Summary Safety Review - SEVORANE AF (sevoflurane) - Severe low heart rate in children with Down syndrome

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: 2015-05-13

Product

SEVORANE AF (sevoflurane) and generics

Potential Safety Issue

Severe low heart rate in children with Down syndrome

Key Messages

  • Sevoflurane is used as a general anaesthetic during surgery to make a patient unconscious and unable to feel pain.
  • Health Canada noted differences between the sevoflurane prescribing information of different companies regarding the potential risk of severe lowering of the heart rate (severe bradycardia) in children with Down syndrome. Health Canada initiated a safety review to evaluate this issue further.
  • The Canadian prescribing information for the product marketed under the brand name SEVORANE AF has been updated to highlight the occurrence of cases of bradycardia in pediatric patients with Down syndrome exposed to sevoflurane. Manufacturers of generic versions of this drug are in the process of updating their product information.

Overview

A safety review was initiated to evaluate the possible link between a severe lowering of the heart rate (a medical condition known as severe bradycardia) and the use of the general anaesthetic sevoflurane (SEVORANE AF and generics) in children with Down syndrome. This issue was identified by Health Canada during routine review of safety information provided by the manufacturer.

Use in Canada

  • Sevoflurane is used as a general anaesthetic during surgery in adults and children to make them unconscious and unable to feel pain. It is used in hospitals and is administered only by persons trained in the administration of general anaesthesia.
  • In Canada, sevoflurane is the most widely used inhalational general anaesthetic. Its use has remained constant over the last five years.
  • Sevoflurane is administered through a vaporizer mask and is breathed into the lungs (inhalational).
  • It has been marketed in Canada since 1995.

Safety Review Findings

  • Bradycardia is defined as a heart rate below the lowest normal values which vary according to age group. If bradycardia is severe, slowing of the heart can occur to the point that the heart stops. Severe bradycardia can be treated with certain medications and interventions to restore normal heart rate. Complications of anaesthesia can occur in all patient populations. However some complications including bradycardia are more likely to occur in people with Down syndrome due to pre-existing heart defects and/or problems with the nervous system and muscles (neuromuscular problems).
  • At the time of the review, the Canadian prescribing information for sevoflurane products documented the incidence of bradycardia in children. Although the information available to prescribers did not directly address the risk of severe bradycardia in children with Down syndrome, it did address the risk in vulnerable children with and without additional medical conditions associated with neuromuscular problems which would include children with Down syndrome.
  • At the time of the review, Health Canada had not received any reports of sevoflurane-associated bradycardia in children with Down syndrome. International reports of severe bradycardia in children with Down syndrome suspected to be associated with sevoflurane use were provided by the company that first marketed sevoflurane.
  • A review of the scientific and medical literature identified a number of research articles relevant to the topic of bradycardia in children with Down syndrome associated with sevoflurane use. The information contained in these articles was limited in terms of both the number and quality of case reports. However, these articles highlighted the possibility of sevoflurane-induced bradycardia in children with Down syndrome. At the time of the review, the Canadian prescribing information was similar to the United States and European prescribing information with respect to the risk of bradycardia in vulnerable pediatric populations, especially those with problems with the nervous system and muscles (neuromuscular problems).

Conclusions and actions

  • The risk of bradycardia (slowing of the heart rate) with sevoflurane should be considered for all children. The prescribing information for sevoflurane mentions the risk of bradycardia in healthy children and in children with neuromuscular problems. It is being updated to mention the occurrence of cases of bradycardia in children with Down syndrome.
  • Health Canada will continue to monitor adverse reaction information involving sevoflurane, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new information on this risk is identified.

Additional information

The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of this drug both in Canada and internationally.

For additional information, contact the Marketed Health Products Directorate.

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