Enoxaparin dosing

In all these trials, enoxaparin was administered at the dose of I mg/kg SC every 12 hours, in order to achieve therapeutic anti-Xa levels, This is of importance as it has been demonstrated that low anti-Xa activity (<0.5 lU/mL) was an independent predictor of poor outcome among ACS patients conversely, anti-Xa activity, within the target range of 0.5 to 1.2lU/mL, is not related to bleeding events (23), Among patients with impaired creatinine clearance (chronic kidney disease in elderly patients), the therapeutic range is achieved safely by reducing enoxaparin dose (24),... 

FIGURE 16 Changes in anti-factor Xa activity after nasal administration of enoxaparin formulated in saline or in presence of different concentrations of the following (a) octanoyl-sucrose (b) decanoylsucrose (c) dodecanoylsucrose (d) sodium glycocholate and dodecanoyl-sucrose to anesthetized rats (enoxaparin dose, 330U/kg). Data represent mean + SEM, n = 3,5. (Reproduced from ref. 84 with permission of Pharmaceutical Press.)... 

On the other hand, the maximum tolerated dose of enoxaparin, a low-molecular-weight heparin, during vitrectomy for rhegmatogenous retinal detachment with proliferative vitreoretinopathy and severe diabetic retinopathy was determined (103). The study was able to achieve the 6.0 lU/ml maximum dose in the infusion fluid, and enoxaparin dose escalation did not result in a dose-dependent increase in acute side effects. 

Dose may depend on the lapsed time after LMWH administration (e.g., 0.5 mg protamine per 1 mg enoxaparin to a maximum of 50 mg if greater than 8 h has passed since the last administered dose)... 

Prior to initiating treatment with a LMWH, baseline laboratory tests should include PT (prothrombin time)/INR, aPTT, complete blood cell count (CBC), and serum creatinine. Monitor the CBC every 3 to 4 days during the first 2 weeks of therapy, and every 2 to 4 weeks with extended use.5 Use LMWHs cautiously in patients with renal impairment. Specific dosing recommendations for patients with a creatinine clearance (CrCl) less than 30 mL/minute are currently available for enoxaparin but lacking for other agents of the class (Table 7-3). Current guidelines recommend the use of UFH over LMWH in patients with severe renal dysfunction (CrCl less than 30 mL/minute).8... 

VTE in pediatric patients. Children less than 1 year old require higher doses (e.g., enoxaparin 1.5 mg/kg SC every 12 hours). Monitor anti-factor Xa activity to guide dosing in children.32... 

Benzyl alcohol The multiple-dose vials of dalteparin, enoxaparin, and tinzaparin contain benzyl alcohol as a preservative. Benzyl alcohol has been associated with a fatal gasping syndrome in premature infants. Because benzyl alcohol may cross the placenta, do not use LMWHs preserved with benzyl alcohol in pregnant women. Thromboembolic events If thromboembolic events occur despite LMWH prophylaxis, discontinue and initiate appropriate therapy. 

Mechanical prosthetic heart valves The use of enoxaparin injection has not been adequately studied for thromboprophylaxis or long-term use in patients with mechanical prosthetic heart valves. Isolated cases of prosthetic heart valve thrombosis have been reported in patients with mechanical prosthetic heart valves who have received enoxaparin for thromboprophylaxis. Some of these cases were pregnant women in whom thrombosis led to maternal and fetal deaths. Frequent monitoring of peak and trough anti-Factor Xa levels and dose adjustment may be needed. 

Overdose may lead to bleeding complications ranging from local ecchymoses to major hemorrhage. Antidote Protamine sulfate (1% solution) equal to the dose of enoxaparin injected. One mgprotamine sulfate neutralizes 1 mg enoxaparin, A second dose of 0,5 mg protamine sulfate per 1 mg enoxaparin may be given if aPTT tested 2-4 hr after first injection remains prolonged. 

Prophylactic enoxaparin is given subcutaneously in a dosage of 30 mg twice daily or 40 mg once daily. Full-dose enoxaparin therapy is 1 mg/kg subcutaneously every 12 hours. This corresponds to a therapeutic anti-factor Xa level of 0.5—1 unit/mL. Selected patients may be treated with enoxaparin 1.5 mg/kg once a day, with a target anti-Xa level of 1.5 units/mL. The prophylactic dose of dalteparin is 5000 units subcutaneously once a day therapeutic dosing is 200 units/kg once a day for venous disease or 120 units/kg every 12 hours for acute coronary syndrome. The use of LMW heparins is discouraged or contraindicated in patients with renal insufficiency or body weight greater than 150 kg. 

Efficacy and safety oftenecteplase in combination with enoxaparin, abciximab, or unfractionated heparin the ASSENT-3 randomized trial in acute myocardial infarction. Lancet 2001 358 605. LincoffAM, Califf RM, Van De WerfE etal. Mortality at I year with combination platelet glycoprotein llb/llla inhibition and reduced-dose fibrinolytic therapy vs conventional fibrinolytic therapy for acute myocardial infarction GUSTO V randomized trial. JAMA 2002 288 2130. 

In a preliminary study, Choussat et al. (7) included 242 consecutive patients to receive a single intravascular (IV) bolus of enoxaparin (0.5 mg/kg) during elective PCI. A peak anti-Xa of >0.5 lU/mL was obtained in 97.5% of the population (Fig. 2) this dose allowed immediate sheath removal when used alone and did not require dose adjustment when used with a glycoprotein (GP) llb-llla inhibitor. 

Distribution of anti-Xa activity levels at the beginning (A) and end (B) of percutaneous coronary intervention after a single intravascular dose of enoxaparin 0.5 mg/kg. Source From Ref. 7. 

Converse to UFH, the use of enoxaparin during PCI did not require anticoagulation monitoring, and there was no dose modification with concomitant GP llb-llla receptor blockers administration (9). 

In the NICE-3 study (14), 661 ACS patients were treated with enoxaparin SC I mg/kg plus abciximab, eptifibatide, or tirofiban at standard doses. Two strategies were combined for the transition from the ward to the catheter laboratory no interruption and no addition of enoxaparin for PCI within eight hours of the last SC injection and an additive IV bolus of 0.3 mg/kg when PCI was performed between 8 and 12 hours of the last SC injection. The major bleeding rate was 4.5% and the in-hospital death/MI/urgent target vessel revascularization rate was 5.7%. 

LMWH is a safe and efficient alternative to UFH during PCI. From a practical point of view, a unique IV dose of 0.5 mg/kg enoxaparin is convenient, simple, and does not need adjustment for Mb—Ilia antagonist use nor for renal function. In addition, this unique dose requires no anticoagulant monitoring and allows an early sheath removal. 

Choussat R, Montalescot G, Collet JR et al. A unique, low dose of intravenous enoxaparin in elective percutaneous coronary intervention, J Am Coll Cardiol 2002 40 1943-1 950. 

Collignon R Frydman A, Caplain H, et al. Comparison of the pharmacokinetic profiles of three low-molecular mass heparins -dalteparin, enoxaparin and nadroparin administered subcutaneously in healthy volunteers (doses for prevention of thromboembolism). Thromb Haemost 1995 73 630-640. 

A 41-year-old woman, with liver lacerations, rib fractures, and pneumothorax after a motor vehicle accident, was given haloperidol for agitation on day 7. During the first 24 hours she received a cumulative intravenous dose of 15 mg, 70 mg on day 2, 190 mg on day 3,160 mg on days 4 and 5, and 320 mg on day 6. An hour after the first dose of 80 mg on day 7, she had ventricular extra beats followed by 5-beat and 22-beat runs of ventricular tachycardia. The rhythm strips were consistent with polymorphous ventricular tachycardia or torsade de pointes and the QTC interval was 610 ms (normally under 450 in women). She received intravenous magnesium sulfate 2 g. Concurrent medications included enoxaparin, famotidine, magnesium hydroxide, ampicillin/sulbactam, nystatin suspension, midazolam, and 0.45% saline with 20 mmol/1 of potassium chloride. She had no further dysrhythmias after haloperidol was withdrawn. Eight days after the episode of torsade de pointes she had a QTC interval of 426 ms. 

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