for the administration of blood products (see Guidelines for Red Blood Cell Transfusion).

Contraindications and Precautions

1. Prescription of erythropoietin should be discussed with the parents and a verbal consent for treatment needs to be obtained.  A record of this discussion should be documented in the clinical record.
2. Parents should be informed of potential risks associated with the administration of erythropoietin.

Clinical Pharmacology

Erythropoietin is a natural glycoprotein produced primarily in the kidneys which stimulates red blood cell production. During fetal life it is mostly produced in the liver. Extremely premature infants experience a lack of erythropoietin and therefore reduced erythropoiesis. With administration of exogenous erythropoietin red blood cell production is stimulated. Historically it has been shown to reduce the number of blood transfusions, but not within the first two weeks of life. It also has not been shown to avoid transfusions altogether. It seems to be safe, but not cost effective. The aim of exogenous administration of erythropoietin is to avoid blood transfusions and/or to reduce donor exposure). At the same time measures to reduce blood loss (avoid unnecessary blood tests, development of small volume blood tests) should be initiated and blood transfusions protocols should be adhered to.

Interactions

1. No known interactions

Possible Adverse Effects

1. Iron deficiency (which can be prevented by ensuring adequate supplementation).
2. Neutropenia (self-correcting after stopping treatment) may occasionally occur.
3. Thrombocytopenia
4. Thrombocytosis
5. Hypertension
6. Early use has been associated with more severe retinopathy of prematurity.

Special Considerations

1. There are a number of Cochrane systematic reviews evaluating the efficacy of erythropoietin in premature infants.
   • Early use (<8 days) reduces the use of one or more RBC transfusions, the volume of RBC transfused, and the number of donors and transfusions the infant is exposed.  Reductions in these outcomes are small and are of limited clinical importance.  Of some concern, this review demonstrated a significant increase in the incidence of Stage 3 (or greater) ROP when compared to a group of infants receiving placebo.⁸   Early use is also associated with an increased risk of ROP when compared to late use.⁹
   • Late administration (>7 days) similarly reduces the use of one or more RBC transfusions, the number of RBC transfusions per infant and the total volume of RBC transfused per infant. The clinical importance of the results for the latter two outcomes is marginal (<1 transfusion per infant and 7 ml/kg of transfused RBC).¹⁰
2. Strategies for reducing blood loss and decreasing donor exposure in preterm infants should be utilised in preference to erythropoietin use.  These include (but are not limited to):
   • Minimising blood loss around the time of delivery
   • Delayed cord clamping
   • Reducing unnecessary blood sampling
   • Adherence to blood transfusion guidelines
   • Use of "multipacks" from a single donor
3. For those infants receiving erythropoietin, use in conjunction with