| Indication |
Approved for: (1) prophylaxis of VTE for up to one month post
surgery in patients undergoing orthopedic surgery of the lower limbs
such as hip fracture, hip replacement and knee surgery; (2) prophylaxis
of VTE patients undergoing abdominal surgery who are at high risk of
thromboembolic complications (e.g. patients undergoing abdominal cancer
surgery); (3) treatment of acute DVT and PE; (4) management of UA and
NSTEMI for the prevention of death and subsequent myocardial infarction
(MI); and (5) management of STEMI for the prevention of death and
myocardial reinfarction in patients who are managed with thrombolytics
or who are initially to receive no form of reperfusion therapy.
Fondaparinux should not be used as the sole anticoagulant during
percutaneous coronary intervention (PCI) due to an increased risk of
guiding catheter thrombosis. |
| Pharmacodynamics |
Fondaparinux binds specifically to the natural anticoagulant
factor, ATIII. Binding to ATIII potentiates the neutralizing action of
ATIII on Factor Xa 300-times. Neutralization of Factor Xa decreases the
conversion of prothrombin to thrombin, which subsequently decreases the
conversion of fibrinogen to fibrin (loose meshwork). The decrease in
thrombin also decreases the activation of Factor XIII, which decreases
the conversion of fibrin in its loose meshwork form to its stabilized
meshwork form. Disruption of the coagulation cascade effectively
decreases the formation of blood clots. Fondaparinux does not inactivate
thrombin (activated Factor II). According to the manufacturer,
fondaparinux has no known effect on platelet function. In studies
comparing fondaparinux to enoxaparin, decreases in platelet levels were
observed in similar numbers of patients from both groups (2-5%) (PMID
11794148, 12049860). At the recommended dose, Fondaparinux does not
affect fibrinolytic activity or bleeding time. There is no antidote for
fondaparinux. Monitoring of the anticoagulant activity of fondaparinux
is not generally required. The anti-factor Xa assay may be used to
monitor therapy in special populations such as those with renal
impairment or who are pregnant. Complete blood count (CBC) and kidney
function should be monitored during treatment. |
| Mechanism of action |
The antithrombotic activity of fondaparinux is the result of
ATIII-mediated selective inhibition of Factor Xa. By selectively binding
to ATIII, Fondaparinux potentiates (about 300 times) the neutralization
of Factor Xa by ATIII. Neutralization of Factor Xa interrupts the blood
coagulation cascade and thus inhibits thrombin formation and thrombus
development. It is thought that fondaparinux is unlikely to induce
thrombocytopenia via a heparin-induced thrombocytopenia (HIT)-like
mechanism given its chemical structure (PMID 19825921). As a result,
fondaparinux has been used as an alternative anticoagulant in
heparin-induced thrombocytopenia (HIT) patients (PMID 19737996,
19432027, 18217156). However, it is important to note that rare cases of
HIT have been reported in patients treated with fondaparinux (PMID
20351685, 20351686). |
| Absorption |
100% bioavailability when administered subcutaneously |
| Volume of distribution |
- 7 – 11 L (healthy adults), distributed primarily in blood
|
| Protein binding |
94% in vitro protein binding specifically to ATIII |
| Metabolism |
Not metabolized |
| Route of elimination |
In individuals with normal kidney function, fondaparinux is eliminated in urine mainly as unchanged drug. |
| Half life |
17-21 hours |
| Clearance |
Not Available |
| Toxicity |
As with other anticoagulants, the main concern is increased bleed
risk. The risk of hemorrhage may increase with decreased renal function,
body mass less than 50 kg, and moderate to severe hepatic function. |
