Issue 38 / 5 October 2015

PRODUCTS that combine codeine with other analgesics should not be available over the counter, according to a leading addiction medicine expert who says the drugs pose a significant public health risk.
Associate Professor Michael McDonough, medical director of the Addiction Medicine and Toxicology Service, Western Health, in Melbourne, was responding to MJA research that showed the rate of codeine-related deaths had increased from 3.5 per million in 2000 to 8.7 per million in 2009. (1)
The study of codeine-related deaths found those attributed to accidental overdose (48.8%) were more common than intentional deaths (34.7%), and that 83.7% of the deaths resulted from multiple drug toxicity. The researchers wrote that where the name or specific details of the codeine product were available, a prescription codeine product (most commonly Panadeine forte) was recorded in 343 of 572 cases and over-the-counter (OTC) products in the remaining 229 cases.
Dr McDonough told MJA InSight the increase in deaths represented “a huge jump”, yet the study didn’t include additional “downstream deaths” due to gastrointestinal disease and renal failure caused by analgesics combined with codeine.
The Therapeutic Goods Administration has proposed that codeine products be rescheduled from Schedule3 to Schedule4 due to potential issues of morbidity, toxicity and dependence. (2)
“I’d say emphatically that codeine should not be available over the counter. If people need an opioid analgesic they should have a medical assessment [first]”, Dr McDonough said.
“It needs to be said that opioids kill more people in our country than ice [crystalline methamphetamine] does, by a long shot. How our society and regulators appraise the risk of codeine needs to be revisited and we need to question the safety of over-the-counter availability of codeine and, particularly, the safety of combination analgesic products that contain codeine.”
Dr McDonough said the basic therapeutics of combination preparations that contained codeine were unsound. If doctors recommended patients take a combination drug, the doctor and the patient did not know which one was helping.
He said he was disappointed by the researchers’ conclusion that the public needs more education about the potential harms of chronic codeine use, saying what was needed was “more resolute action”.
Dr McDonough said he had seen evidence through his own practice of how secretive misusers of analgesics could be, and that vulnerable people were difficult to detect clinically because they weren’t volunteering their regular heavy use of OTC analgesics.
Michelle Lynch, acting national vice president of the Pharmaceutical Society of Australia (PSA), said the increase in codeine overdose deaths revealed by the MJA study was alarming and served as a strong call for action.
However, Ms Lynch said preventing OTC sales of products that combined codeine with analgesics was not appropriate as it would disadvantage many people who find the drugs beneficial.
She said people who became dependent on OTC analgesics containing codeine bought 100-tablet packs, so tracking the frequency of purchases was crucial. A national prescription monitoring system to track prescription and OTC medication purchases in real-time was needed to identify at-risk patients. 
While the federal government’s Electronic Recording and Reporting of Controlled Drugs initiative was a step in the right direction, implementation across Australia has been slow. (3)
Ms Lynch said the PSA recognised the codeine-related death rate was a critical issue and developed resources to help pharmacists discuss appropriate pain management solutions with patients, including issuing warning stickers that say: “For 3 days use only — can cause addiction”.
Dr Simon Holliday, chair of the RACGP’s National Faculty of Specific Interests pain management network, said there was a potential conflict of interest at play in relying on pharmacists to educate patients about the dangers of codeine.
He said it was also difficult for pharmacists to assess mental health, past substance misuse and history of depression or suicidality.
Dr Holliday agreed that real-time prescription monitoring was crucial, saying it had been successful in Tasmania, but privacy issues meant it hadn’t been rolled out nationally at this stage.
“In Tasmania [where monitoring has been introduced] it takes 6 seconds to see if someone has seen every other doctor or pharmacist in town. It is the equivalent of seatbelts on our road system, but it won’t pick up all the different harms coming from opiates. For example, it won’t detect harm in people with sleep apnoea who take their dose as prescribed”, Dr Holliday said.
(Photo: Di Studio / shutterstock)

8 thoughts on “Codeine deaths need action

  1. Anonymous says:

    As the mother of a codeine addict of 5 years, please do make this prescription only. My son dissolves then filters out paracetamol from over the counter tablets using 20+ each time, he’s crashed his car multiple times, mounted pavements and ran into other motorists, its only a question of time before someone is badly hurt. He drinks whole bottles of cough mixture, J Collis Brown is a typical example. Wrote to my MP and minister, they don’t see a problem, but I see teenagers getting high on filtered tablets and cough mixture something well known n schools bought legally over the counter, it ruins lives. There is an online petition to 10 Downing Street, please sign it.

  2. Dr Yolande Lucire says:

    Testing for CYP450 2D6 would save millions of dollars in costs for useless prescriptions. Certainly morphine, (Sub 2D6, mainly 3A4) pethidine (Sub 2B6, Sub 2C19, Sub Ind 3A4) and even diamorphine (heroin) which is not metabolised by the cytochrome P450 system) could be made available to persons who get no benefit from codeine and have severe intractable pain. There remain risks of overdose or addiction. As a person (2D6*1*4) who stopped breathing in a recovery room following 100 mg pethidine IV, I have a healthy respect for risks and as yet no idea of the status of my CYP 3A4 where over 20% of Caucasians are deficient. The pharmacogentics of pain control should be a priority for the introduction of personalized medicine education which is now being, funded albeit slowly, by Commonwealth Health.

  3. Sue Ieraci says:

    Dr Lucire’s comment would suggest that, if oral morphine is available, appropriate and effective, it;s a much “cleaner” solution, since codeine requires metabolism to morphine anyway.

  4. Dr. Yolande Lucire says:

    Genetic testing for Cytochrome P450 2D6 could reduce the prescribing of codeine, tramadol, hydrocodone & oxycodone to a population of whom 10% have no CYP2D6. Ultrarapid Metabolisers (UMs) at 2D6 comprise 3% of the population & they convert opioid prodrugs to morphine too fast. UMs die or commit suicide at 15 times the rate of PMs. Other drugs are also involved in these deaths.

    Also at risk of death are people co-prescribed drugs that inhibit cytochrome P450 2D6; antidepressants, antipsychotics, cimetidine, dextropropoxephene & methadone.

    A 21-year-old hospitalized for akathisia, suicidality & violence was given sertraline 600 mg/day, morphine 15 mg/day, oxycodone 40 mg/day, temazepam 10 mg/day diazepam 20 mg/day, ibuprofen 400 mg/day, baclofen 40 mg/day & orphenidine 200 mg/day. Sertraline was reduced to 200 mg/day. On the sixth day he stopped breathing for eight minutes.

    His genotype was normal, 2D6*1*2, 2C9*1*1, 2C19*1*17. The concurrent use of sertraline, an inhibitor of CYP2D6, had rendered the opioids ineffective. Removal of sertraline was the cause of toxicity.

    This case resembled the death of Heath Ledger who, according to the press reports, had stopped taking sertraline three days earlier. The New York City Medical Examiner’s Office reported: “Mr Heath Ledger died as a result of acute intoxication by the combined effects of oxycodone, hydrocodone, diazepam, temazepam alprazolam and doxylamine. We have concluded the manner of death is accident resulting from abuse of prescription medications.”

    Doctors need to consider the effects of concurrent medications and recent removal of CYP 2D6 inhibitors when prescribing.



  5. Sue Ieraci says:

    The comments so far are surprising. It has long been known that 8mg of codeine is subtherapeutic. To get an effective dose with OTC preprarations, you get too much of the co-ingestant (paracetamol or ibuprofen). SO, it’s good practice to get rid of the placebo level of codeine (which contributes to side effects) and use either paracetamol/NSAID alone for mild to moderate pain, and therapeutic-dose presecribed analgesic for more severe pain. Since 10% of the population don’t metabolise codeine to the active morphine, and oral morphine is available, codeine may have less of a place in future. That’s rational improvement, isn’t it?

  6. Dr Louis Fenelon says:

    Notwithstanding all the well reported issues resulting from narcotic addiction, I am not sure how URGENT action is indicated because of a change affecting 0.005% of the population?  It is the duty of our profession to address our skills where needed most urgently – triage.  in this case triage suggests pharmacists are more than capable of managing combination analgesics and doctors have far more important things to do.

    Aside from failing to understand in any logical, clinical way how combinations of analgesics including codeine, taken at doses below the upper end of the therapeutic range have become a risk after such a long period of safe use, what I really don’t understand is how proving something makes it deserving of urgent attention and remedy?  Maybe this isn’t as outstandingly stupid as making people eat artificial instead of real food on the basis of research, but it’s close.  Removing access to effective analgesics without proposing a valid alternative is a recipe for trouble.  You don’t need research to know that, just common sense.

  7. Peter Ritchie says:

    The term “codeine-related deaths” is alarmist and misleading. Much of the harm is related to the other drugs in the combination e.g. paracetamol taken in overdose, chronic use of ibuprofen, other drugs taken in combination overdose e.g. benzodiazepines and alcohol. In most people the combination of paracetamol and codeine is an effective, simple analgesic. Restricting the use of paracetamol-codeine combinations will lead to millions more GP and Emergency Department presentations for prescriptions for these or other (more addictive) analgesics. Restricting the availability of the toxic NSAID ibuprofen which has been sold over the past 10-15 years increasingly as a “harmless” analgesic would be far more useful and result in less gastrointestinal and renal complications. Restricting codeine will simply make people seek analgesia in other ways. Addicts may even turn to “harder” drugs such as oxycodone (legally) or heroin (illegally). 

  8. Communicable Disease Control Directorate says:

    The incidence of codeine related deaths remains very low despite the “huge jump” and the majority, or at least a substantial proportion, are related to the already Schedule 4 Paracetamol-codeine 500mg/30mg combination. There are legitimate concerns re codiene use and abuse, particularly in combination with ibuprofen but the call for rescheduling is heavy handed to say the least, particularly when there is no evidence presented that rescheduling, to prescription only, works.

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