Reversal

From the Lovenox package insert :

Accidental overdosage following administration of LOVENOX (enoxaparin) may lead to hemorrhagic complications. LOVENOX should be immediately discontinued, at least temporarily, in cases of significant excess dosage. In more serious cases, protamine should be administered.

The anticoagulant effect of LOVENOX is inhibited by protamine. This effect may be largely neutralized by slow intravenous injection of protamine sulfate. However, even with higher doses of protamine, the aPTT may remain prolonged to a greater extent than usually seen with unfractionated heparin. Anti-factor Xa activity is never completely neutralized (maximum about 60%).

In the event that prompt reversal of the anticoagulant effects of enoxaparin is required at any time after LOVENOX dosing, the following table is provided as a guide for initial use of protamine. Attending physicians confronted with a potential overdosage of enoxaparin should always use their best clinical judgment in determining the appropriate dosing regimen of protamine to be administered.

Neutralization of enoxaparin by protamine

Time Since LOVENOX Dose

A second infusion of 0.5 mg protamine per 1 mg LOVENOX may be administered if the aPTT measured 2 to 4 hours after the first infusion remains prolonged.

Particular care should be taken to avoid overdosage with protamine sulfate. Administration of protamine sulfate can cause severe hypotensive and anaphylactoid reactions. Because fatal reactions, often resembling anaphylaxis, have been reported with protamine sulfate, it should be given only when resuscitation equipment and treatment of anaphylactic shock are readily available.