Weight-based dosing of enoxaparin for VTE prophylaxis in morbidly obese, medically-Ill patients

Abstract 

Introduction

In clinical trials, fixed-dose enoxaparin (40 mg once daily) reduces the risk of venous thromboembolism (VTE) in medically-ill patients. However, morbidly obese patients were under-represented in these trials and using fixed-dose enoxaparin in obese patients may be inadequate. We completed a pharmacokinetic study in morbidly obese, medically-ill patients to determine if weight-based dosing of enoxaparin for VTE prophylaxis was feasible, without excessive levels of anticoagulation, as determined by peak anti-Xa levels.

Materials and Methods

Twenty eight morbidly obese (BMI≥35 kg/m²) patients were enrolled and completed the study protocol. Enoxaparin 0.5 mg/kg was administered once daily subcutaneously and peak anti-Xa levels were measured approximately 4-6 hours after the enoxaparin dose.

Results and Conclusions

Overall, 46% of patients were female, the average age (±SD) was 54 (±11) years, and the average weight and BMI were 135.6 kg (±25.3) and 48.1 kg/m² (±11.1), respectively. The average daily dose of enoxaparin was 67 mg (±12). The average peak anti-Xa level was 0.25 (SD±0.11, range 0.08 to 0.59) units/mL. Peak anti-Xa levels did not significantly correlate with weight or BMI. There were no bleeding events, symptomatic VTE, or significant thrombocytopenia.

In morbidly obese, medically-ill patients, use of weight-based enoxaparin dosed at 0.5 mg/kg once daily is feasible and results in peak anti-Xa levels within or near recommended range for thromboprophylaxis, without any evidence of excessive anti-Xa activity. These data suggest that this weight-based regimen may be more effective than standard fixed-dose enoxaparin. Clinical outcome studies are warranted to determine the clinical safety and efficacy of this regimen.

Abbreviations: VTE, venous thromboembolism, DVT, deep vein thrombosis, PE, pulmonary embolism, LMWH, low molecular weight heparin, BMI, body mass index, FDA, federal drug administration, MDRD, modification of diet in renal disease, IRB, institutional review board, IU, international units, HIT, heparin-induced thrombocytopenia, BID, twice daily, AUC, area under the curve, ACCP, American College of Chest Physicians, CHF, congestive heart failure, OCP, oral contraceptives, ICU, intensive care unit, SD, standard deviation.

Keywords: Low-molecular weight heparin, Medically-Ill, Obesity, Pharmacokinetics, Prophylaxis, Venous Thromboembolism