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.
Refludan (Aventis Pharma)
vials containing 50 mg freeze dried powder
Approved indication: heparin-associated thrombocytopenia
Australian Medicines Handbook Section 7.1.1
Heparin can induce two types of thrombocytopenia. Type I occurs early in treatment and the platelet count soon returns to normal. Type II occurs after 5-10 days of treatment and can result in thromboembolism. Clotting occurs because the formation of a heparin-platelet complex induces the production of antibodies. These antibodies not only cause thrombocytopenia, but also activate the platelets. If untreated, heparin-induced thrombocytopenia can be fatal.
While the heparin can easily be stopped the prothrombotic state may persist. Lepirudin is therefore indicated for patients with Type II thrombocytopenia and its thromboembolic complications.
The drug is a recombinant form of hirudin, a substance produced by leeches. Lepirudin acts by inhibiting thrombin. This effect can be monitored by measuring the activated partial thromboplastin time.
Lepirudin has to be reconstituted and then injected intravenously. This bolus dose is followed by an infusion for 2-10 days. The dose is reduced if the patient has impaired renal function, as lepirudin is metabolised and excreted by the kidneys. A lower dose should also be used if the patient requires thrombolytic therapy.
In clinical trials, patients given lepirudin have been compared with historical controls. Approximately 74% of the patients responded to the treatment with an increased platelet count and an effective degree of anticoagulation. The incidence of new thromboembolic complications, death or the need to amputate a limb was reduced in comparison to the control group. After seven days of treatment the cumulative risk of these complications was 17% in the lepirudin patients and 25% in the control group.
The main adverse effect of lepirudin is bleeding. Thrombolytic therapy increases the risks. While bleeding from wounds and puncture sites is obvious, 9% of patients will suffer a fall in haemoglobin for no obvious reason. Other common problems are allergic reactions, bronchospasm and oedema. Approximately 40% of patients will develop antibodies to lepirudin. This may have implications if a patient requires a second course of treatment. Although the risk: benefit ratio is not clear, there are no specific treatments for heparin-associated thrombocytopenia, so there may be a role for lepirudin.