Summary Safety Review - IMOVANE (zopiclone) - Next-Day Impairment

Review decision

A Summary Safety Review complements other safety related information to help Canadians make informed decisions about their use of health products. Each summary outlines what was assessed in Health Canada’s review, what was found and what action was taken by Health Canada, if any.


Issued: 2014-11-21

issue

A safety review was initiated to evaluate the currently available information regarding the risk of next-day impairment, including altered driving skills leading to car accidents, after exposure to IMOVANE and generic zopiclone products. The review was prompted by the results of recent studies that reported driving impairment the morning following bedtime use of hypnotics, especially at the higher recommended doses.

Background

Approved use of zopiclone in Canada

IMOVANE and generic zopiclone products are approved for short-term use (up to 7 to 10 consecutive days) by adult patients with insomnia characterized by difficulties falling asleep, nighttime awakenings and/or early morning awakenings causing impaired daytime functioning.

Zopiclone products are currently marketed in Canada as 5 mg and 7.5 mg tablets. The 7.5 mg tablet can be split in half to achieve a lower dose (i.e., 3.75 mg). Zopiclone is taken at bedtime.

Next-day impairment

Next-day impairment with the use of hypnotics such as zopiclone is generally recognized as a decreased ability to be alert the next day after taking the medicine. It can include symptoms such as daytime sleepiness, impaired hand eye coordination, decreased mental sharpness and related motor functions. Some patients may have zopiclone blood levels in the morning that are high enough to produce psychological and motor impairment.

Objective

To assess the available evidence concerning the risk of next-day impairment associated with the use of zopiclone. This review considered information from Canadian adverse reaction reports, scientific literature, international safety data, as well as what is known about the use of zopiclone products both in Canada and internationally. The review evaluated the risk and suggested ways to minimize it.

Key findings

Use of zopiclone products in Canadaa

From 2008 to 2013, Canadian pharmacies dispensed more than 28 million prescriptions of zopiclone products, mostly in the 7.5 mg tablet strength. It is unclear what percentage of these prescriptions was written for use as one half of a 7.5 mg tablet. Zopiclone is generally prescribed to adults (more than 18 years of age). More than one third of all patients receiving zopiclone in Canada are 65 years of age or older.

Canadian reports of next-day impairment associated with zopiclone

At the time of this review, Health Canada had received 5 reports of next-day impairment suspected of being associated with zopiclone use. None of these cases resulted in an accident. In one case, excessive daytime drowsiness and fatigue were considered probably related to zopiclone therapy. In the remaining 4 cases, the reaction (e.g., confusion, fatigue, sleepiness, or drowsiness) could also be explained by other factors.

Scientific reports

Evidence from studies has shown that healthy individuals taking zopiclone 7.5 mg at bedtime may have a decreased ability for vehicle control the morning after. The subjects are generally not aware of the possibility for this impairment.

Conclusions and actions

  • The current available evidence suggests that next-day impairment may occur in patients the morning following bedtime zopiclone use, including altered driving skills which could lead to accidents.

    Health Canada actions:

    1. Health Canada has worked with the manufacturer of IMOVANE to include additional details in the prescribing information to further emphasize the risk of next-day impairment, and to include patient counselling information. Manufacturers of generic versions of zopiclone will also update their product information.
    2. As part of this discussion, the manufacturer provided new information to Health Canada that showed a risk of driving impairment with the 7.5 mg dose. The risk is increased in the elderly, other special populations at higher risk (e.g., in patients with poor liver or renal function), and patients who are taking at the same time other drugs that decrease the metabolism of zopiclone.  Health Canada has approved new dosing recommendations for zopiclone, i.e., a lower starting dose of 3.75 mg for all patients, and a maximum daily dose of 5 mg in the special populations mentioned above.
    3. A risk communication has been issued to healthcare professionals and the  public to inform them of the new dosing recommendations and to remind them about the risks of next-day impairment and ways to minimize it.

References

  1. Verster JC, Spence DW, Shahid A, et al. Zopiclone as positive control in studies examining the residual effects of hypnotic drugs on driving ability. Current Drug Safety 2011;6(4):209-18.
  2. Leufkens TR, Ramaekers JG, de Weerd AW, et al. Residual effects of zopiclone 7.5 mg on highway driving performance in insomnia patients and healthy controls: a placebo controlled crossover study. Psychopharmacology (Berl). 2014;231(14):2785-98.

Footnotes

  1. IMS utilization data provided by: IMS Health Canada Inc. An external party cannot refer to nor use IMS data, which have been generated by Health Canada, without a Third Party Agreement in place.
  2. This list of references is not intended to be exhaustive. References have been selected as suggestions for further reading and reflect the most current information at the time of the safety review.

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