Bleeding is the most common serious adverse effect associated with Xigris therapy. Each
patient being considered for therapy with Xigris should be carefully evaluated and anticipated
benefits weighed against potential risks associated with therapy.
Certain conditions, many of which led to exclusion from the Phase 3 trial, are likely to increase
the risk of bleeding with Xigris therapy. For individuals with one or more of the following
conditions, the increased risk of bleeding should be carefully considered when deciding whether
to use Xigris therapy:
• Concurrent therapeutic dosing of heparin to treat an active thrombotic or embolic event
• Platelet count <30,000 x 106/L, even if the platelet count is increased after transfusions
• Prothrombin time-INR >3.0
• Recent (within 6 weeks) gastrointestinal bleeding
• Recent administration (within 3 days) of thrombolytic therapy
• Recent administration (within 7 days) of oral anticoagulants or glycoprotein IIb/IIIa inhibitors
• Recent administration (within 7 days) of aspirin >650 mg per day or other platelet inhibitors
• Recent (within 3 months) ischemic stroke (see CONTRAINDICATIONS)
• Intracranial arteriovenous malformation or aneurysm
• Known bleeding diathesis
• Chronic severe hepatic disease
• Any other condition in which bleeding constitutes a significant hazard or would be
particularly difficult to manage because of its location
Should clinically important bleeding occur, immediately stop the infusion of Xigris. Continued
use of other agents affecting the coagulation system should be carefully assessed. Once adequate
hemostasis has been achieved, continued use of Xigris may be reconsidered.
Xigris should be discontinued 2 hours prior to undergoing an invasive surgical procedure or
procedures with an inherent risk of bleeding. Once adequate hemostasis has been achieved,
initiation of Xigris may be reconsidered 12 hours after major invasive procedures or surgery or
restarted immediately after uncomplicated less invasive procedures.
Laboratory Tests
Most patients with severe sepsis have a coagulopathy that is commonly associated with
prolongation of the activated partial thromboplastin time (APTT) and the prothrombin time (PT).
Xigris may variably prolong the APTT. Therefore, the APTT cannot be reliably used to assess
the status of the coagulopathy during Xigris infusion. Xigris has minimal effect on the PT and the
PT can be used to monitor the status of the coagulopathy in these patients.
