Once‐daily enoxaparin in pediatric thromboembolism: a dose finding and pharmacodynamics/pharmacokinetics study

O’Brien, Sarah H.; Lee, H.; Ritchey, A. Kim

doi:10.1111/j.1538-7836.2007.02624.x

Cited by 40 publications

(38 citation statements)

References 11 publications

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“…A study of children aged 3 months-16 years who completed 24 h pharmacokinetic sampling showed that clearance of drug was faster and total drug exposure lower than in adults. Most children had sub-therapeutic anti-FXa (<0AE5) at 12 h and half had undetectable levels at 18 h (O'Brien et al, 2007). This contrasts with adult data where therapeutic levels were measurable at 13-18 h with prophylactic levels (0AE1-0AE3 anti-FXa iu/ml) at 24 h (Sanderink et al, 2002).…”

Section: Dosing Lmwhcontrasting

confidence: 52%

Aspects of anticoagulation in children

Payne

2010

Br J Haematol

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SummaryThe number of children receiving anticoagulation is increasing. Thromboembolic events are associated with significant risk of morbidity and mortality although the optimal management of asymptomatic events remains unclear. Specific challenges in paediatrics include the diagnosis of thrombosis, delivery and monitoring of anticoagulation in a wide range of ages from neonates through to adolescents. The development of the haemostatic system as children age results in changing pathophysiology of thrombosis and response to anticoagulation agents. Although registry and observational studies have provided vital information, specific paediatric, prospective anticoagulation studies have been few and limited in design. The result is that much of current practice is extrapolated from adult studies. Traditional anticoagulants have significant limitations. Both heparin and warfarin are in widespread use but many fundamental questions regarding dose, therapeutic range, efficacy and optimum duration have not been fully answered. Alternative agents, such as direct thrombin inhibitors and the selective anti-factor Xa inhibitor fondaparinux, may have advantages for children. Clinical trials in adults and preliminary data in children are promising but caution should be applied until specific paediatric studies have demonstrated safety and efficacy.

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Section: Dosing Lmwhcontrasting

confidence: 52%

Aspects of anticoagulation in children

Payne

2010

Br J Haematol

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“…In 2007 O’Brien et al. reported a non‐compartmental enoxaparin analysis for q24 h dosing derived from 15 children during the acute therapy (after the second enoxaparin administration) [11]. The study found anti‐FXa activity levels to be less than 0.5 IU mL −1 by hour 12 in seven out of eight cases, and defined this anti‐FXa activity as sub‐therapeutic without showing the individual anti‐FXa activity levels.…”

Section: Discussionmentioning

confidence: 99%

Population pharmacokinetics of enoxaparin in infants, children and adolescents during secondary thromboembolic prophylaxis: a cohort study

Trame

Mitchell

Krümpel

et al. 2010

Journal of Thrombosis and Haemostasis

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children and adolescents during secondary thromboembolic prophylaxis: a cohort study. J Thromb Haemost 2010; 8: 1950-8. Summary. Background: Enoxaparin has been extensively studied in adults on its safety and efficacy during prevention of symptomatic thromboembolism when acute anticoagulation or secondary prevention is required as a result of venous thrombosis or stroke. In children, it is still used off-label and little is known about the pharmacokinetics in children. Objectives: The aim of the present study was to evaluate whether a once-or twice-daily dosing regimen would be feasible in children to achieve appropriate plasma levels of enoxaparin. Patients/methods: A population pharmacokinetic model was developed using anti-factor (F)Xa activity data from 126 children (median age: 5.9 years) receiving enoxaparin either as a once-or twice-daily dosing regimen. Results: A two-compartment model was adequate for describing the enoxaparin kinetics. Body weight proved to be the most predictive covariate for clearance and central volume of distribution: clearance 15 mL h )1 kg . Interindividual variability was found to be 54% for clearance and 42% for volume of distribution. Conclusion: The model is capable of describing all age groups and dosing levels of our population and predicts 12 h and 24 h enoxaparin activities sufficiently. According to our results, a once-daily enoxaparin dosing regimen with frequent monitoring is feasible. In 53.2% of the patients the median 24 h trough level was above the desired range of 0.1 IU mL )1 anti-FXa activity for prophylaxis therapy.

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“…A recent study has demonstrated that once daily dosing is feasible for children [37], a significant advantage over the twice daily dosing required with the LMWH compounds [25,38,39]. Additionally, there are data suggesting that fondaparinux may cause less or even no osteoporosis [22,40,41].…”

Section: New Anticoagulant Agentsmentioning

confidence: 99%

Current and future management of pediatric venous thromboembolism

Kerlin

2012

American J Hematol

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Venous thromboembolism (VTE) is an increasingly common complication encountered in tertiary care pediatric settings. The purpose of this review is to summarize the epidemiology, current and emerging pharmacotherapeutic options, and management of this disease. Over 70% of VTE occur in children with chronic diseases. Although they are seen in children of all ages, adolescents are at greatest risk. Pediatric VTE is associated with an increased risk of in-hospital mortality; recurrent VTE and post-thrombotic syndrome are commonly seen in survivors. In recent years, anticoagulation with low molecular weight heparin has emerged as the mainstay of therapy, but compliance is limited by its onerous subcutaneous administration route. New anticoagulants either already approved for use in adults or in the pipeline offer the possibility of improved dose stability and oral routes of administration. Current recommended anticoagulation course durations are derived from very limited case series and cohort data, or extrapolations from adult literature. However, the pathophysiologic underpinnings of pediatric VTE are dissimilar from those seen in adults and are often variable within groups of pediatric patients. Clinical studies and trials in pediatric VTE are underway which will hopefully improve the quality of evidence from which therapeutic guidelines are derived.

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Once‐daily enoxaparin in pediatric thromboembolism: a dose finding and pharmacodynamics/pharmacokinetics study

Cited by 40 publications

References 11 publications

Aspects of anticoagulation in children

Aspects of anticoagulation in children

Population pharmacokinetics of enoxaparin in infants, children and adolescents during secondary thromboembolic prophylaxis: a cohort study

Current and future management of pediatric venous thromboembolism

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