A1,
A2,
B,
C1,
C2,
D,
E,
F,
G-H,
I-K,
L,
M,
N,
O,
P1,
P2,
Q-R,
S,
T,
U-V,
W-Z
Xigris Warnings, Precautions, Pregnancy, Nursing, Abuse - Drotrecogin alfa
Xigris Warnings, Precautions, Pregnancy, Nursing, Abuse - Drotrecogin alfa
WARNINGS
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.
Therefore, for patients with severe sepsis who have 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 heparin (³15
units/kg/hr)
· 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.
PRECAUTIONS
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.
Immunogenicity
As with all therapeutic proteins, there is a potential for
immunogenicity. The incidence of antibody development in patients receiving
Xigris has not been adequately determined, as the assay sensitivity is inadequate
to reliably detect all potential antibody responses. One patient in the phase
2 trial developed antibodies to Xigris without clinical sequelae. One patient
in the phase 3 trial who developed antibodies to Xigris developed superficial
and deep vein thrombi during the study, and died of multi-organ failure on day
36 post-treatment but the relationship of this event to antibody is not clear.
Xigris has not been readministered to patients with severe
sepsis.
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