Posology : מינונים

4.2    Posology and method of administration

Posology
Patients undergoing major orthopaedic or abdominal surgery
The recommended dose of fondaparinux is 2.5 mg once daily administered post-operatively by subcutaneous injection.

The initial dose should be given 6 hours following surgical closure provided that haemostasis has been established.


Treatment should be continued until the risk of venous thrombo-embolism has diminished, usually until the patient is ambulant, at least 5 to 9 days after surgery. Experience shows that in patients undergoing hip fracture surgery, the risk of VTE continues beyond 9 days after surgery. In these patients the use of prolonged prophylaxis with fondaparinux should be considered for up to an additional 24 days (see section 5.1).

Medical patients who are at high risk for thromboembolic complications based on an individual risk assessment
The recommended dose of fondaparinux is 2.5 mg once daily administered by subcutaneous injection.
A treatment duration of 6-14 days has been clinically studied in medical patients (see section 5.1).

Treatment of unstable angina/non- ST segment elevation myocardial infarction (UA/NSTEMI) The recommended dose of fondaparinux is 2.5 mg once daily, administered by subcutaneous injection.
Treatment should be initiated as soon as possible following diagnosis and continued for up to a maximum of 8 days or until hospital discharge if that occurs earlier.

If a patient is to undergo percutaneous coronary intervention (PCI), unfractionated heparin (UFH) as per standard practice should be administered during PCI, taking into account the patient’s potential risk of bleeding, including the time since the last dose of fondaparinux (see section 4.4). The timing of restarting subcutaneous fondaparinux after sheath removal should be based on clinical judgment. In the pivotal UA/NSTEMI clinical trial, treatment with fondaparinux was restarted no earlier than 2 hours after sheath removal.

Treatment of ST segment elevation myocardial infarction (STEMI)
The recommended dose of fondaparinux is 2.5 mg once daily. The first dose of fondaparinux is administered intravenously and subsequent doses are administered by subcutaneous injection.
Treatment should be initiated as soon as possible following diagnosis and continued for up to a maximum of 8 days or until hospital discharge if that occurs earlier.

If a patient is to undergo non-primary PCI, unfractionated heparin (UFH) as per standard practice should be administered during PCI, taking into account the patient’s potential risk of bleeding, including the time since the last dose of fondaparinux (see section 4.4). The timing of restarting subcutaneous fondaparinux after sheath removal should be based on clinical judgment. In the pivotal STEMI clinical trial, treatment with fondaparinux was restarted no earlier than 3 hours after sheath removal.

Patients who are to undergo coronary artery bypass graft (CABG) surgery In STEMI or UA/NSTEMI patients who are to undergo coronary artery bypass graft (CABG) surgery, fondaparinux where possible, should not be given during the 24 hours before surgery and may be restarted 48 hours post-operatively.

Special populations

Prevention of VTE following Surgery
In patients undergoing surgery, timing of the first fondaparinux injection requires strict adherence in patients ≥75 years, and/or with body weight <50 kg and/or with renal impairment with creatinine clearance ranging between 20 to 50 ml/min.

The first fondaparinux administration should be given not earlier than 6 hours following surgical closure. The injection should not be given unless haemostasis has been established (see section 4.4).


Renal impairment
• Prophylaxis of VTE –Fondaparinux should not be used in patients with creatinine clearance <20 ml/min (see section 4.3). Arixtra 2.5mg/0.6ml should not be used in patients with creatinine clearance in the range of 20 to 50 ml/min because adequate dosage reduction cannot be achieved (see sections 4.4 and 5.2). No dosage reduction is required for patients with mild renal impairment (creatinine clearance >50 ml/min).

• Treatment of UA/NSTEMI and STEMI - Fondaparinux should not be used in patients with creatinine clearance < 20 ml/min (see section 4.3). No dosage reduction is required for patients with creatinine clearance > 20 ml/min.

Hepatic impairment
Prevention of VTE and Treatment of UA/NSTEMI and STEMI - No dosing adjustment is necessary in patients with either mild or moderate hepatic impairment. In patients with severe hepatic impairment, fondaparinux should be used with care as this patient group has not been studied (see sections 4.4 and 5.2).

Paediatric population - Fondaparinux is not recommended for use in children below 17 years of age due to a lack of data on safety and efficacy.

Low body weight

Prevention of VTE and treatment of UA/NSTEMI and STEMI – Patients with body weight<50 kg are at increased risk of bleeding. Elimination of fondaparinux decreases with weight. Fondaparinux should be used with caution in these patients (see section 4.4).


Method of administration
• Subcutaneous administration
Fondaparinux is administered by deep subcutaneous injection while the patient is lying down. Sites of administration should alternate between the left and the right anterolateral and left and right posterolateral abdominal wall. To avoid the loss of medicinal product when using the pre-filled syringe do not expel the air bubble from the syringe before the injection. The whole length of the needle should be inserted perpendicularly into a skin fold held between the thumb and the forefinger; the skin fold should be held throughout the injection.

• Intravenous administration (first dose in patients with STEMI only) Intravenous administration should be through an existing intravenous line either directly or using a small volume (25 or 50ml) 0.9% saline minibag. To avoid the loss of medicinal product when using the pre-filled syringe do not expel the air bubble from the syringe before the injection. The intravenous tubing should be well flushed with saline after injection to ensure that all of the medicinal product is administered. If administered via a minibag, the infusion should be given over 1 to 2 minutes.

For additional instructions for use and handling and disposal see section 6.6.