Enoxaparin and Eptifibatide Coadministration
You can safely administer Lovenox (enoxaparin) while Integrilin (eptifibatide) is actively infusing—there is no need to hold or wait until after the infusion is complete. 1
Evidence Supporting Concurrent Use
The combination of enoxaparin and eptifibatide has been specifically studied and validated in high-risk acute coronary syndrome patients:
The INTERACT trial directly evaluated this combination in 746 patients with non-ST-elevation ACS, demonstrating that enoxaparin (1 mg/kg subcutaneously twice daily) plus eptifibatide (180 mcg/kg bolus followed by 2 mcg/kg/min infusion) was not only safe but actually superior to unfractionated heparin plus eptifibatide. 1
Major bleeding rates were significantly lower with the enoxaparin-eptifibatide combination (1.8%) compared to UFH-eptifibatide (4.6%, P=0.03), directly contradicting concerns about excessive bleeding risk. 1
Ischemic outcomes were markedly improved with concurrent therapy, showing reduced ischemia on continuous ECG monitoring (14.3% vs 25.4%, P=0.0002) and lower 30-day death or MI rates (5% vs 9%, P=0.031). 1
Pharmacologic Compatibility
The drugs work through complementary mechanisms without pharmacokinetic interference:
Eptifibatide pharmacokinetics remain unchanged when coadministered with enoxaparin versus UFH, with identical steady-state plasma concentrations (1610 ng/mL vs 1640 ng/mL) and no clinically significant differences in platelet aggregation inhibition or drug clearance. 2
No dose adjustments are required for either medication when used together, as enoxaparin does not affect eptifibatide's antiplatelet effects or elimination. 2
Current Guideline Recommendations
Multiple ACC/AHA guidelines explicitly endorse this combination:
The 2014 AHA/ACC NSTE-ACS guidelines recommend subcutaneous enoxaparin (1 mg/kg every 12 hours) for the duration of hospitalization or until PCI, with GP IIb/IIIa inhibitors (including eptifibatide) as a Class IIb recommendation for patients with intermediate/high-risk features. 3
The 2025 ACC/AHA ACS guidelines continue to support enoxaparin as an alternative to UFH at the time of PCI (Class 2b), with no contraindication to concurrent GP IIb/IIIa inhibitor use. 3
The 2012 ACC/AHA focused update specifically states to "discontinue anticoagulant therapy after PCI for uncomplicated cases" but makes no recommendation to hold enoxaparin during active eptifibatide infusion. 3
Critical Pitfall to Avoid
Never switch between enoxaparin and UFH in either direction once therapy is initiated, as this significantly increases bleeding risk without improving outcomes. 4, 5, 6 If you start with enoxaparin and eptifibatide, commit to this regimen rather than switching to UFH.
Practical Administration
Give enoxaparin 1 mg/kg subcutaneously every 12 hours while eptifibatide infuses at 2 mcg/kg/min (following the 180 mcg/kg bolus). 3, 1
Reduce enoxaparin to 1 mg/kg once daily if creatinine clearance is <30 mL/min. 3
Continue both agents until PCI is performed or for the duration of hospitalization (up to 8 days), then discontinue anticoagulation after uncomplicated PCI. 3