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.
Freedox (Pharmacia & Upjohn)
1.5 mg/mL in 100 mL vials
Indication: aneurysmal subarachnoid haemorrhage
Patients who rupture an intracranial aneurysm have a high mortality. Those who survive the subarachnoid haemorrhage are likely to be left with a neurological deficit. One cause of the tissue damage may be the production of toxic super oxideradicals. This can contribute to the cerebral vasospasm which occurs after the acute haemorrhage. Tirilazad is thought to promote tissue survival by inhibiting lipid peroxidation.
The drug is a new chemical entity. It is a non hormonal 21-aminosteroidand is lipid soluble. The vials of tirilazad have to be kept in a refrigerator(2-8oC) and protected from light. The solution is diluted and infused over 10-30 minutes every 6 hours starting within 48 hours of the haemorrhage. Treatment continues for 8-10 days. Most of the patients in clinical trials of tirilazad have also been given nimodipine to prevent cerebral vasospasm.
Although animal studies show that tirilazad improves the functional outcome, a significant benefit has not been confirmed in all clinical trials. Of the two studies included in the product information, only one showed a significant improvement in survival. Closer examination reveals that only male patients get a significant benefit from treatment. The drug is therefore only approved for men.
The common adverse effects are reactions at the site of infusion and changes in liver function. Tirilazad is metabolised in the liver and its clearance is increased 50% by phenytoin.
