Codeine-related deaths: a cause for concern

Published in Health News and Evidence

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Practice points | Codeine-related deaths more than double in 10 years | Implications for practice | Potential rescheduling of codeine | References

Summary

A new Australian study has investigated codeine-related deaths over a 10-year period. The analysis has shown some worrying trends, with deaths related to codeine use doubling over the study period. Analysis of the characteristics of people who died from codeine-related overdose suggests a complex population of patients who require careful management by prescribers and pharmacists.

Key points

  • Codeine-related deaths have doubled between 2000 and 2009
    Continued vigilance is required to help minimise harm from codeine use.
  • Pharmacists have an important role to play in minimising harm
    As codeine is available over the counter, pharmacists are an important source of information and advice for consumers.
  • Consumer education is essential
    All health professionals should endeavour to inform consumers about the safe use of codeine and preparations containing codeine, including the dangers associated with combining medicines.

Codeine-related deaths more than double in 10 years

An Australian study examining codeine-related mortality in a 10-year period from 2000 to 2009 found that deaths where codeine was determined to be an underlying cause had more than doubled from 3.5 per million to 8.7 per million.1 This is about half the number of deaths related to Schedule 8 drugs and heroin.1

Accidental overdose was more common than intentional death (48.8% compared to 34.7%) and almost all deaths involved mixed drug toxicity (83.7%).1 People who died from accidental overdose were more likely to have also taken benzodiazepines, pharmaceutical opioids and illicit substances than those who died from intentional overdose.1 They were also more likely to have a history of substance use problems, injecting drug use and chronic pain.1

People who died from intentional overdose were more likely to have taken paracetamol, ibuprofen and/or doxylamine. They were also more likely to be older, female and have a history of mental health issues.1

The patterns of concomitant drug use and of comorbid conditions found in this study suggest that people who died from accidental overdose may have been using codeine in addition to prescribed pain medicines, engaging in dose escalation of codeine and developing codeine dependence.1

Implications for practice

Where data were available, more than half of codeine-related deaths involved people who were prescribed codeine.1 However 40% of people had used over-the- counter products and this suggests a serious issue for clinical practice that involves both prescribers and pharmacists.1

The numbers of patients who died from intentional overdose in this study suggests that prescribers should consider screening for depression and suicide risk prior to prescribing codeine. The high prevalence of substance use problems in patients who died from accidental overdose suggests that prescribers need to consider the risk of substance misuse before prescribing codeine, as is recommended for prescribing Schedule 8 substances.2

Prescribers need to be aware that codeine metabolism is dependent on the activity of cytochrome P450 2D6. Genetic variation in this enzyme produces some individuals (about 1%–2% of the white population) who are classed as ultrarapid metabolisers and have a greater risk of adverse events such as respiratory depression and fatal overdose due to the greater conversion of codeine to morphine.1,3 Conversely, poor metabolisers (about 5%–10% of the white population) have little codeine converted to morphine and therefore receive little analgesic benefit.1,3

Patient education is essential whether codeine is prescribed or dispensed over the counter. Pharmacists play a key role ensuring patients understand the potential dangers of codeine, particularly when taken in combination with other medicines (ie benzodiazepines or opioids). Patients also need to understand the harms associated with combination products, such as paracetamol–codeine combinations or cold and flu medicines.

Potential rescheduling of codeine

The Therapeutic Goods Administration (TGA) has published a proposal to recommend that all over-the-counter medicines containing codeine be rescheduled as prescription-only medicines. The final decision will not be made until late November 2015.4

References
  1. Roxburgh A, Hall WD, Burns L, et al. Trends and characteristics of accidental and intentional codeine overdose deaths in Australia. Med J Aust 2015;203:299. [PubMed].
  2. Expert Group for Analgesics. Therapeutic Guidelines: Analgesic Version 6. Therapeutic Guidelines Ltd, 2012 [TG online] (accessed 8 October 2015).
  3. Crews KR, Gaedigk A, Dunnenberger HM, et al. Clinical Pharmacogenetics Implementation Consortium guidelines for cytochrome P450 2D6 genotype and codeine therapy: 2014 update. Clin Pharmacol Ther 2014;95:376-82. [PubMed].
  4. Therapeutic Goods Administration. Proposal for the re-scheduling of Codeine products. Canberra: Department of Health, 2015. [Online] (accessed 8 October 2015).