fondaparinux and Body-Weight

Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Anticholesteremic Agents; Anticoagulants; Antineoplastic Agents; Azetidines; Body Weight; Cannabinoid Receptor Antagonists; Cetuximab; Drug Therapy; Ezetimibe; Fondaparinux; Humans; Hypoglycemic Agents; Insulin; Osteoporosis, Postmenopausal; Piperidines; Polysaccharides; Pyrazoles; Rimonabant; Smoking Cessation; Teriparatide; Thromboembolism

Fondaparinux (FPX), a selective inhibitor of factor Xa, is widely used for the prophylaxis of venous thromboembolism (VTE) after total joint arthroplasty. However, the association between plasma FPX concentration and adverse events and the occurrence of VTE has not been clarified thus far. We aimed to prospectively evaluate these associations by measuring anti-Xa activity of FPX in patients undergoing total hip arthroplasty (THA) and investigate whether factors such as age, body weight, and renal function influence the anti-Xa levels. We enrolled 85 patients who underwent primary THA. All patients received subcutaneous FPX (2.5 mg/day for 14 days) after surgery. Anti-Xa activity was measured on postoperative days 1, 3, 7, and 14. To assess VTE, multidetector row computed tomography was performed in all patients at 1 week after surgery. The median levels of anti-Xa activity increased as follows (medians with 95 % confidence interval): 0.00 (0.00-0.01) mg/L, 0.13 (0.11-0.14) mg/L, 0.19 (0.17-0.20) mg/L, and 0.24 (0.22-0.25) mg/L on postoperative days 1, 3, 7, and 14, respectively. The plasma accumulation of FPX was more likely in patients with renal impairment than in those with normal renal function. In contrast, a poor correlation was observed between the plasma levels of anti-Xa activity and age or body weight. No differences were observed in the anti-Xa activity in patients with and without postoperative VTE or bleeding. Substantial increase in the levels of anti-Xa activity was observed, especially in patients with renal impairment, after subcutaneous administration of FPX 2.5 mg after THA.

Topics: Age Factors; Aged; Aged, 80 and over; Anticoagulants; Arthroplasty, Replacement, Hip; Body Weight; Factor Xa; Factor Xa Inhibitors; Female; Fondaparinux; Hemorrhage; Humans; Injections, Subcutaneous; Male; Middle Aged; Polysaccharides; Prospective Studies; Time Factors; Venous Thromboembolism

The current standard initial therapies for deep venous thrombosis are low-molecular-weight heparin and unfractionated heparin. In a dose-ranging study of patients with symptomatic deep venous thrombosis, fondaparinux had efficacy and a safety profile similar to those of low-molecular-weight heparin (dalteparin).. To evaluate whether fondaparinux has efficacy and safety similar to those of enoxaparin in patients with deep venous thrombosis.. Randomized, double-blind study.. 154 centers worldwide.. 2205 patients with acute symptomatic deep venous thrombosis.. Fondaparinux, 7.5 mg (5.0 mg in patients weighing <50 kg and 10.0 mg in patients weighing >100 kg) subcutaneously once daily, or enoxaparin, 1 mg/kg of body weight, subcutaneously twice daily for at least 5 days and until vitamin K antagonists induced an international normalized ratio greater than 2.0.. The primary efficacy outcome was the 3-month incidence of symptomatic recurrent venous thromboembolic complications. The main safety outcomes were major bleeding during initial treatment and death. An independent, blinded committee adjudicated all outcomes.. 43 (3.9%) of 1098 patients randomly assigned to fondaparinux had recurrent thromboembolic events compared with 45 (4.1%) of 1107 patients randomly assigned to enoxaparin (absolute difference, -0.15 percentage point [95% CI, -1.8 to 1.5 percentage points]). Major bleeding occurred in 1.1% of patients receiving fondaparinux and 1.2% of patients receiving enoxaparin. Mortality rates were 3.8% and 3.0%, respectively.. Follow-up was incomplete in 0.4% of fondaparinux-treated patients and 1.0% of enoxaparin-treated patients.. Once-daily subcutaneous fondaparinux was at least as effective (not inferior) and safe as twice-daily, body weight-adjusted enoxaparin in the initial treatment of patients with symptomatic deep venous thrombosis.

Topics: Aged; Body Weight; Cause of Death; Double-Blind Method; Drug Administration Schedule; Enoxaparin; Female; Fibrinolytic Agents; Fondaparinux; Hemorrhage; Humans; Kidney; Male; Middle Aged; Polysaccharides; Recurrence; Treatment Outcome; Venous Thrombosis; Vitamin K

Data on the anti-Xa efficacy of fondaparinux in dialysis-dependent chronic kidney disease (DD-CKD) patients are scarce. This study characterizes the pharmacokinetics (PK) and pharmacodynamics (PD) of fondaparinux in DD-CKD patients undergoing renal replacement therapy (RRT), to assess dosing strategies.. A retrospective, observational study was conducted using data on anti-Xa activity (112 samples) from 12 (3 male and 9 female) DD-CKD patients (median (IQR) age 71 years (63-88), weight 73 kg (59-98.5)). Eleven patients underwent high-flux or low-flux hemodialysis (HD) and one patient underwent peritoneal dialysis. Three patients were also treated with therapeutic plasma exchange (TPE). A non-linear mixed effects analysis was performed using NONMEM 7.3.0.. The lab-specific slope of the relationship between fondaparinux concentration and anti-Xa levels was 1.18 IU/µg. In a one-compartment model, clearance (CL) and volume of distribution (Vd) were 0.05289 L/h and 5.55 L, respectively. High-flux HD was found to increase the CL of fondaparinux 2.26 times. TPE also considerably increased CL, but the fold-change could not be accurately estimated. Low-flux HD and peritoneal dialysis did not impact PK parameters.. Model-based simulations showed that standard dosing (2.5 mg three times weekly before HD) results in a median anti-Xa activity of 0.55 IU/mL and 0.98 IU/mL, pre- and post-low-flux HD, respectively. In patients undergoing high-flux HD, these values are approximately 27% lower. Additional caution is warranted with TPE, as this treatment can reduce anti-Xa activity even further.

Topics: Age Factors; Aged; Aged, 80 and over; Body Weight; Factor Xa Inhibitors; Female; Fondaparinux; Humans; Male; Middle Aged; Renal Insufficiency, Chronic; Renal Replacement Therapy; Retrospective Studies

Fondaparinux (FPX), a synthesized factor Xa inhibitor, is one of the most popular anticoagulants for the prevention of postoperative venous thromboembolism (VTE). Although routine monitoring is not required, the bleeding adverse events cannot be neglected, and the measurement of anti-Xa activity is expected to be monitored. The primary purpose of this study is to evaluate the performances of 2 chromogenic assays for the detection of anti-Xa activity. Furthermore, the pharmacokinetics of FPX was examined using chromogenic assays. Anti-Xa activity was measured using 2 FPX-based chromogenic substrates (S2222 and STA-Liquid Anti-Xa). The reproducibility, detection limits, linearity, and correlations between the substrates were examined using normal plasma doped with low and high concentrations of FPX formulation. In addition, anti-Xa activity in 235 clinical samples from 164 cases treated was measured, and the pharmacokinetics of FPX was evaluated. Both of the tested substrates were capable of accurately measuring the anti-Xa activity of FPX, with a lower limit of 0.05 μg/mL and a coefficient of variation of less than 10%. The repeated administration of FPX induced a gradual but significant increase in the anti-Xa activity, which was negatively correlated with body weight and estimated glomerular filtration rate. No significant correlation between the anti-Xa activity and the occurrence of postoperative VTE or bleeding event was observed. Anti-Xa activity can be successfully determined using 2 chromogenic assays and automated biochemical analyzers. The clinical significance of anti-Xa activity monitoring should be examined in the future study.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Body Weight; Chromogenic Compounds; Clinical Chemistry Tests; Dose-Response Relationship, Drug; Factor Xa Inhibitors; Female; Fondaparinux; Glomerular Filtration Rate; Hemorrhage; Humans; Male; Middle Aged; Polysaccharides; Postoperative Complications; Venous Thromboembolism

The NCCN Guidelines for Cancer-Associated Venous Thromboembolic Disease outline strategies for treatment and prevention of venous thromboembolism (VTE) in adult patients with a diagnosis of cancer or for whom cancer is clinically suspected. VTE is a common complication in patients with cancer, which places them at greater risk for morbidity and mortality. Therefore, risk-appropriate prophylaxis is an essential component for the optimal care of inpatients and outpatients with cancer. Critical to meeting this goal is ensuring that patients get the most effective medication in the correct dose. Body weight has a significant impact on blood volume and drug clearance. Because obesity is a common health problem in industrialized societies, cancer care providers are increasingly likely to treat obese patients in their practice. Obesity is a risk factor common to VTE and many cancers, and may also impact the anticoagulant dose needed for safe and effective prophylaxis. These NCCN Guidelines Insights summarize the data supporting new dosing recommendations for VTE prophylaxis in obese patients with cancer.

Topics: Adult; Anticoagulants; Body Mass Index; Body Weight; Dalteparin; Enoxaparin; Fondaparinux; Heparin; Humans; Neoplasms; Obesity; Polysaccharides; Practice Guidelines as Topic; Renal Insufficiency, Chronic; Venous Thromboembolism

Fondaparinux is a synthetic antithrombotic agent with specific anti-factor Xa activity. A population pharmacokinetic model of fondaparinux, based on data obtained in patients included in phase II/III trials, has been described. However, the validity of this model in everyday practice needed to be confirmed. This study was a multicenter, prospective cohort study in consecutive orthopaedic patients treated with 2.5 mg of fondaparinux. Anti-Xa activities were recorded in 809 patients. Population parameters and inter-individual variability were estimated using NONMEM VI software. A two-compartment model with first-order absorption best described fondaparinux pharmacokinetics. Covariates partly explaining inter-individual variability were body weight, age and creatinine clearance estimated by the simplified Modification of Diet in Renal Disease formula (MDRD). A body weight less than 50 kg and moderate renal failure increased drug exposure. Although the population pharmacokinetic model of fondaparinux was described, this one requires to be validated in everyday practice.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Anticoagulants; Body Weight; Computer Simulation; Creatinine; Factor Xa Inhibitors; Female; Fibrinolytic Agents; Fondaparinux; France; Hemorrhage; Humans; Kidney; Male; Middle Aged; Models, Biological; Nonlinear Dynamics; Orthopedic Procedures; Polysaccharides; Prospective Studies; Reproducibility of Results; Treatment Outcome; Venous Thromboembolism; Young Adult

Deep vein thrombosis (DVT) remains a major burden and fondaparinux represents a new option for DVT therapy. We sought to determine if fondaparinux offered financial advantages over low-molecular weight heparin since it is given as a fixed dose over a wide range of patient weights rather then dosed directly on weight and because fondaparinux is not associated with heparin-induced thrombocytopenia (HIT).. We conducted a cost-minimization analysis comparing fondaparinux to enoxaparin for acute anticoagulation in DVT. We modeled a cohort of 1,000 hypothetical subjects and drew estimates for model inputs from the published literature. We completed multiple sensitivity analyses to asses the significance of our assumptions and used Monte Carlo simulation to estimate the 95% confidence intervals (CIs) around our estimation of the cost differential for the two agents.. In the base case, total disease management costs per patient with fondaparinux are US 472 dollars compared to 769 dollars with enoxaparin. The 95% CI around this difference ranges from US 48 dollars to US 401 dollars. The model was mildly sensitive to the pharmacy acquisition costs of fondaparinux and enoxaparin which was the major driver of overall costs. Neither the rates of nor costs associated with DVT recurrence, major bleeding, nor HIT substantially affected our observations. Breakeven analysis indicated our findings to be robust over a wide range of likely clinical scenarios.. From the perspective of a healthcare system, fondaparinux use offers an attractive economic alternative to other agents for initial DVT therapy. Expanded reliance on fondaparinux could potentially result in savings.

Topics: Body Weight; Costs and Cost Analysis; Enoxaparin; Fondaparinux; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Models, Economic; Polysaccharides; Recurrence; Thrombosis; Venous Thrombosis

Topics: Aged; Body Weight; Cause of Death; Double-Blind Method; Drug Administration Schedule; Enoxaparin; Female; Fibrinolytic Agents; Fondaparinux; Hemorrhage; Humans; Kidney; Male; Middle Aged; Polysaccharides; Recurrence; Treatment Outcome; Venous Thrombosis; Vitamin K

Many clinicians recommend long-term, postoperative thromboprophylaxis for patients who undergo major hip or knee replacement or hip fracture surgery. However, special care must be taken when administering pharmacoprophylaxis to such patients, as they commonly exhibit characteristics that are different from those of the general population and can affect their responses to certain drugs. Among the currently available thromboprophylactic agents are warfarin, the heparins, and the recently introduced selective factor Xa inhibitor, fondaparinux. One feature of fondaparinux is that it can be administered safely and efficaciously in a wide variety of patient populations, without the need for dosage modification.

Topics: Adult; Age Factors; Aged; Anticoagulants; Antithrombins; Body Mass Index; Body Weight; Contraindications; Factor Xa Inhibitors; Female; Fondaparinux; Frail Elderly; Humans; Kidney; Liver; Male; Middle Aged; Orthopedic Procedures; Polysaccharides; Pregnancy; Racial Groups; Sex Factors; Thromboembolism