| Indication |
For the prophylaxis of deep vein thrombosis, which may lead to
pulmonary embolism, and also for the prophylaxis of ischemic
complications of unstable angina and non-Q-wave myocardial infarction,
when concurrently administered with aspirin. |
| Pharmacodynamics |
Enoxaparin is a highly acidic mucopolysaccharide formed of equal
parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic
bridges. The molecular weight ranges from 3800 to 5000 daltons.
Enoxaparin occurs in and is obtained from liver, lung, mast cells, etc.,
of vertebrates. Enoxaparin is a well known and commonly used
anticoagulant which has antithrombotic properties. Enoxaparin inhibits
reactions that lead to the clotting of blood and the formation of fibrin
clots both in vitro and in vivo. Enoxaparin acts at multiple sites in
the normal coagulation system. Small amounts of enoxaparin in
combination with antithrombin III (enoxaparin cofactor) can inhibit
thrombosis by inactivating activated Factor X and inhibiting the
conversion of prothrombin to thrombin. Once active thrombosis has
developed, larger amounts of enoxaparin can inhibit further coagulation
by inactivating thrombin and preventing the conversion of fibrinogen to
fibrin. Enoxaparin also prevents the formation of a stable fibrin clot
by inhibiting the activation of the fibrin stabilizing factor. Its use
should be avoided in patients with a creatinine clearance less than
20mL/min. In these patients, unfractionated heparin should only be used.
As for monitoring, active partial thromboplastin time (aPTT) will only
increase at high doses of low molecular weight heparins (LMWH).
Therefore, monitoring aPTT is not recommended. However, anti-Xa activity
can be measured to monitor the efficacy of the LMWH. |
| Mechanism of action |
The mechanism of action of enoxaparin is antithrombin-dependent.
It acts mainly by accelerating the rate of the neutralization of certain
activated coagulation factors by antithrombin, but other mechanisms may
also be involved. The antithrombotic effect of enoxaparin is well
correlated to the inhibition of factor Xa. Enoxaparin interacts with
Antithrombin III, Prothrombin and Factor X. Enoxaparin binds to and
accelerates the activity of antithrombin III. By activating antithrombin
III, enoxaparin preferentially potentiates the inhibition of
coagulation factors Xa and IIa. |
| Absorption |
Mean absolute bioavailability of enoxaparin, after 1.5 mg/kg given
subcutaneously, based on anti-Factor Xa activity is approximately 100%
in healthy volunteers. |
| Volume of distribution |
|
| Protein binding |
80% bound-albumin |
| Metabolism |
Undergoes desulfation and polymerization via the liver |
| Route of elimination |
Enoxaparin sodium is primarily metabolized in the liver by
desulfation and/or depolymerization to lower molecular weight species
with much reduced biological potency. Renal clearance of active
fragments represents about 10% of the administered dose and total renal
excretion of active and non-active fragments 40% of the dose. |
| Half life |
4.5 hours |
| Clearance |
Not Available |
| Toxicity |
Mouse, median lethal dose greater than 5000 mg/kg. Another side
effect is heparin induced thrombocytopenia (HIT syndrome). HIT is caused
by an immunological reaction that makes platelets form clots within the
blood vessels, thereby using up coagulation factors. |
