Enoxaparin (Lovenox)

Enoxaparin, a low molecular weight heparin that is renally cleared, is not recommended for use in dialysis patients because of increased risk of bleeding complications.

Acts at multiple sites in the normal coagulation system.

Small amounts of enoxaparin in combination with antithrombin III and can inhibit thrombosis by inactivating activated Factor X and inhibiting the conversion of prothrombin to thrombin.

Once active thrombosis has developed, larger amounts of enoxaparin can inhibit further coagulation by inactivating thrombin and preventing the conversion of fibrinogen to fibriin.

Also prevents the formation of a stable fibrin clot by inhibiting the activation of the fibrin stabilizing factor.

Has 110 anti-Xa units per milligram.

Treatment Dose with normal renal function 1 mg/kg/dose q 12 h or 1.5 mg/kg/dose q 24 h in DVT patients only and with Cr CL < 30 ml/min 1 mg/kg/dose q 24 h or (0.5 mg/kg/dose q12hrs)

Prophylactic Dose 0.5 mg/kg/dose or 40 mg daily.

Maximum dose is 2.0 mg/kg/dose BID.

Monitoring of Low Molecular Weight Heparin in Renal Failure and Obese and Underweight patients:

On day 2, Anti-Factor Xa should be drawn 4 hours after the SQ administration of Enoxaparin. If therapeutic, a weekly check on the Anti-Factor Xa level is sufficient.

The therapeutic anti-Xa level for treatment dose therapy is 0.7-1.1 units/mL.

The target anti Xa level for prophylactic dose therapy is 0.2-0.3 units/mL.

For patients on long term Enoxaparin therapy (> 3 months), consider bone densitometry studies at baseline and then every 6 months to assess for possible osteoporosis.

Enoxaparin may accumulate in the body over time and therefore adjust dosing requirements.

With normal renal function the usual dose is 1 mg per kilogram to 12 hours or 1.5 mg per kilogram Q. 24 hours.

With creatinine clearance of less than 30 mL per minute per dose is 1 mg per kilogram to 24 hours.

There is a relationship between levels of low molecular weight (LMW) heparin and both bleeding and inhibition of thrombosis.

Recommendation is for decreasing daily dose by one half with severe renal impairment of less than creatinine clearance 30 mL/min.

In 163 patients undergoing total hip replacement who were given prophylaxis once daily with a LMW heparin, lovenox: Fifty patients received 60 mg of enoxaparin and 113 received 40 mg, both regimens being administered subcutaneously once daily. Blood samples for anti-factor Xa levels were collected 12 hours after the injection on the day of surgery and on days 1, 3 and 6, postoperatively. The incidence of wound hematoma was 5.3% when the maximum anti-factor Xa level was less than or equal to 0.2 units per ml, but increased to 24.5% when the anti-factor Xa level exceeded 0.2 units per ml (Levine MN et al).

The incidence of postoperative thrombosis was low (6.3%) if the minimum anti-factor Xa level exceeded 0.1 units per ml, but increased to 14.6% when less than or equal to 0.1 units per ml, and to 18.8% if the anti-factor Xa findings suggest that when enoxaparin is administered as a once daily subcutaneous injection, the 12 hour anti-factor Xa level should not exceed 0.2 units per ml to minimize bleeding and levels greater than 0.05 units per ml should be obtained to optimize efficacy (Levine MN et al).

In a study reviewing bleeding complications in patients who receive enoxaparin sodium at current recommendations and have moderate renal impairment of creatinine clearance of 30 to 50 mL per minute with patients receiving the same dose but normal renal function with a creatinine clearance of greater than 80 mL minute: primary endpoint was clinically relevant major bleeding resulting in death, prolonged or initial hospitalization, or emergency department visit-One of every five patients with compromised renal function developed bleeding complications versus one of 20 patients with normal renal function (DeCarolis DD et al).

For prophylactic use the dose is 0.5 mg per kilogram or 40 mg a day.

Maximum dose 2 mg per kilogram BID.

Monitoring obese and patients with reNal insufficiency: it is suggested that on day two a blood sample should be drawn four hours after the subcutaneous administration of this drug to check anti-factor Xa levels.

Treatment Nomogram for enoxaparin treatment:

Anti-factor Xa level less than .35 units per milliliter-increase the dose by 25%.

Anti-factor Xa level 0.35-0.69 units by milliliter-increase the dose by 15%.

Anti-factor Xa level 0.7-1.1 units per milliliter-same dose.

Anti-factor Xa leve 1.1-1.5 units per milliliter-decrease dose by 20%.

Anti-factor Xa level 1.6-2.0 units per milliliter-decrease dose by 30%.

Anti-factor Xa level greater than two units per milliliter-doses should be held and subsequent re-checking of anti-factor Xa levels still the level is less than 0.5 units per milliliter.

Protamine sulfate in equimolar concentrations can neutralize the anti-factor IIa activity but results in only partial neutralization of anti-factor Xa activity.

If protamine is given within 3 to 4 hours of enoxaparin the intravenous dose of protamine is 1 mg per 1 mg of enoxaparin given in the last dose: a half dose should be considered in six hours since the half-life of enoxaparin is longer than that of protamine.

40 mg subcutaneously daily prophylactic dose.

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