What is the recommended dose of Lovenox (enoxaparin) for an adult patient with a history of fluctuating International Normalized Ratio (INR) on Coumadin (warfarin)?

Lovenox Dosing for Bridging Anticoagulation in Fluctuating INR

For an adult patient with fluctuating INR on warfarin requiring bridging with enoxaparin, administer 1 mg/kg subcutaneously every 12 hours (or 1.5 mg/kg once daily) until the INR stabilizes in the therapeutic range for 2 consecutive days. 1

Standard Dosing Regimen

The therapeutic dose of enoxaparin for bridging anticoagulation follows two acceptable protocols 1:

• Twice-daily dosing: 1 mg/kg subcutaneously every 12 hours
• Once-daily dosing: 1.5 mg/kg subcutaneously once daily

Both regimens are equally effective for maintaining anticoagulation while warfarin is being adjusted or temporarily held 1, 2. The twice-daily regimen provides more consistent anticoagulation levels throughout the day, while once-daily dosing offers greater convenience for outpatient management 2.

Overlap Strategy with Warfarin

Continue enoxaparin alongside warfarin for a minimum of 5-7 days and until the INR reaches therapeutic range (2.0-3.0) for 2 consecutive days 1. This overlap is critical because:

• Warfarin takes 5-7 days to achieve full anticoagulant effect 1
• Early INR elevation reflects depletion of factor VII (short half-life) but does not indicate adequate anticoagulation of factors II, IX, and X 1
• Premature discontinuation of enoxaparin leaves patients unprotected during the warfarin initiation period 1

Dose Adjustments for Special Populations

Elderly Patients (≥75 years)

For patients 75 years and older, reduce the dose to 0.75 mg/kg subcutaneously every 12 hours (no initial bolus if used in acute settings) 3. Elderly patients have increased bleeding risk and altered pharmacokinetics requiring dose reduction 3.

Renal Impairment

For creatinine clearance <30 mL/min, reduce dose to 1 mg/kg once every 24 hours 1. Enoxaparin is renally cleared, and accumulation occurs in severe renal dysfunction, significantly increasing bleeding risk 1.

Obesity

For patients weighing >120 kg, the optimal dose remains unclear, but standard weight-based dosing (1 mg/kg every 12 hours) is typically used with close monitoring 1.

Monitoring Requirements

• No routine anti-Xa monitoring is required for standard therapeutic dosing in most patients 1
• Consider anti-Xa level monitoring (target 0.5-1.0 U/mL for twice-daily dosing, 1.0-2.0 U/mL for once-daily dosing) in patients with renal impairment, obesity, or pregnancy 1
• Check INR every 2-4 days during the overlap period until stable in therapeutic range 4
• Monitor for signs of bleeding (hemoglobin, hematocrit) especially in high-risk patients 1

Critical Pitfalls to Avoid

Never use enoxaparin for thromboprophylaxis in patients with mechanical prosthetic heart valves 1. The FDA and manufacturer strengthened warnings against this practice due to increased risk of valve thrombosis and thromboembolic events 1.

Do not discontinue enoxaparin based solely on a single therapeutic INR value 1. The INR must be therapeutic for at least 2 consecutive days to ensure adequate warfarin effect 1.

Avoid administering enoxaparin within 10-12 hours before neuraxial anesthesia or epidural catheter removal 1. After catheter removal, wait at least 2 hours before administering the next enoxaparin dose to minimize spinal hematoma risk 1.

Addressing the Underlying Problem

While bridging with enoxaparin, identify and correct the cause of INR fluctuation 5, 4:

• Review all medications for drug interactions (antibiotics, antifungals, amiodarone, NSAIDs)
• Assess dietary vitamin K intake changes
• Evaluate for intercurrent illness affecting warfarin metabolism
• Check liver and renal function
• Assess medication adherence and understanding

Once the cause is identified and corrected, resume warfarin at a reduced weekly dose (typically 10-20% reduction from previous maintenance dose) to prevent recurrence 6, 4.

Duration of Therapy

Continue enoxaparin bridging until 1:

• INR is stable in therapeutic range (2.0-3.0) for 2 consecutive days
• The underlying cause of INR fluctuation is identified and corrected
• The patient demonstrates reliable warfarin dosing and monitoring compliance

For most patients with simple INR fluctuation, this requires 5-10 days of enoxaparin therapy 1.