Summary Safety Review - MELATONIN (N-acetyl-5-methoxytryptamine) - Review of the Safety of Melatonin in Children and Adolescents

December 11, 2015

Product

MELATONIN (N-acetyl-5-methoxytryptamine)

Potential Safety Issue

Neurological side effects

Key Messages

• Melatonin is used to help adults, adolescents and children with sleep problems as an over-the-counter natural health product in Canada.
• After becoming aware of international reports about serious neurological side effects possibly associated with the use of melatonin in children and adolescents, Health Canada did a review of this safety issue in this age group.
• At the time of this review, there was conflicting data of neurological side effects in children and adolescents. As a result of this review, Health Canada will request further safety information from the market authorization holder and will continue to monitor for information about this safety issue. Parents and caregivers are encouraged to consult a healthcare professional before giving melatonin to children and adolescents.

Overview

After becoming aware of international reports about neurological side effects, such as anxiety, panic reaction, visual hallucinations and seizures, possibly associated with melatonin use in children and adolescents ranging from newborn to 18 years old (pediatric population), Health Canada did a review of this safety issue in this age group. The review took into consideration the information on this patient population from scientific and medical literature, Canadian and international adverse reaction reports as well as what is known about the use of this drug in Canada and internationally.

Use in Canada

• Melatonin was first licensed in Canada in 2005 as a natural health product ingredient. ^{Footnote 1}
• In Canada, this naturally occurring hormone is used in adults to help re-set the body's sleep-wake cycle and to reduce the time to fall asleep. It is also used to improve the quality of sleep in adults who experience sleep problems because of shift-work or jet lag.
• Melatonin should not be used for more than four weeks without consulting a healthcare professional.
• Health Canada has licensed over 500 natural health products that include melatonin as an ingredient for use by adults. They are available over-the-counter as capsules, tablets placed under the tongue (sublingual), liquids and gums. Since 2011, 2 multi-ingredient natural health products containing melatonin have been licensed for use in Canada in children 12 years and older. At the time of this review, Health Canada has not authorised any melatonin-containing products for use in children 11 years and younger.

Safety Review Findings

• At the time of the review, the Canada Vigilance Program^{Footnote 2} had received 18 Canadian reports of side effects associated with the use of natural health products containing melatonin in the pediatric population. The most frequently reported side effect was sleepiness. Although 5 cases were considered serious because they included symptoms of anxiety, panic reaction, visual hallucinations, and seizures, there was limited data to link these cases of side effects to the use of melatonin.
• A review of international data from the World Health Organization's database brought up 163 cases of side effects, of which 8 were from Canada, associated with the use of melatonin in the pediatric population. The most common side effects reported were general fatigue, aggression, abnormal dreams, and headache. Seventy-one cases were considered serious, but they could not be assessed further because the information contained in the reports was incomplete.
• The review found limited clinical data suggesting that melatonin shows benefits for treating sleep disorders when used for less than 4 months in those having disorders of brain function that affect emotion, learning, and memory (attention deficit hyperactivity disorder and autism spectrum disorders). The short term impact on the psychological development and the long term risk on growth in the pediatric population is still uncertain.

Conclusions and Actions

• As a result of the limited data about neurological side effects associated with the use of melatonin in the pediatric population, Health Canada is encouraging parents and caregivers to consult a healthcare professional before giving any natural health products containing melatonin to this age group, especially if they have serious medical conditions like hormonal, brain, heart, liver, or kidney diseases. Furthermore, healthcare professionals should be consulted if children are taking blood pressure, sedative, psychiatric, or immunosuppressive medications as there may be a risk of harmful interactions.
• Health Canada will continue to evaluate this safety issue by asking for information from the market authorization holder of the 2 melatonin natural health products used in children 12 years and older. In addition, Health Canada will proactively monitor for safety information related to the use of melatonin in the general pediatric population.

Additional Information

The analysis that was carried out for this safety review took into consideration information from scientific and medical literature, Canadian and international adverse reaction reports as well as what is known about the use of this drug in Canada and internationally.

For additional information, contact the Marketed Health Products Directorate.