Why hasn't the TGA taken Stilnox off the market?

Behind the news

6 July 2012

This TGA behind-the-news article was published on 6 July 2012. Behind-the-news articles are published in response to issues that are of interest to the community at a point in time, for example, subjects that have been in the media.

As the medicines' watchdog, the TGA, has been closely monitoring the sleeping drug, zolpidem (Stilnox) for many years.

While there is evidence of some extreme side effects in some people, the TGA has determined that used properly this is a medicine of value to some patients, particularly with severe insomnia, and should remain available for use in Australia.

In 2008 the TGA and its expert advisory committee at the time, the Adverse Drug Reaction Advisory Committee (ADRAC), recommended that the TGA place a black box warning on the medicine which is the most extreme warning available to the TGA to alert people to the possible side effects of a medicine. The warning is highlighted by a bold black surround or "box". The wording of the boxed warning for zolpidem is:

"Zolpidem may be associated with potentially dangerous complex sleep-related behaviours which may include sleep walking, sleep driving and other bizarre behaviours. Zolpidem is not to be taken with alcohol. Caution is needed with other CNS depressant drugs. Limit use to four weeks maximum under close medical supervision."

In addition the pack size was reduced and a warning on the front of the package was added that says it should not be taken with alcohol which, on investigation, accounted for the vast majority of adverse events in patients even though the Product Information has always specifically said that drinking while taking this drug was prohibited.

Also in 2008 the then National Drugs and Poisons Schedule Committee (NDPSC) considered the scheduling of zolpidem because of concerns relating to reports of potential abuse of this substance. It concluded that the current Prescription Only status of zolpidem remains appropriate and there was no compelling evidence presented to the NDPSC that the abuse potential of zolpidem required it to be rescheduled.

In March 2012, an article was published by Professor Darke et al in the Journal of Forensic Sciences titled "Toxicology and Characteristics of Deaths Involving Zolpidem in New South Wales, Australia 2001-2010", the authors noted that a high degree of caution was needed in prescribing patients zolpidem especially with co-existing mood disorders. The article did not specifically look at the effect of the introduction of the black box warning in 2008 in reducing deaths associated with zolpidem and the use of other CNS depressant drugs.

Four weeks ago, the TGA issued its latest advice to doctors on the use of and safety of Stilnox in a published article in the TGA Medicines Safety Update.

The adverse events reported in the article were across the period 1 January 2009 to 30 April 2012. Over this period the annual numbers of these types of adverse events have been decreasing which suggests that the boxed warning added to the Product Information (PI) and other changes made in 2008 has been effective in ensuring the safer use of zolpidem.

There is no specific new safety signal of concern to the TGA that would require the TGA to take any further action at this time.

The purpose of the MSU article was to remind prescribers of the importance of following the advice in the PI and of continuing to report any adverse events. Such reports enable the TGA to continue monitoring the safety of the drug.