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
Refludan Warnings, Precautions, Pregnancy, Nursing, Abuse - Lepirudin
Refludan Warnings, Precautions, Pregnancy, Nursing, Abuse - Lepirudin
WARNINGS
Hemorrhagic Events
As with other anticoagulants, hemorrhage can occur at any site
in patients receiving REFLUDAN. An unexpected fall in hemoglobin, fall in blood
pressure or any unexplained symptom should lead to consideration of a hemorrhagic
event. While patients are being anticoagulated with REFLUDAN, the anticoagulation
status should be monitored closely using an appropriate measure such as the
aPTT (See ADVERSE REACTIONS and DOSAGE
AND ADMINISTRATION: Monitoring Section). Intracranial bleeding following
concomitant thrombolytic therapy with rt-PA or streptokinase may be lifethreatening.
There have been reports of intracranial bleeding with REFLUDAN in the absence
of concomitant thrombolytic therapy (see ADVERSE
REACTIONS).
For patients with increased risk of bleeding, a careful assessment
weighing the risk of REFLUDAN administration vs its anticipated benefit has
to be made by the treating physician.
In particular, this includes the following conditions:
Recent puncture of large vessels or organ biopsy
Anomaly of vessels or organs
Recent cerebrovascular accident, stroke, intracerebral surgery, or other
neuraxial procedures
Severe uncontrolled hypertension
Bacterial endocarditis
Advanced renal impairment (see also WARNINGS:
Renal Impairment)
Hemorrhagic diathesis
Recent major surgery
Recent major bleeding (eg, intracranial, gastrointestinal, intraocular,
or pulmonary bleeding)
Recent active peptic ulcer
Renal Impairment
With renal impairment, relative overdose might occur even with
standard dosage regimen. Therefore, the bolus dose and the rate of patients
infusion must be reduced in patients with known or suspected renal insufficiency
(see CLINICAL PHARMACOLOGY: Pharmacokinetic
Properties and DOSAGE AND ADMINISTRATION:
Monitoring and Adjusting Therapy; Use in Renal Impairment).
PRECAUTIONS
General
Antibodies. Formation of antihirudin antibodies was
observed in about 40% of HIT patients treated with REFLUDAN. This may increase
the anticoagulant effect of REFLUDAN possibly due to delayed renal elimination
of active lepirudin-antihirudin complexes (see also PRECAUTIONS:
Animal Pharmacology and Toxicology). Therefore, strict monitoring of aPTT is
necessary also during prolonged therapy (see also PRECAUTIONS:
Laboratory Tests and DOSAGE AND ADMINISTRATION:
Monitoring and Adjusting Therapy; Standard Recommendations). No evidence of
neutralization of REFLUDAN or of allergic reactions associated with positive
antibody test results was found.
Liver Injury. Serious liver injury (eg, liver cirrhosis)
may enhance the anticoagulant effect of REFLUDAN due to coagulation defects
secondary to reduced generation of vitamin K-dependent coagulation factors.
Reexposure. During the HAT-1 and HAT-2 studies, a total
of 13 patients were reexposed to REFLUDAN. One of these patients experienced
a mild allergic skin reaction during the second treatment cycle. In post marketing
experience, anaphylaxis after reexposure has been reported. (see PRECAUTIONS
Allergic Reactionsbelow and ADVERSE REACTIONS
Adverse Events from Post Marketing Reports.)
Allergic Reactions. There have been reports of allergic
and hypersensitivity reactions including anaphylactic reactions. Serious anaphylactic
reactions that have resulted in shock or death have been reported. These reactions
have been reported during initial administration or upon second or subsequent
reexposure(s).
Laboratory Tests
In general, the dosage (infusion rate) should be adjusted according
to the aPTT ratio (patient aPTT at a given time over an aPTT reference value,
usually median of the laboratory normal range for aPTT); for full information,
see DOSAGE AND ADMINISTRATION: Monitoring
and Adjusting Therapy; Standard Recommendations. Other thrombin-dependent coagulation
assays are changed by REFLUDAN (see also DESCRIPTION).
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