Bevacizumab (Avastin®) is a recombinant humanised monoclonal antibody that is directed against the vascular endothelial growth factor (VEGF). It has been licensed since March 2005 by HSA for use in combination with intravenous 5-fluorouracil/folinic acid or intravenous 5-fluorouracil/folinic acid/irinotecan for the first-line treatment of patients with metastatic carcinoma of the colon or rectum.

Based on reviews of post-market and clinical trial reports, rare cases of hypertensive encephalopathy and reversible posterior leukoencephalopathy syndrome (RPLS) have been seen in patients on Avastin®.

A total of three confirmed cases of hypertensive encephalopathy have been reported in Avastin® clinical studies and in post-marketing experience worldwide, based on an estimated patients' exposure of 67,000. Hypertensive encephalopathy is manifested as severe hypertension associated with headache, nausea, vomiting, convulsions or confusion. In all the cases reported, the patients had a medical history of hypertension and experienced markedly increased blood pressure of 200mmHg systolic. One of these three cases resulted in a fatal outcome.¹

RPLS, a neurologic disorder, typically presents as headache, seizures and visual loss, and often occurs in the setting of accelerated hypertension.² It may develop in patients who have kidney failure, high blood pressure or who have a compromised immune system. This condition encompasses a spectrum of disorders, including hypertensive encephalopathy, eclampsia, thrombotic thrombocytopenic purpura/haemolytic uraemic syndrome, and is also associated with the use of other medicines like immunosuppressants. Brain imaging, particularly MRI, confirms the diagnosis of RPLS. Reports of patients with RPLS have been confirmed in four and suspected in ten patients receiving Avastin®. Two of these reports were recently published in the literature.³ The onset of symptoms was reported to occur from 16 hours to 1 year after starting Avastin®. None of these cases had resulted in death.

A direct cause and effect between Avastin® and these events has not been established but it cannot be ruled out. The majority of the reports stated above were for the treatment of conditions other than the licensed indications – metastatic carcinoma of the colon or rectum. Both hypertensive encephalopathy and RPLS are reversible if recognised and treated promptly.

HSA has not received any local reports pertaining to hypertensive encephalopathy and RPLS associated with the use of Avastin®. In-line with regulatory actions taken by regulatory agencies such as the Therapeutics Goods Administration of Australia, European Medicines Agency, Health Canada and the US Food and Drug Administration, the local package insert of Avastin® will be updated to reflect this new safety information.

1. Health Canada advisory, warnings and recalls for health professionals, October 2006. http://www.hc-sc.gc.ca/dhp-mps/medeff/advisories-avis/prof/2006/avastin_hpc-cps_e.html
   
   
2. Intern Med J 2005; 35:83-90.
   
   
3. N Engl J Med 2006; 354:980-2.