Fondaparinux dosing

Fondaparinux has been used for the treatment of DVT and PE in two large Phase III trials and is approved by the FDA for these indications. Fondaparinux is as safe and effective as IV UFH for the treatment of PE and SC LMWH for DVT treatment.36,40 The recommended dose for fondaparinux in the treatment of VTE is based on the patient s weight (Table 7-3). Fondaparinux is renally eliminated and accumulation can occur in patients with renal dysfunction. Due to the lack of specific dosing guidelines, fondaparinux is contraindicated in patients with severe renal impairment (CrCl less than 30 mL/minute). Baseline renal function should be measured and monitored closely during the course... 

Initiate unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH) or fondaparinux by injection (see Table 7-3 for dosing guidelines)... 

If the patient is to be treated at home, dispense to the patient a 5- to 7-day supply of prefilled LMWH or fondaparinux syringes in patient-specific dose. 

If the patient is being treated with UFH, remeasure aPTT (or anti-factor Xa activity), and adjust dose if necessary. If patient is being treated with LMWH or fondaparinux, continue therapy. 

Hold or adjust warfarin dose as necessary. Discontinue UFH, LMWH, or fondaparinux if INR is greater than 2 on two consecutive occasions. If the patient requires continued treatment with UFH, measure aPTT, and adjust dose if necessary. 

Adjust warfarin dose as necessary. Consider restarting LMWH or fondaparinux if INR drops below 1.5. 

DVT prophylaxis In patients undergoing hip fracture surgery, hip replacement surgery, or knee replacement surgery, the recommended dose is 2.5 mg subcutaneously once daily. After hemostasis has been established, give the initial dose 6 to 8 hours after surgery. The usual duration of administration is 5 to 9 days. Admixture incompatibilities Do not mix fondaparinux with other injections or infusions. 

Elderly The risk of fondaparinux-associated major bleeding increased with age. Careful attention to dosing directions and concomitant medications (especially antiplatelet medication) is advised. 

Primary prevention of venous thrombosis reduces the incidence of and mortality rate from pulmonary emboli. Heparin and warfarin may be used to prevent venous thrombosis. Subcutaneous administration of low-dose unfractionated heparin, low-molecular-weight heparin, or fondaparinux provides effective prophylaxis. Warfarin is also effective but requires laboratory monitoring of the prothrombin time. 

Fondaparinux Urgent and elective PCI (53) Optimal dosing still being determined Similar efficacy and safety to UFH (53)... 

Indications. Heparin is used for the prophylaxis and therapy of thrombosis. For the former, low dosages, given subcutaneously, are suf cient. Unfractionated heparin must be injected about three time daily, fractionated heparins and fondaparinux can be administered once daily. For treatment of thrombosis, heparin must be infused intravenously in an increased daily dose. 

In healthy volunteers, steady-state fondaparinux did not alter the pharmacodynamic effects of a single dose of piroxicam 20 mg (23). Piroxicam did not alter the pharmacokinetics of fondaparinux. 

The primary adverse effect associated with fondaparinux therapy is bleeding." " The rate of major bleeding in the VTE prophylaxis trials was approximately 2% to 3%. The risk of major bleeding appears to be related to weight therefore, in patients who weigh less than 50 kg, fondaparinux is contraindicated for VTE prophylaxis, and the treatment dose is only 5 mg every 24 hours. Similar to UFH and the LMWHs, fondaparinux should be used with extreme caution in patients with neuraxial anesthesia or following a spinal puncture owing to the risk for spinal or epidural hematoma formation. Unlike UFH and the LMWHs, fondaparinux does not cause heparin-induced thrombocytopenia and does not produce cross-sensitivity in vitro." A specific antidote to reverse the antithrombotic activity of fondaparinux is not currently available, but several potential products have been evaluated. 

The most extensively studied agents for the prevention of VTE are UEH, the LMWHs, and fondaparinux. The LMWHs and fon-daparinux provide superior protection against VTE compared with low-dose Their more predictable absorption when given by... 

Acute anticoagulation Acute treatment of DVT or PE should be with LMWH, fondaparinux, intravenous UFH, or adjusted-dose subcutaneous UFH. 1A... 

Fondaparinux has been shown in two recent cUnical trials to be a safe and effective alternative to enoxaparin and intravenous UFEf for the treatment of VTE (see Table 19-17). In the MATISSE DVT trial, a fixed-dose regimen of fondaparinux (7.5 mg/day) given by subcutaneous injection was compared with the standard weight-adjusted dosing of enoxaparin (1 mg/kg every 12 hours) for the acute treatment of DVT followed by 3 months of warfarin therapy. In the MATISSE PE trial, fondaparinux (7.5 mg subcutaneously every 24 hours) was compared with UFH administered by intravenous infusion. In both trials, the dose of fondaparinux was increased to 10 mg subcutaneously every 24 hours for patients who weighed more than 100 kg and reduced to 5 mg every 24 hours for those who weighed less than 50 kg. Fondaparinux received FDA approval for the acute treatment of DVT and PE in 2004. 

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