Population pharmacokinetic of nadroparin calcium (Fraxiparine®) in children hospitalised for open heart surgery

Laporte, Silvy; Mismetti, Patrick; Piquet, Pascal; Doubine, Sylvie; Touchot, Anita; Décousus, Hervé

doi:10.1016/s0928-0987(98)00064-5

Cited by 17 publications

(20 citation statements)

References 13 publications

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“…Pharmacokinetic studies of LMWHs in neonates, infants and children are limited and have been performed for four agents, for example enoxaparin, nadroparin, reviparin‐sodium and tinzaparin, respectively ( Massicotte et al , 1996 , 2003b ; Laporte et al , 1999 ; Punzalan et al , 2000 ; Kuhle et al , 2005 ). The LMWH used, the number of patients enrolled, the time to maximum level and maintenance doses to achieve the target anti‐Xa range of 0.5–1.0 U ml −1 are shown in Table 1.…”

Section: Paediatric Pharmacokinetic Studies On Lmwh and Monitoringmentioning

confidence: 99%

Pharmacokinetics, efficacy, and safety of LMWHs in venous thrombosis and stroke in neonates, infants and children

Nowak‐Göttl

Bidlingmaier

Krümpel

et al. 2008

British J Pharmacology

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Since the early nineties it has been shown that low molecular weight heparin (LMWH) has significant advantages over unfractionated heparin and oral anticoagulants for both the treatment and the prevention of thrombosis, not only in adults, but also in children. The present review was based on an 'EMBASE', 'Medline' and 'PubMed' search including literature published in any language since 1980 on LMWH in neonates, infants and children. It included paediatric pharmacokinetic studies, the use of LMWH in children with venous thrombosis, LMWH administration in paediatric patients with ischaemic stroke, and its use in order to prevent symptomatic thromboembolism in children at risk. An increasing rate of off-label use of LMWH in children has been reported, showing that LMWHs offer important benefits to children with symptomatic thromboembolic events and poor venous access. Two well-conducted pharmacokinetic studies in this age group showed that neonates and younger infants require higher LMWH doses than older children to achieve the targeted anti-Xa levels, due to an increased extra vascular clearance. Recurrent symptomatic thromboses under LMWH occur in approximately 4% of children treated for venous thrombosis, and in 7% of children treated for stroke; major bleed was documented in 3% of children with therapeutic target LMWH anti-Xa levels, whereas minor bleeding was reported in approximately 23% of children receiving either therapeutic or prophylactic doses, respectively. Further randomized controlled trials are recommended to evaluate the optimum duration and application for different LMWH indications in children.

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Section: Paediatric Pharmacokinetic Studies On Lmwh and Monitoringmentioning

confidence: 99%

Pharmacokinetics, efficacy, and safety of LMWHs in venous thrombosis and stroke in neonates, infants and children

Nowak‐Göttl

Bidlingmaier

Krümpel

et al. 2008

British J Pharmacology

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“…An important causative factor to the higher doses of nadroparin in younger patients is the increased clearance compared with adults. 4,24 In the younger patients, especially neonates, effective nadroparin therapy was difficult to achieve starting with the ''adult'' dose of 85.5 IU/kg twice daily: after 1 week, only 25% of the neonates had reached TTR. TTR will probably be reached earlier by increasing the starting dose of nadroparin (eg, 240 IU/kg/d).…”

Section: Discussionmentioning

confidence: 99%

“…1,2 Literature about dosing and safety of LMWHs in children is scarce, only data about prophylactic dosing of nadroparin are available. 3,4 Agespecific guidelines for anticoagulant therapy are necessary as a result of the development of hemostasis, which affects the physiopathology and the response to anticoagulant therapy in children. The purpose of this prospective cohort study is to evaluate the pharmacodynamics and clinical safety of therapeutic doses of nadroparin in pediatric patients with venous thrombosis dosed to achieve anti-Xa activity levels of 0.5 to 1.0 IU/mL in 1 single tertiary center.…”

mentioning

confidence: 99%

Nadroparin Therapy in Pediatric Patients With Venous Thromboembolic Disease

Ommen

Dool²,

Peters³

2008

Journal of Pediatric Hematology/Oncology

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Low-molecular-weight heparins are increasingly used for treatment of pediatric venous thromboembolic disease (VTE). Pediatric data about therapeutic doses of nadroparin are not available. To evaluate pharmacodynamics and safety of therapeutic doses of nadroparin, consecutive patients (age 0 to 18 y) with objectively diagnosed VTE and treated with nadroparin were included in this single center study over a 12-year period. All patients started with 85.5 IU/kg of nadroparin twice daily. The target therapeutic range (TTR) was set at 0.5 to 1.0 anti-Xa IU/mL 4 hours postdose. Safety end points were major bleeding and therapy-related death. A total of 84 patients were enrolled, of whom 8 patients did not undergo measurement of anti-Xa levels. Fifty-four (71%) of 76 patients achieved TTR. The maintenance dose (mean+/-SE) was 448+/-42 IU/kg/d in neonates (<2 mo, n=6), 253+/-22 IU/kg/d in infants (2 mo to 1 y, n=10), 214+/-8 IU/kg/d in children (2 to 11 y, n=13), and 183+/-5 IU/kg/d in adolescents (12 to 18 y, n=25). Neonates required significantly more dose adjustments and time to achieve TTR than adolescents. No major bleeding or therapy-related death occurred. In summary, an age-dependent response to nadroparin exists in pediatric patients. Nadroparin therapy seems to be safe for treatment of pediatric VTE.

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“…They concluded that there were patient characteristics that influenced the PK parameters of nadroparin since the apparent clearance and volume of distribution depended on age and weight. They estimated that for a 10-kg child, clearance was approximately 37 ml/h/kg compared with adults, for whom the max clearance is approximately 12.5 ml/h/kg in young healthy volunteers, and 11.6 ml/h/kg in patients with deep vein thrombosis [16]. This indicates that the PK properties of nadroparin in children are likely different from those in adults and that higher doses are needed in children in order to reach a similar range of anti-Xa levels.…”

Section: Nadroparinmentioning

confidence: 99%

Pharmacokinetic- and pharmacodynamic-based antithrombotic dosing recommendations in children

2012

Expert Review of Clinical Pharmacology

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With the increasing incidence of venous thromboembolic events in children, there has also been a concurrent increase in the use of anticoagulants in children. It is imperative that dosing recommendations of anticoagulants be derived from pharmacokinetic- and pharmacodynamic-based data in children and not simply extrapolated from data based on adults. Medications for children are often based on weight or body surface area, and are often distributed and metabolized differently as well. Furthermore, the hemostatic system in neonates and infants differs from that of older children and adults, and targets for therapy may differ. For these reasons, dosing guidelines for all antithrombotic medications should be based on pharmacokinetic and pharmacodynamic data. The authors reviewed pharmacokinetic and pharmacodynamic studies of anticoagulants in children and make dosing recommendations based on study findings.

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Population pharmacokinetic of nadroparin calcium (Fraxiparine®) in children hospitalised for open heart surgery

Cited by 17 publications

References 13 publications

Pharmacokinetics, efficacy, and safety of LMWHs in venous thrombosis and stroke in neonates, infants and children

Pharmacokinetics, efficacy, and safety of LMWHs in venous thrombosis and stroke in neonates, infants and children

Nadroparin Therapy in Pediatric Patients With Venous Thromboembolic Disease

Pharmacokinetic- and pharmacodynamic-based antithrombotic dosing recommendations in children

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