Home » Drug Information » FDA Approved Drugs » 2000
Medical Areas: Cardiology/Vascular Diseases | Hematology
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The following drug information is obtained from various newswires, published
medical journal articles, and medical conference presentations.
Company: Texas Biotechnology Corporation, SmithKline Beecham
Approval Status: Approved June 2000
Treatment Area: Heparin-induced thrombocytopenia and thrombosis syndrome
Heparin is the most commonly used anticoagulant for patients
requiring immediate anticoagulation therapy. Heparin-induced
thrombocytopenia (HIT) has an immunologic basis and is commonly
associated with venous thrombosis. The availability of direct
thrombin inhibitors has assisted physicians in managing this
HIT is an immunoglobulin-mediated adverse drug reaction that is
characterized by platelet activation, thrombocytopenia, and a high
risk of thrombotic complications among patients receiving or who
have recently received heparin. HIT is one of the most important
immunologic drug reactions.
Thrombocytopenia is usually mild to moderate, with platelet
counts ranging from 20 to 150 x 109/L. Similarly, a fall in
platelet count of 50% or more that begins later than 5 days after
the start of heparin therapy, but with the platelet count still
above the usual threshold for thrombocytopenia (150 x 109/L),
should also raise the suspicion of HIT.13 By comparison,
thrombocytopenia induced by sulfa drugs and quinine is typically
much more severe. (from uspharmacist.com)
The conclusion that Argatroban is an effective treatment for
heparin-induced thrombocytopenia (HIT) and heparin-induced
thrombocytopenia and thrombosis syndrome (HITTS) is based upon the
data from a historically controlled efficacy and safety study
(Study 1) and a follow-on efficacy and safety study (Study 2).
These studies were comparable with regard to study design, study
objectives, dosing regimens as well as study outline, conduct, and
In these studies, 568 adult patients were treated with
Argatroban and 193 adult patients made up the historical control
group. Patients were required to have a clinical diagnosis of
heparin-induced thrombocytopenia, either without thrombosis (HIT)
or with thrombosis (HITTS) and be males or non-pregnant females
between the age of 18 and 80 years old.
Patients with documented unexplained aPTT greater than 200% of
control at baseline, documented coagulation disorder or bleeding
diathesis unrelated to HITTS, a lumbar puncture within the past 7
days or a history of previous aneurysm, hemorrhagic stroke, or
recent thrombotic stroke, within the past 6 months, unrelated to
HITTS were excluded from these studies.
The primary efficacy analysis was based on a comparison of event
rates for a composite endpoint that included death (all causes),
amputation (all causes) or new thrombosis during the treatment and
follow-up period (study days 0 to 37). Secondary analyses included
evaluation of the event rates for the components of the composite
endpoint as well as time-to-event analyses.
A categorical analysis showed a significant improvement in the
composite outcome in patients with HIT and HITTS treated with
Argatroban versus those in the historical control group.
Side effects may include:
- Cardiac Arrest
- Ventricular tachycardia
- Urinary tract infection
- Atrial fibrillation
- Abnormal renal function
- Abdominal pain
- Cerebrovascular disorder
There were hemorrhagic events of both minor and major status in
the following areas:
- Genitourinary and hematuria
- Decrease hemoglobin/hematocrit
- Multisystem hemorrhage and DIC
- Limb and BKA stump
- Genitourinary and hematuria
- Decrease in hemoglobin and hematocrit
Mechanism of Action
Argatroban is a direct thrombin inhibitor that reversibly binds
to the thrombin active site. It does not require the co-factor
antithrombin III for antithrombotic activity. Argatroban exerts its
anticoagulant effects by inhibiting thrombin-catalyzed or induced
reactions, including fibrin formation; activation of coagulation
factors V, VIII, and XIII; protein C; and platelet aggregation.
Argatroban is highly selective for thrombin with an inhibitory
constant of 0.04 uM. At therapeutic concentrations, argatroban has
little or no effect on related serine proteases.
Argatroban is capable of inhibiting the action of both free and
clot-associated thrombin. It does not interact with heparin-induced
antibodies. (from fda.gov)
It is not known whether this drug is excreted in human milk.
Because many drugs are, and because of the potential for
nursing-infant harm, a decision should be made whether to
discontinue nursing or discontinue the drug.