Enoxaparin Dosing Requirements
Two recent papers have confirmed earlier work demonstrating the need for higher enoxaparin doses in infants and young children.[4–5] In another study conducted at the University of Melbourne Royal Children's Hospital, Ignjatovic and colleagues reviewed the records of 233 patients (ages 3 days to 16 years) treated with enoxaparin between October 2003 and July 2007.[4] Of those patients, 140 had at least one anti-Factor Xa (anti-Xa) assay performed during treatment and were included in the analysis. All patients received enoxaparin 0.5–0.75 mg/kg twice daily. The majority of patients (81%) were being treated with enoxaparin for a diagnosed clot, with the remaining 19% receiving enoxaparin as prophylaxis. Use of anti-Xa monitoring was more frequent in patients under a year of age compared to older children and in patients treated for more than 60 days compared to those with shorter treatment courses (both comparisons, p < 0.05). Only 55 patients (39%) had an anti-Xa value within the target range of 0.5–1.0 IU/mL. Seventy-three patients (52%) were subtherapeutic and 12 (9%) had values above 1.0 IU/mL. More infants than older children were subtherapeutic on their initial enoxaparin regimen (p < 0.05).
The average enoxaparin dose required to achieve a therapeutic anti-Xa in patients being treated for a clot was significantly higher in the younger age groups than in the two older groups, with a mean dose of 1.59 ± 0.47 mg/kg in the patients < 2 months, 1.48 ± 0.47 mg/kg for those 2 months-1 year, and 1.19 ± 0.22 mg/kg in those 1–5 years, compared to 0.98 ± 0.18 mg/kg in children 6–10 years and 0.98 ± 0.13 mg/kg in the 11–16 year old children (p < 0.05). While age played a significant role in enoxaparin dose response, the authors observed that there was no difference in dosing requirements between infants born prematurely and those born at term. Forty-one patients (29%) experienced minor bleeding, but only one case of major bleeding occurred. In the 73 patients for whom an outcome was recorded, 17 (23%) had complete clot resolution, 36 (49%) had partial resolution, 15 (21%) had no change and 5 (7%) had clot extension. As in previous studies, the authors concluded that current dosing recommendations are not adequate for patients up to 5 years of age.
Sanchez de Toledo and colleagues found a similar need for higher enoxaparin doses in infants and young children in their cardiac intensive care unit.[5] Thirty-one patients were included in the retrospective study, ranging in age from birth to 2 years; 25 (81%) had recently undergone cardiac surgery. Twenty-one patients (68%) were receiving treatment doses and the remainder were receiving prophylaxis. For analysis, the patients were divided into two groups: younger patients (0–2 months of age) and older patients.
Both age groups required an increase in their enoxaparin doses to achieve an anti-Xa value within the target range. In the younger patients, the mean enoxaparin dose increased from 1 mg/kg to 1.87 mg/kg in those receiving prophylaxis and from 1.5 mg/kg to 2.37 mg/kg in those receiving treatment (therapeutic) doses (p < 0.02 for both). In the older patients, the dose increase in the prophylaxis group, from 0.73 mg/kg to 1.06 mg/kg was not statistically significant. There was a significant increase, however, in the treatment doses, from 1.23 mg/kg to 1.82 mg/kg (p = 0.002). The average number of dosage adjustments required to achieve an appropriate anti-Xa value was similar in the two age groups: 2.8 ± 1.2 in the younger patients and 1.9 ± 1.7 in the older patients. No difference in dosing requirements was found between those patients who received direct subcutaneous injection and those using an Insuflon® device. No bleeding complications were identified.
A third study, published last year in the Journal of Thrombosis and Haemostasis, provides an interesting variation on traditional enoxaparin dosing.[6] Using anti-Xa values and dosing information collected from 126 children and young adults (newborn-25 years of age, median 5.9 years), Trame and colleagues developed a population pharmacokinetic model that would allow prediction of anti-Xa activity resulting from both 12- and 24-hour dosing schemes. Their focus was to explore the feasibility of once daily enoxaparin for prophylaxis. Using the model developed, 53% of patients receiving once daily dosing would achieve the anti-Xa goals of 0.3–0.8 IU/mL at 4–6 hours post-dose and 0.1 IU/mL at the end of the dosing interval. Based on their results, the authors propose that once daily dosing may be feasible for some children requiring enoxaparin prophylaxis, provided that anti-Xa monitoring is conducted to ensure adequate anticoagulation.
Pediatr Pharm. 2011;17(9) © 2011 Children's Medical Center, University of Virginia
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