Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.
Arixtra (Sanofi-Synthelabo)
2.5 mg/0.5 mL in pre-filled syringes
Approved indication: thromboembolic prophylaxis
Australian Medicines Handbook Section 7.1
Low molecular weight heparins, such as enoxaparin, can be used to prevent thromboembolism in surgical patients. They act by catalysing the inactivation of Factor Xa (see 'The new heparins' Aust Prescr 1996;19:104-8).
Fondaparinux is a pentasaccharide which also acts by potentiating the neutralisation of Factor Xa. This activity reaches a maximum three hours after a subcutaneous injection. There is no effect on platelet function, bleeding time or fibrinolysis.
Most of the dose stays in the circulation as it binds to antithrombin III. The half-life of fondaparinux is 17-20 hours. As the drug is mainly excreted unchanged in the urine it is contraindicated in patients with severe renal impairment. Clearance is also reduced in the elderly.
In a study of 1250 patients with a fractured femur, fondaparinux was compared with enoxaparin. The patients were treated once a day for at least five days, with most stopping their prophylaxis by the ninth day after surgery. At day 11, 8.3% of the patients given fondaparinux had evidence of a venous thromboembolism. This incidence was significantly less than in the enoxaparin group as 19% of those patients had thromboembolism.1
Another study involved 724 patients having elective knee surgery. The incidence of venous thromboembolism 11 days after surgery was 13% in patients treated with fondaparinux. Although the patients taking enoxaparin were given 30 mg twice daily, the incidence of thromboembolism was 28%.2
The comparative clinical trials used venography to show that fondaparinux had greater efficacy than enoxaparin. There were however no significant differences in the incidence of symptomatic thromboembolism or fatal pulmonary embolism.
As fondaparinux has an antithrombotic action, bleeding is its major serious adverse effect. In the clinical trials 2-3% of patients had a serious haemorrhage. Fondaparinux caused significantly more bleeding than enoxaparin after knee surgery.2 Other adverse reactions reported in the trials of fondaparinux include anaemia, thrombocytopenia, altered liver function and injection site reactions. Particular caution is needed if fondaparinux is given to patients who have had spinal or epidural anaesthesia. There is a risk that a spinal or epidural haematoma may develop with the risk of long-term paralysis. Fondaparinux has no antidote.
