Desirudin

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.

Revasc (Aventis Pharma)
vials containing 15 mg as lyophilised powder
Approved indication: prevention of thromboembolism
Australian Medicines Handbook Section 7.1

The influence of the leech on medical practice seems set to continue into the next century following the approval of desirudin. This is a recombinant product with a structure that is almost identical to hirudin, an anticoagulant found in the saliva of Hirudo medicinalis. It has been approved for the prevention of thromboembolism after hip replacement surgery.

Desirudin is reconstituted with mannitol and injected subcutaneously no more than 30 minutes before elective hip replacement. Twice daily injections continue for 9-12 days until the patient is walking. The injections should be rotated through at least four different sites.

The maximum plasma concentrations occur within three hours of injection. Desirudin is partly metabolised before excretion. Approximately half the dose is excreted unchanged in the urine. The APTT should be monitored in patients with impaired hepatic or renal function.

Desirudin acts by specifically inhibiting thrombin. As desirudin can inactivate thrombin bound to fibrin, it has a potential advantage over heparin which also has a less specific action.

A double-blind trial has compared subcutaneous heparin and desirudin in 1119patients having hip surgery.1 Patients given the dose of desirudin recommended for use in Australia (15 mg twice daily) were significantly less likely to develop deep vein thrombosis than those given unfractionated heparin(18.4% versus 34.2%). The respective frequencies of proximal thrombosis were3.1% versus 19.6%. The frequency of bleeding complications was similar in both groups.

Episodes of bleeding occurred in 13% of patients given desirudin in clinical trials. There is no antidote. Other adverse effects include haematoma, injection site masses and secretion from the wound.

While hirudin is more effective than subcutaneous unfractionated heparin, its role in clinical practice is not yet clear. There needs to be a comparison between hirudin and other approaches to preventing thrombosis such as adjusted dose intravenous heparin or subcutaneous low molecular weight heparin.


References

  1. Eriksson BI, Ekman S, Kalebo P, Zachrisson B, Bach D, Close P. Prevention of deep-vein thrombosis after total hip replacement: direct thrombin inhibition with recombinant hirudin, CGP 39393. Lancet 1996;347:635-9.