Fondaparinux Warfarin

The most extensively studied drugs for the prevention of VTE are unfractionated heparin (UFH), the low-molecular-weight heparins (LMWHs dalteparin, enoxaparin, and tinza-parin), fondaparinux, and warfarin.2 The LMWHs and fondaparinux provide superior protection against VTE when... 

Hold or adjust warfarin dose as necessary. If the patient is being treated with UFH, measure aPTT daily (or antifactor Xa activity), and adjust dose if necessary. If the patient is being treated with an LMWH or fondaparinux, continue therapy. 

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

Acute DVT and PE treatment In patients with acute symptomatic DVT and in patients with acute symptomatic PE, the recommended dosage of fondaparinux is 5 mg (body weight less than 50 kg), 7.5 mg (body weight 50 to 100 kg), or 10 mg (body weight greater than 100 kg) by subcutaneous injection once daily. Continue fondaparinux treatment for at least 5 days until a therapeutic oral anticoagulant effect is established (international normalized ratio [INR] 2 to 3). Initiate concomitant treatment with warfarin as soon as possible, usually within 72 hours. The usual duration of administration of fondaparinux is 5 to 9 days. 

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. 

Warfarin Clopldogrel Enoxaparln Dalteparln TInzaparIn Fondaparinux Blvallrudln Xlmelagatran... 

There was no pharmacodynamic interaction of subcutaneous fondaparinux 4 mg with warfarin in 12 healthy men (25). 

Faaij RA, Burggraaf J, Schoemaker RC, Van Amsterdam RG, Cohen AF. Absence of an interaction between the synthetic pentasaccharide fondaparinux and oral warfarin. Br J Clin Pharmacol 2002 54(3) 304-8. 

Clinically important, potentially hazardous interactions with anisindione, anticoagulants, atorvastatin, dabigatran, dicumarol, fondaparinux, simvastatin, warfarin... 

In the absence of contraindications, the treatment of VTE initially should include a rapid-acting anticoagulant (e.g., unfractionated heparin [UFH], a low-molecular-weight heparin [LMWH], or fondaparinux) overlapped with warfarin for at least 5 days and until the patient s international normalized ratio (INR) is greater than 2.0. Anticoagulation therapy should be continued for a minimum of 3 months. The duration of anticoagulation therapy should be based on the patient s risk of VTE recurrence and major bleeding. 

Only a handful of smdies have formally evaluated the cost-effectiveness of VTE prevention strategies. The acquisition costs of graduated compression stockings, heparin, and warfarin are considerably less than those of the LMWHs, DTls, and fondaparinux. However, the acquisition cost for drug therapy is relatively small when compared with the overall cost of care. Economic analyses must take into account the efficacy of the strategy, treatment complications, and monitoring costs. 

UFH and warfarin. However, because of their superior effectiveness, the LMWHs have a significantly lower cost per DVT and PE avoided. Based on typical drug acquisition costs, the LMWHs and fondaparinux appear to be a cost-effective choice in the highest-risk patient populations. ... 

Duration of acute treatment Treatment with UFH, FMWH, or fondaparinux should be overlapped with warfarin for at least 5 days and can be stopped when the INR is >2.0. Most patients should have warfarin started at the same time as UFH, FMWH, or fondaparinux. 1C... 

Medications Continue LMWH or fondaparinux and warfarin as directed. 

Warfarin tablets take several days to begin to work LMWH or fondaparinux injections work right away, so at first, LMWH or fondaparinux injections and warfarin tablets are used together. 

When the warfarin has become effective, you will be able to stop the LMWH or fondaparinux injections you will continue to take warfarin tablets for 3 to 6 months or more to prevent blood clots from returning. 

It is important for you to administer your LMWH or fondaparinux and warfarin exactly as directed. 

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. 

Warfarin monotherapy is an unacceptable choice for the acute treatment of VTE because it does not produce a rapid anticoagulation effect and is associated with a high incidence of recurrent thromboembolism. However, warfarin is very effective in the longterm management of VTE and should be started concurrently with UFH, LMWH, or fondaparinux therapy. The acute treatment regimen should overlap with warfarin therapy for at least 5 days and until a therapeutic INR has been achieved. The initial dose of warfarin should be 5 to 10 mg (see Fig. 19-8), and it should be adjusted periodically to achieve and maintain an INR between 2.0 and 3.0. 

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