Treatment of acute thromboembolism (DVT) and acute pulmonary embolism (EP), excluding patients, hemodynamically unstable patients or patients requiring thrombolysis or embolectomy, pulmonary Br>

Dosage

The recommended dosage of fondaparinux is 7.5 mg (for patients, weighing between 50 and 100 kg) once daily, administered by subcutaneous injection. For patients weighing less than 50 kg, the recommended dosage is 5 mg. For patients weighing more than 100 kg, the recommended dosage is 10 mg.


Populations, special

Elderly - No dose adjustment is required. In patients 75 years of age and older, fondaparinux should be used with caution because of impaired renal function and age (see Warnings and Precautions for Use). Code>
Renal Insufficiency - fondaparinux should be used with caution in patients with moderate renal impairment (see section 4.4). >
There is no experience in the subgroup of patients with high (> 100 kg) and moderate renal insufficiency (creatinine clearance between 30 and 50 ml / min). In this subgroup, after an initial dose of 10 mg once daily, a reduction of the daily dose to 7.5 mg may be considered on the basis of pharmacokinetic modeling data (see section Custody and precautions, employment).

Fondaparinux should not be used in patients with severe renal insufficiency (creatinine clearance
Pediatrics - The use of fondaparinux is not recommended in children under the age of 17. Due to insufficient tolerance and efficacy data (see section 5.1 Pharmacokinetic properties and properties ).

Administration mode

Fondaparinux should be injected deep subcutaneously, with the patient in an extended position. The injection sites should be alternated between the anterolateral and posterolateral belt alternately on the right side and on the left side. To prevent any loss of medication when using the syringe, pre-filled, do not purge the air bubble from the syringe before performing the injection. The needle should be inserted perpendicularly over its entire length in the thickness of a skin fold made between the thumb and forefinger and this skin fold should be maintained throughout the duration of the injection. Code>
For additional instructions on use, handling and disposal, see section Instructions for Use, Handling and Disposal.
The solution is clear and colorless to slightly yellow.

Class: Pharmacotherapeutic: Anti-thrombotic agent, ATC code, B01AX05

Effects, pharmacodynamics

Fondaparinux is a synthetic and selective inhibitor of Factor X, activated (Xa). The antithrombotic activity of fondaparinux is the result of selective inhibition of Factor Xa by antithrombin III (antithrombin). By selectively binding to antithrombin, fondaparinux potentiates (about 300-fold), natural inhibition of Factor Xa by antithrombin, inhibition of factor Xa interrupts the cascade of coagulation, inhibiting both Formation of thrombin as thrombus development. Fondaparinux does not inactivate thrombin (Factor II activated) and has no effect on platelets.

At the doses used, fondaparinux does not clinically relevant routine coagulation tests such as activated partial thromboplastin time (ACT), activated coagulation time (ACT), or Prothrombin (TP) / International Normalized Ratio (INR) in plasma, nor time, bleeding or fibrinolytic activity. At higher doses the TCA may be moderately altered. However, rare spontaneous reports of elevation of the TCA were recorded.


At the 10 mg dose used in the interaction studies, fondaparinux did not significantly alter the effect of warfarin on INR

There is no cross-reactivity between fondaparinux and serum of patients with heparin-induced thrombocytopenia.

Clinical studies

The clinical development program of fondaparinux in the treatment of venous thromboembolic events has been designed to demonstrate the efficacy of fondaparinux in the treatment of deep vein thrombosis (DVT) and pulmonary embolism (EP). More than 4874 patients were studied in controlled trials of Phase II and III.

Treatment of thrombosis, deep veins

In a randomized, double-blind, clinical trial in patients with a confirmed diagnosis of deep vein thrombosis, symptomatic acute, fondaparinux administered as a subcutaneous injection per day of 5 mg (weight less than 50 kg ), 7.5 mg (weight between 50 and 100 kg) or 10 mg (weight greater than 100 kg), was compared to enoxaparin 1 mg / kg administered subcutaneously twice; day. A total of 2192 patients were treated, in both groups the patients were treated for at least 5 days and up to 26 days (mean 7 days). Both groups of patients received an anti-vitamin K treatment, usually initiated within 72 hours after the first administration of the products studied and continued for 90 ± 7 days with regular dosage adjustments to achieve The primary efficacy endpoint was a combination of recurrent, confirmed recurrence of venous thromboembolic events, nonfatal symptomatic venous thromboembolic events (ETEV), and fatal ETEV reported within 97 days. It was demonstrated that fondaparinux is non-inferior to enoxaparin (ETEV rate of 3.9% and 4.1%, respectively)

During the initial phase of treatment, major bleeding was observed in 1.1% of patients treated with fondaparinux and 1.2% with those treated with enoxaparin.

Treatment of pulmonary embolism

A randomized, open-label, clinical trial was conducted in patients with symptomatic acute pulmonary embolism and was confirmed by objective tests (pulmonary scan, pulmonary angiography or helical tomography). Patients requiring thrombolysis, embolectomy, or placement of a cellar filter were excluded. Randomized patients may have been treated, initially with non-fractionated heparin during the selection phase, but patients treated for more than 24 hours with anticoagulants at therapeutic doses or with uncontrolled hypertension, Were excluded. Fondaparinux administered as a subcutaneous injection per day of 5 mg (weight less than 50 kg), 7.5 mg (weight between 50 and 100 kg) or 10 mg (higher weight 100 kg) Was compared to unfractionated heparin, administered in bolus IV (5000 IU) followed by adjusted continuous IV infusion, to maintain the TCA between 1.5 and 2.5 times the control value. A total of 2184 patients were treated in both groups and treated for at least 5 days and up to 22 days (on average 7 days). Both groups of patients received anti-vitamin K treatment, usually initiated within 72 hours after the first administration of the products, studied and continued for 90 ± 7 days with regular adjustments of the dosage to achieve An INR of 2-3. The primary efficacy endpoint was a combined endpoint, associating confirmed recurrence of symptomatic non-fatal ETEV and fatal ETEV reported within 97 days. Fondaparinux was demonstrated to be not less than the unfractionated heparin (ETEC level of 3.8% and 5.0%, respectively).
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During the initial phase of treatment, major bleeding was observed in 1.3% of patients treated with fondaparinux and 1.1% in those treated with heparin, unfractionated.
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Pharmacokinetic research study of dose of fondaparinux in children with venous thrombosis,

A clinical study was conducted on an open-label basis in 24 children, 10 from 1 to 5 years of age, weighing between 8 and 20 kg, 7 from 6 to 12 years, weighing between 17 and 47 kg And 7 aged 13 to 18 with a body weight between 47 and 130 kg) with diagnosed venous thrombosis at baseline and treated with fondaparinux
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Most of the children were of Hispanic (67%) and male (58%).

Fondaparinux was administered at an initial dose of 0.1 mg / kg subcutaneously once daily, dose a was adjusted to achieve maximum concentrations of fondaparinux sodium of 0.5 to 1 mg / L after 4 hours.

The median duration of treatment in this study was 3.5 days.
Most children (88%) reached target concentrations of fondaparinux 4 hours after the first dose of fondaparinux.
Two patients presented bleeding during the study.