In this week's BMJ, a senior doctor advises caution over the use of the antiviral drug oseltamivir (Tamiflu).
His concern follows advice by the Japanese authorities in March 2007 against prescribing oseltamivir to adolescents after the separate suicides of two 14 year olds who jumped to their deaths while taking the drug.
AdvertisementSo far, oseltamivir has been thought to be well tolerated and safe, but the recent events in Japan have prompted a reappraisal, writes Simon Maxwell from the University of Edinburgh.
Before 2007, there had already been more than 100 reports of neuropsychiatric events (including delirium, convulsions, and encephalitis) with oseltamivir in children, almost entirely from Japan, which has the highest usage of oseltamivir worldwide. But a Food and Drug Administration (FDA) review concluded that these events were not clearly drug related.
Since last November, the FDA has required that doctors be warned that patients should be closely monitored for signs of abnormal behaviour throughout the treatment period and the European Medicine Evaluation Agency (EMEA) took similar steps in February.
In the UK, oseltamivir is a "black triangle" drug so it remains under more intensive surveillance and healthcare professionals are asked to report all minor as well as serious adverse events.
The controversy about oseltamivir is a further reminder that, although common adverse effects of a drug may emerge in prelicensing studies, the detection of rarer and potentially more serious events has to await exposure of large numbers of patients, he says.
In the light of these concerns, how should prescribers proceed?
There seems little doubt that oseltamivir reduces the number and seriousness of flu episodes when used as treatment and prophylaxis, he says. However, the impact of such events in otherwise healthy people is usually modest and of short duration, so they should be encouraged to use conservative strategies such as resting, increasing fluid intake, and taking simple analgesics.
In people at higher risk of serious complications the potential benefit of treatment seems greater, although convincing evidence about reductions in hospital admission or mortality is still awaited, he writes. In these groups, vaccination still offers a cost effective first line of defence.