Some thoughts on the proposed rescheduling of OTC Codeine-containing products to Prescription Only, by Professor Peter Carroll

In the current debate regarding the proposed rescheduling of over the counter (OTC) codeine-containing products to prescription only I believe some individuals and some organisations have made claims which are emotive and erroneous

Below I have tried to address some of these claims from a scientific and clinical perspective

  1. CLAIM: The amount of codeine in OTC codeine-containing analgesics is not efficacious

An Australian study has reported that 1000mg paracetamol combined with 30mg codeine phosphate (equivalent to two Prodeine-15 caplets or two Panadeine Extra caplets) produced significantly greater analgesia than 1000mg paracetamol alone (equivalent to two Panamax or two Panadol tablets) 1

It has also been reported that 20mg codeine base combined with 400mg ibuprofen (equivalent to 2 Nurofen Plus tablets) produced significantly greater analgesia than 400mg ibuprofen alone (equivalent to two Nurofen tablets) 2

Both Panadeine Extra and Nurofen Plus, along with other brands containing the same ingredients in the same strengths, are available as OTC Schedule 3 medicines and these combination products have been reported to produce significantly greater pain relief that either paracetamol alone or ibuprofen alone.

I therefore believe it is incorrect to claim that the amount of codeine in OTC codeine-containing analgesics is not efficacious as it is not supported by the evidence

  1. CLAIM: Making all codeine-containing products prescription only will just bring Australia into line with other countries

At present codeine-containing products are available OTC through pharmacies in comparable countries to Australia such as New Zealand and the United Kingdom. In addition, many countries do not have the equivalent of our S2 and S3 pharmacy schedules so it is not possible in these countries to have lower dose codeine products sold only in pharmacies

To claim that Australia is out of step with other countries regarding the scheduling of codeine is inaccurate, and does not tell the full story

  1. CLAIM: Codeine is causing many deaths in the Australian community

 It has also been reported that during the period from 2000 to 2013 there were 1444 deaths in Australia where codeine toxicity was thought to be a contributing cause, with only 113 deaths being attributed specifically to codeine toxicity over the 13 year period 3

This study also reported that the vast majority of deaths were due to intentional or accidental overdose, and in the cases where the codeine product could be identified, the majority involved a prescription codeine product 3

In addition, the evidence relating to opioid misuse and death concludes that prescription opioids are contributing mostly to the problem 4

I believe any claim that codeine is a major cause of drug death in Australia is not supported by the evidence, and is untrue

  1. CLAIM: Making all codeine-containing products prescription only will reduce codeine use

Department of Health data for the 12 months to June 2017 show that when medical practitioners have the option to prescribe paracetamol combined with either 30mg, 15mg or 8mg of codeine for patients under the Repatriation Benefits Scheme, over 90% of prescriptions are written for a 30mg codeine product 5

In addition, in 2015-2016 there were over 3.7 million prescriptions written in Australia for products containing 30mg codeine and 500mg paracetamol 6

It thus seems reasonable to suggest that if people who are currently using a lower dose OTC codeine-containing product for the short-term treatment of acute pain are forced to visit a GP, they may potentially receive a prescription for a higher strength codeine product. This of course will not reduce codeine use, but actually increase it

It has also been reported that most opioid use in Australia is from prescription products, with OTC codeine products accounting for only 6% of total opioid use 7

  1. CLAIM: An OTC combination product containing ibuprofen and paracetamol would fill any gap left by the unavailability of OTC codeine-containing analgesics

There are many people in the Australian community who should not take nonsteroidal anti-inflammatory agents (NSAIDS) such as ibuprofen, or only take them with caution and monitoring. Examples include

  • It is estimated that around 10% of the Australian population suffer from asthma 8. It has also been reported that 10-20% of adult patients who suffer from asthma also have what is called Aspirin Sensitive Asthma 9,10. If people with Aspirin Sensitive Asthma take an NSAID such as ibuprofen they may experience a worsening of their asthma symptoms, and potentially an acute asthmatic attack. If one uses the lower figure of 10%, it can be estimated from Australian Bureau of Statistics and population data 11,12 that there are around 190,000 adult Australians with Aspirin Sensitive Asthma, and these people should avoid taking an analgesic combination containing ibuprofen
  • In addition, using PBS data 13 for the year ending June 2017 it can be reasonably estimated that there are many hundreds and hundreds of thousands of Australian adults who are taking medications which may potentially have serious drug interaction with ibuprofen. These include
  • Selective Serotonin Reuptake Inhibitors (SSRIs) such as fluoxetine, paroxetine and sertraline used for the treatment of depression 14,15,16,17
  • Warfarin or other anticoagulant medications used to prevent blood clots 17
  • Angiotensin converting enzyme inhibitors (or an angiotensin 2 receptor antagonists) plus a diuretic used for the treatment of high blood pressure or heart failure 17,18,19
  • Hundreds of thousands of Australian adults also take low dose aspirin for cardiovascular protection and ibuprofen, when taken with low dose aspirin, has been reported to reduce the cardiovascular protective effect 17,20
  • Many adults with gastrointestinal disorders such as Crohn’s disease, and those with renal impairment should also only take ibuprofen with caution and monitoring, if at all 21

I therefore believe there are at least 500,000, and possibly up to 1 million Australian adults who should either not take ibuprofen at all, or take it only with caution and monitoring. Codeine and paracetamol combination medications are used by many of these people, and to suggest that they can simply just switch to an ibuprofen and paracetamol combination is not just incorrect, it could lead to serious adverse health outcomes for these people

  1. CLAIM: Some people metabolise codeine rapidly and are at risk of serious adverse effects and toxicity if they take codeine

It has been claimed that between 4-10% of the population are ultra-rapid metabolisers of codeine (they have increased activity of the enzyme CYP 2D6), and if these people take “usual” doses of codeine they are at risk of serious adverse effects and life threatening toxicity which may be fatal due to the increased conversion of codeine to morphine 22

In 2015-2016 there were over 3.7 million prescriptions written in Australia for products containing 30mg codeine and 500mg paracetamol 6. In addition, in that 12-month period many hundreds of thousands, if not millions of Australians would have taken an OTC codeine-containing product. If 4-10% of these people were at risk of life threatening toxicity it seems to me that in the 12-month period there would have been many thousands of hospital admissions due to codeine toxicity, and constant reports of codeine induced toxicity and death

During the period from 2000 to 2013 there were 1444 deaths in Australia where codeine toxicity was thought to be a contributing cause, with only 113 deaths being attributed specifically to codeine toxicity 3. It has also been reported that no severe adverse effects were seen in people who were ultra-rapid metabolisers when they were given a 30mg dose of codeine 23

It thus seems that any claim suggesting that codeine can cause life-threatening toxicity in up to 4-10% of the population is a gross over exaggeration, and is not supported by the scientific or medical literature

To suggest that a patient who might convert more codeine to morphine and be at risk of adverse effects would somehow be protected if the codeine was prescribed by a doctor rather than being recommended by a pharmacist seems totally illogical

  1. CLAIM: OTC codeine-containing analgesics are being used primarily to treat chronic pain

OTC codeine-containing analgesics are indicated for the short term treatment of acute pain, and should not be used for the long term treatment of chronic pain

Although it has been claimed by some that many people are using OTC codeine-containing products inappropriately for the treatment of chronic pain, it has been reported by the Pharmacy Guild that MedsASSIST real time purchase data has shown that of the people using OTC codeine-containing products, 98% were using them as intended 24

MedsASSIST data also shows that some consumers purchase more than one pack over time, and it has been suggested that anyone purchasing a product more than three times over a seven month period is likely to be dependent on codeine 22. There is no evidence to support this claim, and a far more likely explanation is that some consumers suffer from pain states such period pain and migraine on a regular basis and thus need to purchase the products to treat these as they occur

I believe there is no evidence to support the claim that many consumers are using OTC codeine-containing products to treat chronic pain. If codeine is being used to treat chronic pain it is far more likely to be as a result of the 3.7 million prescriptions written over 12 months for products containing 30mg codeine and 500mg paracetamol 6

Peter Carroll is Professor and Head of Pharmacology, School of Medicine, University of Notre Dame, Sydney; Honorary Professor, Discipline of Pharmacology, University of Sydney; President, NSW Branch of the Pharmaceutical Society of Australia

References

  1. Macleod AG et al (2002) Australian Dental Journal 47(2),147-151
  2. McQuay H.J et al (1989) Pain, 37, 7-13
  3. Roxburgh A et al (2015) Medical Journal of Australia 203(7), 299e1-299e7
  4. Australia’s Annual Overdose Report, A Penington Institute Report, April 2017
  5. PBS data July 2016 to June 2017 ly/2fdqfEJ 
  6. https://www.pbs.gov.au/statistics/expenditure-prescriptions/2015-2016/exp-prs-2015-16-table-13.pdf
  7. Gisev N et al (2017) Pharmacoepidemiol Drug Saf. October, 1–https://doi.org/10.1002/pds.4329
  1. asthmaaustralia.org.au/national/about-asthma/what-is-asthma/statistics
  2. Jenkins C et al (2004) British Medical Journal328, 434-440
  3. Vally H et al (2002) Thorax 57,569-574
  4. abs.gov.au/AUSSTATS/abs@.nsf/mf/3101.0
  5. info/en/Australia#population_2017
  6. humanservices.gov.au/statistics/pbs_item.jsp
  7. Horne JR & Hansten PD (2003) Drug Interactions: Insights and Observations Special Senior Edition December 2003. hanstenandhorn.com/hh-article12-03.pdf
  8. de Jong JCF et al (2003) Br J Clin Pharmacol 55, 591-599 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1884264/pdf/bcp0055-0591.pdf
  9. Loke YK et al (2007) Aliment Pharmacol Ther 27, 31-40
  10. eMIMS Drug Interactions and TGA Approved Product Information, eMIMS June 2017
  11. tga.gov.au/publication-issue/australian-adverse-drug-reactions-bulletin-vol-25-no-5#a1
  12. Thomas M (2000) MJA172, 184-185
  13. pharmacytimes.com/publications/issue/2013/may2013/antiplatelet-effects-of-aspirin-which-nsaids-interact
  14. TGA approved product information for Nurofen Plus, eMIMS June 2017
  15. Department of Health, Therapeutic Goods Association. Final decisions and reasons for decisions by delegates of the Secretary to the Department of Health, dated 25 January 2017
  16. Kirchheiner J (2007) The Pharmacogenomics Journal 7 (4), 257-265.
  17. https://ajp.com.au/news/silly-decision-wont-curb-codeine-misuse/