Conclusions: Codeine-related deaths with and without other drug toxicity are increasing as the consumption of codeine-based products increases. Educational messages are needed to better inform the public about the potential harms of chronic codeine use, especially in the context of polypharmacy. Research has found that increased prescribing of opioid analgesics during the past decade has resulted in rises in mortality caused by overdose in many developed countries. It is important to test this assumption, as more codeine is consumed in the United Kingdom, Canada and Australia than any other opioid.
Concerns have been raised in a number of countries about the adverse consequences of codeine use. Use among children has been limited in several countries, and there have been calls to completely remove codeine from the market.
There are documented risks associated with prolonged codeine use. It can produce tolerance, which may lead to escalating doses and dependence, particularly among patients whose pain is not well managed. Prolonged use of high-dose codeine—ibuprofen combinations has been linked with gastrointestinal disease and renal failure, 12 - 14 while paracetamol—codeine combinations have been linked with hepatotoxicity.
There are also concerns about the variability with which codeine is metabolised. Codeine is converted to morphine in the liver by the enzyme cytochrome P 2D6. Codeine-related mortality has increased in a number of countries, including the UK, 18 and case series of codeine deaths have been reported in the United States, 19 the UK and Australia.
Analysis of mortality data provides an opportunity to systematically examine the characteristics of codeine users who experience the most severe adverse consequence, a fatal overdose.
In this article, we present data on codeine-related mortality in Australia, examining:. We searched the National Coronial Information System NCIS for deaths during the period — in which codeine toxicity or overdose was recorded as a direct or a contributory cause of death. The NCIS is a centralised online record of deaths reported to the coroner. The NCIS contains coronial files from all states and territories in Australia and from New Zealand, but this article reviews only deaths in Australia, where routine toxicological screening is conducted after most drug-related deaths.
Findings on the role of particular substances in these deaths are made by a coroner, often on the advice of forensic toxicologists. Keyword searches were also conducted in findings documents, yielding additional cases.
The focus of our study concerned codeine-related deaths, and the methods outlined in Appendix 1 were used to extract cases of interest. Appendix 2 outlines the methods used to distinguish between deaths involving codeine only, and those involving both codeine and morphine. It can be technically difficult to distinguish between deaths caused by codeine, heroin or morphine because of the manner in which these drugs are metabolised.
Codeine is metabolised to morphine, and codeine can also be produced as a metabolite of heroin. Cases were removed from the dataset in which there was clear evidence that heroin had been consumed before death eg, the detection of 6-monacetylmorphine, or eyewitness reports of heroin use , as were those in which there was no evidence of codeine consumption.
Codeine-related deaths were therefore defined as deaths where codeine was detected and codeine toxicity contributed to death, including deaths attributed to multiple drug toxicity. During the period —, we identified a total of deaths in which codeine toxicity was a contributory cause of death. Seven deaths were excluded because, on closer examination, they were not clearly drug-related eg, the cause of death was recorded as gunshot wound, with codeine toxicity as a contributory cause , or because codeine was recorded in the toxicological report but was not considered to be a contributory cause of death.
The remaining cases were included in our analysis. Several variables of interest were not consistently coded in the NCIS because of differing jurisdictional procedures. These included whether the deceased had a recorded history of injecting drug use, chronic pain, mental health problems or substance use problems including misuse and dependence. In addition, where possible, we recorded the brand name of the codeine consumed eg, Panadeine forte, containing mg paracetamol and 30 mg codeine phosphate; Panadeine, containing mg paracetamol and 8 mg codeine phosphate; Nurofen Plus, containing mg ibuprofen and All these variables were coded using information contained in police, autopsy and findings reports.
Numbers of deaths per million population were calculated using Australian Bureau of Statistics estimates of the resident population for 30 June of each year. Differences in the intent characteristics of cases accidental, intentional, not determined were analysed by multinomial logistic regression. We present data on the characteristics of cases as well as on whether the deaths were intentional or accidental for the period — We present trends in codeine-related deaths by intent and as rates per million population for the period — only.
As data for — were likely to be incomplete some cases would not yet have been finalised on the NCIS , trends for the segment — could not be reliably determined. Trends over time were tested using Poisson regression modelling. The outcome variable for the model was intent accidental or intentional.
In order to place codeine-related deaths into the broader context of opioid-related deaths, NCIS data for other opioid-related deaths are also presented here; that is, where heroin, Schedule 8 opioids including buprenorphine, fentanyl, methadone, morphine or oxycodone or multiple opioid toxicity were identified as underlying or contributory causes of death.
Poisson regression modelling indicated that the rate of all codeine-related deaths increased during the period — by 0. The rate of deaths due to accidental codeine overdose also increased significantly, with a 9.
There was no significant trend in intentional codeine overdose deaths during — Deaths attributed to heroin, Schedule 8 opioids, and multiple opioid toxicity were more common than codeine-related deaths Box 2. The rate was highest for heroin- and Schedule 8 opioid-related deaths, at about 16 deaths per million persons for each in Most codeine-related deaths during — , A small proportion , 7.
The remaining deaths 8. The rate of increase in the number of deaths specifically attributed to codeine was greater than the rate of increase in the number of deaths attributed to multiple drug toxicity data not shown. The numbers of codeine-related deaths among men and women were similar, and the mean age at death was 45 years Box 3.
Just under half the deaths , Intent was not determined in the remaining deaths More than half In Where the name or specific details of the codeine product were available, a prescription codeine product most commonly Panadeine forte was recorded in Those who had intentionally overdosed were more likely to be older, female and have a history of mental health problems, and were less likely to have a history of substance use problems, chronic pain or injecting drug use Box 3.
Mental health problems were common in those involved in intentional deaths, and the combination of chronic pain and mental health problems were recorded for A range of other drugs were detected during the toxicological investigation of these deaths. The most common were benzodiazepines Combination codeine products were significantly more likely to be recorded in intentional overdoses It was significantly less likely that pharmaceutical opioids The rate of codeine-related deaths increased significantly between and , from 3.
The increase was primarily driven by an increase in accidental deaths. A potential driver may have been the introduction in Australia of OTC products containing larger amounts of codeine, including codeine combined with ibuprofen. Two distinct populations were detected. Those who had intentionally overdosed were more likely to be older, female and have a history of mental health problems; those who had accidentally overdosed were more likely to have a history of substance use problems, chronic pain and injecting drug use.
These patterns suggest that, in the accidental deaths, there may be evidence of: a codeine being used to top up prescribed pain medication; b dose escalation of codeine; and c the development of codeine dependence. These characteristics highlight a complex patient population in need of specialist services. In cases where data were available, most deaths involved people who had been prescribed codeine products, although a significant minority The investigation of trends in the sales of OTC codeine as well as of codeine prescribing patterns is warranted, and will assist understanding patterns of codeine consumption and related harms in Australia.
Our findings suggest the need for different public health and clinical strategies to prevent fatal intentional and accidental codeine overdoses. Suicide prevention strategies are needed to reduce intentional overdose deaths. A meta-analysis of suicide prevention strategies 24 indicated that educating general practitioners has significantly reduced suicide rates in a number of countries. An increased focus on screening for depression and suicide risk is important when prescribing codeine in primary care encounters, which represent an important opportunity for interventions that reduce the risk of suicide.
It may not be enough to change codeine prescribing practices, given that codeine is available over the counter in Australia. Pharmacists may have an important role to play in minimising harms 6 by advising consumers who purchase codeine products about the risks of chronic use and by encouraging them to seek further medical advice. It is more challenging to reduce accidental codeine overdoses, which are more prevalent and increasing in number.
The high prevalence of substance use problems among those who had accidentally overdosed suggests the need for general practitioners to screen for substance misuse history when prescribing codeine.
Patient education is also essential. This makes now a timely moment to consider some of the wider measures that GPs can take to improve patient outcomes and avoid the over-prescription of some medications. Naloxone nasal spray is a fast-acting opioid antagonist now PBS-listed for use in the community. Find out more. The Australian Government is investing in a pilot program to make naloxone available free to people who may experience, or witness, an opioid overdose. Opioids have made headlines recently with a number of cities and counties across North America taking legal action against drugmakers and distributors in federal courts for the widespread damages caused by opioid addiction.
Read more on Ausmed Education website. Opioid medicines for chronic pain continue to pose a challenge in primary health care. Healthdirect Australia is not responsible for the content and advertising on the external website you are now entering. There is a total of 5 error s on this form, details are below. Please enter your name Please enter your email Your email is invalid.
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Send to: is required Error: This is required Error: Not a valid value. What is an accidental overdose of medicine? How can it happen? You are more at risk of accidental overdose if one or more of the following applies to you: You are taking a combination of different medicines.
You don't follow the instructions of your doctor or pharmacist properly. You take more than one medicine with the same active ingredient for example, 2 cold and flu medicines might have different brand names but contain the same active ingredient, meaning you will take double the dose. The medicine is stronger than you thought medicines with the same brand name come in different strengths, so it's always important to read the label, even if you have taken the medicine before.
You use the wrong measuring device for the medicine, such as a tablespoon rather than a teaspoon. You forget how much medicine you've already taken. You mix medicine with alcohol.
You don't calculate a child's dosage based on the child's weight correctly. You didn't store a medicine safely and a child accidentally swallowed or drank it.
Symptoms of overdose of medicine The symptoms of a medicine overdose depend on the type of medicine. Call triple zero and ask for an ambulance if someone: is not breathing, or their breathing is shallow is snoring or gurgling has blue lips or fingertips has floppy arms and legs appears to be unresponsive appears to be disorientated can't be woken up Take extra care with these medicines Opioids The most common cause of fatal accidental overdoses in Australia is opioids , such as the strong painkillers oxycodone and fentanyl.
Access to overdose-reversing medication Naloxone is a medicine that can reverse the effects of an opioid overdose. The health care provider will measure and monitor the person's vital signs, including temperature, pulse, breathing rate, and blood pressure. Codeine is usually combined with other medicines, such as acetaminophen.
Because of this, the harmful effects of these other medicines must also be treated. Shock, severe pneumonia, brain damage, and death are possible. Aronson JK. Opioid receptor agonists. In: Aronson JK, ed. Meyler's Side Effects of Drugs. Waltham, MA: Elsevier; Philadelphia, PA: Elsevier; chap Reviewed by: Jacob L.
Editorial team.
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