Neonatal Intensive Care Drug Manual

Support to maintain/ accelerate erythropoiesis

Augmenting haemoglobin level

To decrease the need for RBC transfusions in extremely low birth weight infants

Needs concomitant iron therapy (3-6 mg/kg/day). Refer to Iron formulary for further guidance.

ECMO – No information.

Renal impairment – No information.

Hepatic impairment – No information.

Draw up 0.5 mL (1000 U) EPO and add 4.5 mL of 0.9% sodium chloride to make a final volume of 5 mL with a final concentration of 100 U/mL solution.

IV injection over 1-2 minutes using the proximal IV bung

Full blood count and reticulocyte count weekly.

Neutropaenia and thrombocytosis.

Transient erythema at site of SC injection.

Diarrhoea, vomiting, pyrexia

Ohlsson et al 2020 Cochrane review evaluated 34 studies enrolling 3643 infants.(6) While early administration of ESAs reduced the use of red blood cell (RBC) transfusions, there was a moderate heterogeneity among the included studies and the quality of the evidence was low. The volume of RBCs transfused, and donor exposure were also reduced but reductions were small and were likely to be of limited clinical importance. There was no significant difference in the rate of severe ROP or mortality. There was a significant reduction in the incidence of severe IVH, PVL and NEC. Neurodevelopmental outcomes varied in the studies.

Aher et al 2020 Cochrane review evaluated 31 studies and 1651 preterm infants.(7) Most studies in the trial included small sample size. There was moderate heterogeneity and the quality of evidence was very low. There was a significant reduction in the use of one or more transfusions, but no significant reduction in the total volume (mL/kg) of blood transfused per infant. There was a trend in increased of ROP. There were no significant differences in other clinical outcomes including mortality and necrotising enterocolitis. Long-term neurodevelopmental outcomes were not reported.

Subgroup analysis by Ohlsson et al showed both low and high dose had similar reduction in the use of one or more transfusions. (Low dose: typical RR 0.77, 95% CI 0.65 to 0.91 versus high dose: typical RR 0.79, 95% CI 0.74 to 0.86)(6)

Subgroup analysis by Ohlsson et al showed the following: High dose iron supplementation with either low or high dose EPO therapy showed similar reduction in the use of one or more RBC transfusions. Low dose iron supplementation with high dose EPO therapy significant reduction, but low dose iron and low dose EPO therapy showed no significant reduction in the use of one or more RBC transfusions.(6)

ANMF consensus group adapted EPO dosing schedule of European Multicenter Erythropoietin Beta Study Group.(1, 2)

Both low (≤5 mg/kg/day) and high (>5 mg/kg/day) dose ion supplementation show similar reduction in the number of one or more transfusions with high dose EPO dosing schedule chosen in this formulary.(6)

2. Maier RF, Obladen M, Scigalla P, Linderkamp O, Duc G, Hieronimi G, et al. The effect of epoetin beta (recombinant human erythropoietin) on the need for transfusion in very-low-birth-weight infants. New England Journal of Medicine. 1994;330(17):1173-8.

3. Avent M, Cory B, Galpin J, Ballot D, Cooper P, Sherman G, et al. A comparison of high versus low dose recombinant human erythropoietin versus blood transfusion in the management of anaemia of prematurity in a developing country. Journal of tropical pediatrics. 2002;48(4):227-33.

4. Carnielli V, Montini G, Da Riol R, Dall'Amico R, Cantarutti F. Effect of high doses of human recombinant erythropoietin on the need for blood transfusions in preterm infants. The Journal of pediatrics. 1992;121(1):98-102.

5. Carnielli VP, Da Riol R, Montini G. Iron supplementation enhances response to high doses of recombinant human erythropoietin in preterm infants. Archives of Disease in Childhood-Fetal and Neonatal Edition. 1998;79(1):F44-F8.

6. Ohlsson A, Aher SM. Early erythropoiesis‐stimulating agents in preterm or low birth weight infants. Cochrane Database of Systematic Reviews. 2020(2).

7. Aher SM, Ohlsson A. Late erythropoiesis‐stimulating agents to prevent red blood cell transfusion in preterm or low birth weight infants. Cochrane Database of Systematic Reviews. 2020(1).