The European Medicines Agency’s Pharmacovigilance Risk Assessment Committee (PRAC) has recently recommended restrictions on the use of codeine-containing medicines for cough and cold in children because of the risk of serious side effects

The European Medicines Agency’s Pharmacovigilance Risk Assessment Committee (PRAC) has recently recommended restrictions on the use of codeine-containing medicines for cough and cold in children because of the risk of serious side effects

Last Updated on March 22, 2015 by Joseph Gut – thasso

March 21, 2015 – The European Medicines Agency’s Pharmacovigilance Risk Assessment Committee (PRAChas recently recommended restrictions on the use of codeine-containing medicines for cough and cold in children because of the risk of serious side effects with these medicines, including the risk of breathing problems.

The PRAC recommended specifically that:

  • Codeine should be contraindicated in children below 12 years. This means it must not be used in this patient group.
  • Use of codeine for cough and cold is not recommended in children and adolescents between 12 and 18 years who have problems with breathing.
  • All liquid codeine medicines should be available in child-resistant containers to avoid accidental ingestion.
CYP2D6-dependent metabolic conversion of Codeine to Morphine
CYP2D6-dependent metabolic conversion of Codeine to Morphine

The effects of codeine are due to its conversion into morphine in the body. Some people convert codeine to morphine at a faster rate than normal, resulting in high levels of morphine in their blood. High levels of morphine can lead to serious effects, such as breathing difficulties. An earlier post by thasso addressed this problem from the side of genetic predisposition of some people (including children)  for very high conversion rates of codeine to morphine, which may lead to death in some serious cases, e.g.. in children who are phenotypically members of the CYP2D6 Ultrametabolizer Patient Subgroup based on their CYP2D6 genetic background because of fatal respiratory depression based on unusual (fatal) high exposure to morphine. The occurrence of the CYP2D6 Ultrametabolizer Phenotype will vary widely in children from different ethnic group origins in that the allele responsible for the CYP2D6 Ultrametabolizer Phenotype is present in approximately 30% of people of African (Ethiopian/Eritrean) descent and only at roughly 1% in people of Northern European descent.

Here, the PRAC considered that, although morphine-induced side effects may occur in patients of all ages, the way codeine is converted into morphine in children below 12 years is variable and unpredictable, making this population at special risk of such side effects. In addition, children who already have problems with their breathing may be more susceptible to respiratory problems due to codeine. The PRAC also noted that cough and cold are generally self-limiting conditions and the evidence that codeine is effective at treating cough is limited in children. The PRAC further recommended that codeine must not be used in people of any age who are known to convert codeine into morphine at a faster rate than normal (‘ultra-rapid metabolisers’) nor in breastfeeding mothers, because codeine can pass to the baby through breast milk.

During its review, the PRAC consulted EMA’s Paediatric Committee as well as healthcare professionals’ organisations. The review was triggered by a previous review of codeine for pain relief in children, which resulted in several restrictions being introduced in order to ensure that only children for whom the benefits are greater than the risks are given the medicine for pain relief. As the reasons for these restrictions could also apply to the use of codeine for cough and cold in children, an EU-wide review of such use was initiated. The restrictions the PRAC has now recommended for codeine for cough and cold are largely in line with the previous recommendations for codeine when used for pain relief. The PRAC recommendations will now be sent the Co-ordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh), which will adopt a final position and provide guidance to patients and healthcare professionals. In the meantime, patients or their carers should speak to their doctor or pharmacist if they have any questions or concerns.

More about the medicine

Codeine is an opioid medicine that is converted into morphine in the body. It is widely used for pain relief and for the treatment of the symptoms of coughs and colds. In the EU, codeine-containing medicines have been approved via national procedures, and are available either on prescription or over the counter in the different Member States. Codeine is marketed as a single-ingredient medicine or in combination with other active substances.

Ph.D.; Professor in Pharmacology and Toxicology. Senior expert in theragenomic and personalized medicine and individualized drug safety. Senior expert in pharmaco- and toxicogenetics. Senior expert in human safety of drugs, chemicals, environmental pollutants, and dietary ingredients.

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