Accidental overdosage following administration of FRAGMIN may lead to hemorrhagic complications. FRAGMIN 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 FRAGMIN is inhibited by protamine. This effect may be largely neutralized by slow intravenous injection of protamine sulphate. The dose of protamine to be given should be 1 mg protamine per 100 anti-Xa IU of FRAGMIN administered. A second infusion of 0.5 mg protamine per 100 anti-Xa IU of FRAGMIN may be administered if the APTT measured 2 to 4 hours after the first infusion remains prolonged. However, even with higher doses of protamine, the APTT may remain prolonged to a greater extent than usually seen with unfractionated heparin. Anti-Xa activity is never completely neutralized (maximum about 60%).
Particular care should be taken to avoid overdosage with protamine sulphate. Administration of protamine sulphate can cause severe hypotensive and anaphylactoid reactions. Because fatal reactions, often resembling anaphylaxis, have been reported with protamine sulphate, it should be given only when resuscitation equipment and treatment of anaphylactic shock are readily available. Refer to the protamine sulphate Product Monograph for further directions for use.