Route of administration: ARIXTRA must not be administered intramuscularly (see Dosage & Administration).
2.5 mg/0.5 mL: PCI and risk of guiding catheter thrombus: In STEMI patients undergoing primary PCI for reperfusion, the use of ARIXTRA prior to and during PCI is not recommended. In UA/NSTEMI and STEMI patients undergoing non-primary PCI, the use of ARIXTRA as the sole anticoagulant during PCI is not recommended, therefore UFH should be used according to standard practice (see Dosage & Administration).
In a clinical trial comparing two dose regimens of UFH during non-primary PCI, fondaparinux- treated UA/NSTEMI patients were randomized to receive either 'standard dose UFH' (median dose 85U/kg) or 'low dose UFH' (median dose 50U/kg). The incidence of peri-PCI major bleeding was 1.2% with 'standard dose UFH' and 1.4% with 'low dose UFH' (see Pharmacology: Pharmacodynamics: Clinical Studies under Actions).
Clinical trials have shown a low but increased risk of guiding catheter thrombus in patients treated solely with ARIXTRA for anticoagulation during PCI compared to control. Incidences in non-primary PCI in UA/NSTEMI were 1.0% vs 0.3% (ARIXTRA vs. enoxaparin) and in primary PCI in STEMI were 1.2% vs 0% (ARIXTRA vs. control). In fondaparinux-treated UA/NSTEMI patients randomised to receive "standard dose" or "low dose" regimens of UFH during non-primary PCI, the incidences of catheter thrombus were 0.1% and 0.5%, respectively (see Pharmacology: Pharmacodynamics: Clinical Studies under Actions).
Haemorrhage: ARIXTRA, like other anticoagulants must be used with caution in conditions with an increased risk of haemorrhage, (such as congenital or acquired bleeding disorders, active ulcerative gastrointestinal disease, recent intracranial haemorrhage, shortly after brain, spinal or ophthalmic surgery).
Prevention and treatment of VTE: Other medicinal products enhancing the risk of haemorrhage, with the exception of vitamin K antagonists used concomitantly for treatment of VTE, should not be administered with ARIXTRA. If co-administration is essential, close monitoring is recommended (see Interactions).
2.5 mg/0.5 mL: Prevention of VTE following surgery (timing of first ARIXTRA Injection): The timing of the first injection requires strict adherence. The first dose should be given no earlier than 6 hours following surgical closure, and only after haemostasis has been established. Administration before 6 hours has been associated with an increased risk of major bleeding. Patient groups at particular risk are those from 75 years of age, body weight of less than 50 kg, or renal impairment with creatinine clearance less than 50 ml/min.
Treatment of UA/NSTEMI and STEMI: ARIXTRA should be used with caution in patients who are being treated concomitantly with other medicinal products that increase the risk of haemorrhage (such as GPIIb/IIIa inhibitors or thrombolytics).
Spinal/epidural anaesthesia/spinal puncture: Epidural or spinal haematomas that may result in long-term or permanent paralysis can occur with the use of anticoagulants and spinal/epidural anaesthesia or spinal puncture. The risk of these rare events may be higher with post-operative use of indwelling epidural catheters or the concomitant use of other medicinal products affecting haemostasis.
Low body weight: Patients with body weight less than 50 kg are at increased risk of bleeding. Elimination of ARIXTRA decreases with weight decrease. ARIXTRA should be used with caution in these patients (see Dosage & Administration).
Heparin Induced Thrombocytopenia: ARIXTRA does not bind to platelet factor 4 and does not cross-react with sera from patients with Heparin Induced Thrombocytopenia (HIT)-type II. It should be used with caution in patients with a history of HIT. The efficacy and safety of ARIXTRA have not been formally studied in HIT-type II. Rare spontaneous reports of HITS in patients treated with ARIXTRA have been received. To date a causal associated between treatment with ARIXTRA and the occurrence of HIT has not been established.
Latex Allergy: The needle shield of the pre-filled syringe contains dry natural latex rubber that has the potential to cause allergic reactions in latex sensitive individuals.
Effects on Ability to Drive and Use Machines: No studies on the effect on the ability to drive and to use machines have been performed.
Renal impairment: The plasma clearance of fondaparinux decreases with the severity of renal impairment, and is associated with an increased risk of haemorrhage (See Pharmacology: Pharmacokinetics under Actions). Due to the limited clinical data available, ARIXTRA should not be used in patients with severe renal impairment (creatinine clearance less than 30 ml/min).
2.5 mg/0.5 mL: There are limited clinical data available on the use of ARIXTRA for the treatment of UA/ NSTEMI and STEMI in patients with creatinine clearance between 20 to 30 ml/min. Therefore the physician should determine if the benefit of treatment outweighs the risk (see Dosage & Administration and Pharmacology: Pharmacokinetics under Actions). ARIXTRA is not recommended in patients with a creatinine clearance of less than 20 ml/min.
Severe hepatic impairment: In patients with an elevation in prothrombin time, the use of ARIXTRA should be considered with caution, because of an increased risk of bleeding due to a possible deficiency of coagulation factors in patients with severe hepatic impairment (see Dosage & Administration).
Use in Elderly: The elderly population is at increased risk of bleeding. As renal function generally decreases with age, elderly patients may show reduced elimination and increased exposure of ARIXTRA. ARIXTRA should be used with caution in elderly patients (see Dosage & Administration).