Safety Information

Early Warning System - Alert Communication

Codeine – new restrictions on use in children and young adults

13 August 2018

Products Affected
Information for consumers and caregivers
Information for healthcare professionals
Data Summary
What actions are Medsafe taking?
Further information

How to report adverse events

Codeine is most often used to relieve pain. It is also used in cough and cold medicines to suppress dry cough. The effects of codeine only occur after it has been changed to morphine in the body.

Medsafe and the Medicines Adverse Reactions Committee (MARC) have reviewed the safety of codeine and concluded that the risk of harm is unacceptable in children. The MARC has therefore recommended changes to the age restrictions for codeine. This alert provides you with information about these changes and why codeine should not be used in children.

Products Affected

All medicines that contain codeine.

Information for consumers and caregivers

  • Codeine can cause serious breathing problems in children that could result in death.
    Therefore:
    • Do not use any medicines containing codeine in children aged less than 12 years.
    • Do not use any cough medicines containing codeine in adolescents aged less than 18 years.
    • Do not use any medicines containing codeine in adolescents aged less than 18 years to control pain after surgery to remove tonsils or adenoids.
    • Do not use any medicines containing codeine in adolescents aged less than 18 years who may have breathing problems (eg, if they have asthma or sleep apnoea).
    • Do not use medicines containing codeine if you are breastfeeding your infant.
  • Anyone taking codeine should get urgent medical help if they experience nausea, vomiting, extreme sleepiness, drowsiness, confusion, shallow breathing, or if they are difficult to wake.
  • See your doctor or pharmacist for advice on how to manage pain in children.

 

Information for healthcare professionals

  • Genetic polymorphism of the CYP2D6 gene results in significant variation between individuals in the efficiency of codeine metabolism to morphine.
  • Ultra-rapid metabolisers are at increased risk of morphine toxicity (including respiratory depression), while poor metabolisers obtain little analgesic benefit from codeine.
  • Clinical genotyping to determine CYP2D6 metaboliser status is not widely available. The risk of harm from using codeine should therefore be considered to apply to all patients.
  • Codeine should not be used in:
    • Children aged less than 12 years.
    • Adolescents aged less than 18 years to control pain following surgery to remove tonsils or adenoids, for symptomatic relief of cough, or in those whose respiratory function might be compromised.
    • Women who are breastfeeding.
  • Care is required with all opioid medicines. Children who require an alternative opioid or opioid-like analgesia should be observed in a monitored secondary care environment1.
  • Information on the treatment of pain in children has been published by the WHO, available at www.who.int/medicines/areas/quality_safety/guide_perspainchild/en/.
  • Warn all patients taking opioids to seek immediate medical help if they develop symptoms or signs of opioid toxicity.

Data Summary

Codeine is metabolised (changed) in the liver to the active substances morphine and morphine-6-glucuronide. Metabolism of codeine to morphine mainly involves the Cytochrome P450 enzyme CYP2D6.

Genetic variation in the CYP2D6 gene results in differences between individuals in their ability to metabolise codeine to morphine. Individuals may be classified as a poor, intermediate, extensive or ultra-rapid metabolisers. Patients who are ultra-rapid metabolisers convert codeine to morphine very efficiently, which can lead to morphine toxicity, including respiratory depression and death.

Poor metabolisers are unable to convert codeine to morphine and receive little, if any, analgesic benefit from taking this medicine.

CYP2D6 status is not routinely determined. Therefore, it is not possible to predict who is at risk of opioid toxicity from using codeine, or who will have no benefit.

There is no evidence of efficacy in the medical literature to support the use of codeine in children for pain or for relief of cough. The most recent WHO guidelines for pain management in children do not recommend codeine use2.

Both codeine and morphine are excreted into breast milk. Exposure of the infant to breast milk containing morphine may lead to opioid toxicity in the infant, with the potential for respiratory depression and death. Furthermore, opioid toxicity affecting the mother (such as somnolence) may limit her ability to identify signs of opioid toxicity in her infant, and also her ability to safely care for her baby.

The changes to the approved use of codeine in New Zealand are in line with changes in other countries, including, Australia, the United States, Europe and Canada.

What action is Medsafe taking?

Medsafe is working with sponsors of codeine-containing products to update the data sheets and package labelling to include the revised age restrictions.

Further information

More information on the changes to the age restrictions for codeine in New Zealand was published in Prescriber Update, available at: http://medsafe.govt.nz/profs/PUArticles/June2018/SpotlightOnCodeine.htm

The safety of codeine in children was discussed at the 173rd MARC meeting. The minutes of this meeting are available at: http://medsafe.govt.nz/profs/adverse/Minutes173.htm#3.2.2.

Medsafe’s report on the safety of codeine in children is available at: http://medsafe.govt.nz/committees/MARC/Reports.asp

How to report adverse events

Phone + 64 3 479 7247 to speak to a Medical Assessor at the Centre for Adverse Reactions Monitoring (CARM)
  From your iPhone using the ADR online app
Online Submit a report to CARM
Prescribers can submit using the online reporting tool available in patient management software
Yellow Card A completed Yellow card can be submitted to CARM via email, fax or mail
Email carmnz@otago.ac.nz
Fax +64 3 479 7150


Medsafe cannot give advice about an individual’s medical condition.  If you have any concerns about a medicine you are taking Medsafe encourages you to talk to your healthcare professional.

References
  1. SPANZA Advisory on Tramadol – May 2017: Recommendations Following FDA Warnings about Tramadol Use in Children. Society for Paediatric Anaesthesia in New Zealand and Australia. Available at: www.spanza.org.au/resources-links/guidelines/
  2. World Health Organization, WHO Guidelines on the Pharmacological Treatment of Persisting Pain in Children with Medical Illnesses. 2012, World Health Organization. Available at: www.who.int/medicines/areas/quality_safety/guide_perspainchild/en/