Reduced dosing of enoxaparin for venous thromboembolism in overweight and obese adolescents: a single institution retrospective review

Hoffman, Stephanie; Braunreiter, Chi

doi:10.1002/rth2.12032

Cited by 5 publications

(14 citation statements)

References 29 publications

(39 reference statements)

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“…[19][20][21][22][23][24] The mean initial starting dose was 1 mg/kg twice daily, with a mean final dose of 0.84 mg/ kg twice daily. Four studies titrated therapy to a targeted anti-factor Xa range of 0.5 to 1.0 IU/mL, [21][22][23][24] whereas 2 studies did not adjust dosing throughout the period. 19,20 Four studies consisting of 96 pediatric patients with obesity focused on the use of prophylactic doses of enoxaparin.…”

Section: Resultsmentioning

confidence: 99%

“…Five patients from 2 studies had described thrombotic progression. 16,21 Three thrombotic events occurred in a treatment study, and 2 occurred in a prophylactic study. Nine patients had documented minor bleeding events.…”

Section: Resultsmentioning

confidence: 99%

“…One study using enoxaparin for treatment described thrombotic progression in 3 patients even while achieving therapeutic anti-Xa measurements. 21 One patient was positive for the lupus anticoagulant, which has been shown to increase the prothrombin time in vitro but paradoxically cause more thrombotic events in vivo. 33 There has been some controversy over the use of anti-Xa measurements on whether it should guide the proper dosing of LMWHs.…”

Section: Discussionmentioning

confidence: 99%

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Low-Molecular-Weight Heparin and Fondaparinux Use in Pediatric Patients With Obesity

2020

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Objective: The objective of this study is to comprehensively review the efficacy and safety data of low-molecular-weight heparins (LMWHs) and fondaparinux in pediatric patients with obesity. Data Sources: A comprehensive literature search of PubMed, SCOPUS, CINAHL, Academic Search Complete, PsycInfo, Cochrane Library, and Web of Science databases was conducted (1900 to July 2020). Search terms utilized included LMWH, low-molecular-weight heparin, enoxaparin, dalteparin, tinzaparin, fondaparinux, pediatric, child, children, obese, obesity, overweight. No limits or timeline restrictions were imposed. Study Selection and Data Extraction: Studies that reported pediatric patients with described overweight or obesity and utilized LMWHs or fondaparinux were considered. Data Synthesis: Of 207 studies screened, 12 were included. Average dose reductions of 12.9% to 37.3% from the starting dose were observed with treatment indications of enoxaparin and increased up to 27.3% for prophylactic indications. Trends could not be concluded in the dalteparin and fondaparinux studies. Four thrombotic and 15 bleeding events were reported in the studies. Relevance to Patient Care and Clinical Practice: Pediatric patients with obesity may initially be underdosed or overdosed with enoxaparin compared with children with healthy body weight, depending on the indication. Conclusion: Pediatric patients with obesity may benefit from proactively adjusting enoxaparin dosing on initiation of therapy. Further studies are needed for dalteparin and fondaparinux in these populations. Clinical controversy exists with the relevance of monitoring these high-risk medications for therapeutic and prophylactic indications. Thrombotic and hemorrhagic events were similar to reported adult outcomes.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Low-Molecular-Weight Heparin and Fondaparinux Use in Pediatric Patients With Obesity

2020

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“…Reduced doses (≤ 1 mg/kg/dose every 12 hours, the standard initial treatment dose) of enoxaparin were retrospectively examined as a possible approach to avoid supratherapeutic anti‐Xa levels in 30 adolescents with overweight or obesity receiving the drug twice daily subcutaneously as treatment for VTE (61). TBW‐based initial doses of 0.7 to ≤ 1 mg/kg were effective, whereas VTE progressed in 2 adolescents initially dosed below 0.7 mg/kg.…”

Section: Findings and Discussion By Therapeutic Categorymentioning

confidence: 99%

“…Like T2D across the age spectrum, there may be distinctions between juvenile‐onset and adult‐onset obesity (80,81). In addition, the underlying disease being treated may differ between age groups, as is the case for thrombotic disease and obesity‐associated asthma in adolescents compared with adults (49,61).…”

Section: General Critique and Points Of Special Interestmentioning

confidence: 99%

Dosing Common Medications in Hospitalized Pediatric Patients with Obesity: A Review

Ameer

Weintraub

2020

Obesity

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Medication management in children and adolescents with obesity is challenging because both developmental and pathophysiological changes may impact drug disposition and response. Evidence to date indicates an effect of obesity on drug disposition for certain drugs used in this population. This work identified published studies evaluating drug dosing, pharmacokinetics (PK), and effect in pediatric patients with obesity, focusing on 70 common medications used in a pediatric network of 42 US medical centers. A PubMed search revealed 33 studies providing PK and/or effectiveness data for 23% (16 of 70) of medications, 44% of which have just one study and can be considered exploratory. This work appraising 4 decades of literature shows several promising approaches: greater use of PK models applied to prospective clinical studies, dosing recommendations derived from both PK and safety, and multiyear effectiveness data on drugs for chronic conditions (e.g., asthma). Most studies make dose recommendations but are weakened by retrospective study design, small study populations, and no controls or historic controls. Dosing decisions continue to rely on extrapolating knowledge, including targeting systemic drug exposure typically achieved in adults. Optimal weight‐based dosing strategies vary by drug and warrant prospective, controlled studies incorporating PK and modeling and simulation to complement clinical assessment.

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Use of Real‐World Data and Physiologically‐Based Pharmacokinetic Modeling to Characterize Enoxaparin Disposition in Children With Obesity

Gerhart

Carreño

Loop

et al. 2022

Clin Pharma and Therapeutics

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Dosing guidance for children with obesity is often unknown despite the fact that nearly 20% of US children are classified as obese. Enoxaparin, a commonly prescribed low-molecular-weight heparin, is dosed based on body weight irrespective of obesity status to achieve maximum concentration within a narrow therapeutic or prophylactic target range. However, whether children with and without obesity experience equivalent enoxaparin exposure remains unclear. To address this clinical question, 2,825 anti-activated factor X (anti-Xa) surrogate concentrations were collected from the electronic health records of 596 children, including those with obesity. Using linear mixed-effects regression models, we observed that 4-hour anti-Xa concentrations were statistically significantly different in children with and without obesity, even for children with the same absolute dose (P = 0.004). To further mechanistically explore obesity-associated differences in anti-Xa concentration, a pediatric physiologically-based pharmacokinetic (PBPK) model was developed in adults, and then scaled to children with and without obesity. This PBPK model incorporated binding of enoxaparin to antithrombin to form anti-Xa and elimination via heparinasemediated metabolism and glomerular filtration. Following scaling, the PBPK model predicted real-world pediatric concentrations well, with an average fold error (standard deviation of the fold error) of 0.82 (0.23) and 0.87 (0.26) in children with and without obesity, respectively. PBPK model simulations revealed that children with obesity have at most 20% higher 4-hour anti-Xa concentrations under recommended, total body weight-based dosing compared to children without obesity owing to reduced weight-normalized clearance. Enoxaparin exposure was better matched across age groups and obesity status using fat-free mass weight-based dosing.

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Reduced dosing of enoxaparin for venous thromboembolism in overweight and obese adolescents: a single institution retrospective review

Cited by 5 publications

References 29 publications

Low-Molecular-Weight Heparin and Fondaparinux Use in Pediatric Patients With Obesity

Low-Molecular-Weight Heparin and Fondaparinux Use in Pediatric Patients With Obesity

Dosing Common Medications in Hospitalized Pediatric Patients with Obesity: A Review

Use of Real‐World Data and Physiologically‐Based Pharmacokinetic Modeling to Characterize Enoxaparin Disposition in Children With Obesity

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