The Canadian Medical Association (CMA) is pleased to provide comment on the proposal by Health Canada1 to revise the listing for naloxone on the Prescription Drug List (PDL) to allow the non-prescription use of naloxone, "when indicated for emergency use for opioid overdose outside hospital settings".
The CMA has over 83,000 physician-members. Its mission is helping physicians care for patients and its vision is to be the leader in engaging and serving physicians, and the national voice for the highest standards for health and health care.
The harms associated with opioids, which include prescription medicines such as oxycodone, hydromorphone and fentanyl, as well as illegal drugs such as heroin, is a significant public health and patient safety issue. Harms include addiction, diversion, overdose and death.
According to 2013 estimates2, Canada has one of the highest per capita consumptions of prescription opioids in the world. In North America, about 5% of the adult population, and substantially higher rates for teens and young adults, reported non-medical opioid use in the previous year. This rate is higher than all other illegal drugs, with the exception of marijuana.3
Data on the harms caused by opioids are not collected systematically in Canada; however, practitioners have seen the significant impact of these drugs on their patients and to whole communities, including indigenous peoples. Opioid addiction rates from 43% to 85% have been reported in some indigenous communities.4 5 In Ontario, according to the Office of the Chief Coroner, opioid-related deaths nearly tripled from 2002 to 2010.6
Canada's physicians believe that Canada needs a comprehensive national strategy to address the harms associated with psychoactive drugs, whether illegal or prescription-based.7 One component of this strategy is the prevention of overdose deaths and complications with appropriate medication and prompt emergency response.
For over four decades, naloxone (or Narcan(r)) has been used as a prescription drug for the complete or partial reversal of opioid overdoses. Naloxone counteracts the life-threatening depression of the central nervous system and respiratory system, allowing an overdose victim to breathe normally. The World Health Organization placed naloxone on its list of essential medications in 1983.
Physicians have been encouraged to identify patients who could benefit from the co-prescription of naloxone, along with opioids, when these are necessary. Increased risk for opioid overdose includes previous episodes of overdose, history of substance use disorder, higher opioid dosages, or concurrent benzodiazepine use.8 9
More recently, with the increase in opioid overdoses, different provinces have created programs to increase access to naloxone outside of health care settings, such as "take-home naloxone programs". The experience in Canada and in other countries has been shown to have various benefits, including reducing overdose deaths.10 11 In Canada, naloxone has been administered through intramuscular or subcutaneous injection in these community-based programs, but in other countries it has also been available in a nasal spray form or in a pre-filled auto-injector format. Those that receive the naloxone kit are trained in the recognition of signs and symptoms of opioid overdose, in the administration of naloxone and first aid and in the need to call for medical follow-up.
In its 2015 policy on Harms associated with Opioids and other Psychoactive Prescription Drugs, the CMA supports the improvement of access to naloxone, particularly by individuals who are at a high risk of overdose as well as third parties who can assist a person experiencing an opiate-related overdose. The CMA also encourages the creation and scaling up of community-based programs that offer access to naloxone and other opioid overdose prevention tools and services. This would include training for health workers, first responders, as well as opioid users, families and peers about the prevention of overdose fatalities.12 Also in 2015, the CMA approved a resolution supporting "the development and implementation of a national strategy on the use of naloxone".13
A report issued by the United Nations Office on Drugs and Crime and the World Health Organization supports making naloxone available to first responders as well as to people dependent on opioids, their peers and family members who are likely to be present when an overdose occurs.14 Many other organizations, such as the Canadian Pharmacists Association, the American Medical Association and the American Public Health Association, are also supportive of enhanced access to naloxone in the community.15 16 17
The prescription status has been one of the barriers to increased access to naloxone. It is more likely that a family member, partner or friend would need to administer the naloxone in an overdose than the person who is prescribed the drug. Community-based programs have had to work with standing orders from prescribers. First responders, such as police officers and firefighters, should be able to carry and administer the drug, given they are often the first professionals to arrive at a scene where someone has overdosed.
According to Health Canada, the provinces and territories have collectively asked that the prescription status be re-evaluated. Health Canada has undertaken a Benefit-Harm-Uncertainty assessment of naloxone, and come to the following conclusions:
This assessment recommended that naloxone could safely be administered without the direct supervision of a physician if the person administering the drug has appropriate training.
The main risks associated with the unsupervised use of the drug are:
* the administrator may have difficulty filling the syringe and administering the drug under pressure in an emergency situation;
* the administrator may not seek professional care for follow-up of the patient after injection;
* chance of the patient relapsing since the effects of naloxone may only last for up to one hour depending on amount and type of opioid causing the overdose;
* that the patient may become very agitated and aggressive after coming out of the opioid depression (Acute Opioid Withdrawal Syndrome).
These risks can be mitigated with appropriate training of the potential administrator before naloxone is distributed. The benefit of quickly responding to an overdose far outweighed these risks. Evidence from provincial take-home programs indicates that naloxone can be administered (intramuscularly or subcutaneously) by a layperson and its effects monitored successfully without practitioner supervision. Although an opioid overdose might be mistakenly diagnosed by a layperson, the injection of naloxone in a person not overdosing on an opioid will cause no serious harm.18
Various jurisdictions have delisted or are studying special conditions for the status of naloxone as a prescription drug, including Italy and some U.S. States.19
The CMA appreciates the opportunity to provide feedback on this important matter to physicians, and congratulates Health Canada in taking the initiative to make naloxone more accessible in the community; thereby helping to address the concerning levels of opioid overdoses in Canada.
That Health Canada proceed with the revisions to the listing for naloxone on the Prescription Drug List, to allow the non-prescription use of naloxone when indicated for emergency use for opioid overdose outside hospital settings. As outlined in Health Canada's assessment, the potential risks can be mitigated by well-designed community-based programs.
That Health Canada assess the option of licensing naloxone products that don't require training for intramuscular or subcutaneous injection, such as nasal sprays or automated handheld injectors (similar to epinephrine auto-injectors for use in serious allergic reactions), in order to further increase accessibility.
1 Health Canada. Consultation on the Prescription Drug List: Naloxone. File number: 16-100479-342. January 14 2016. Ottawa. Available: http://www.hc-sc.gc.ca/dhp-mps/consultation/drug-medic/pdl_ldo_consult_naloxone-eng.php (accessed 2016 March 17).
2 International Narcotics Control Board. Narcotics drugs: estimated world requirements for 2013; statistics for 2011. New York: United Nations; 2013. Available: https://www.incb.org/documents/Narcotic-Drugs/Technical-Publications/2012/NDR_2012_Annex_2_EFS.pdf (accessed 2016 March 17).
3 Fischer B, Keates A, Buhringer G, et al. Non-medical use of prescription opioids and prescription opioid-related harms: why so markedly higher in North America compared to the rest of the world? Addiction. 2013;109:177-81.
4 Chiefs of Ontario. Prescription drug abuse strategy: 'Take a stand.' Final report. Toronto: Chiefs of Ontario; 2010. Available: www.chiefs-of-ontario.org/sites/default/files/files/Final%20Draft%20Prescription%20Drug%20Abuse%20Strategy.pdf (accessed 2016 March 17).
5 Health Canada. Honouring our strengths: a renewed framework to address substance use issues among First Nations people in Canada. Ottawa: Health Canada; 2011. Available: http://nnadaprenewal.ca/wp-content/uploads/2012/01/Honouring-Our-Strengths-2011_Eng1.pdf (accessed 2016 March 17).
6 National Advisory Council on Prescription Drug Misuse. First do no harm: responding to Canada's prescription drug crisis. Ottawa: Canadian Centre on Substance Abuse; 2013.
7 Canadian Medical Association. Policy Document PD15-06 - Harms associated with opioids and other psychoactive prescriptions drugs. Ottawa: The Author; 2015. Available: https://www.cma.ca/Assets/assets-library/document/en/policies/cma_policy_harms_associated_with_opioids_and_other_psychoactive_prescription_drugs_pd15-06-e.pdf (accessed 2016-March 17).
8 National Opioid Use Guideline Group. Canadian guideline for safe and effective use of opioids for chronic non-cancer pain. Hamilton, ON: McMaster University; 2010. Available: http://nationalpaincentre.mcmaster.ca/opioid/ (accessed 2016 March 17).
9 Dowell D, Haegerich TM, Chou R. CDC guideline for prescribing opioids for chronic pain-United States, 2016. MMWR Recomm Rep. 2016;65(RR-1):1-49. Available: http://www.cdc.gov/mmwr/volumes/65/rr/rr6501e1er.htm?s_cid=rr6501e1er_w (accessed 2016 March 17).
10 Walley AY, Xuan Z, Hackman HH, et al. Opioid overdose rates and implementation of overdose education and nasal naloxone distribution in Massachusetts: Interrupted time series analysis. BMJ. 2013;346:f174. Available: http://www.bmj.com/content/bmj/346/bmj.f174.full.pdf (accessed 2016 March 17).
11 Banjo, O, Tzemis, D, Al-Outub, D, et al. A quantitative and qualitative evaluation of the British Columbia Take Home Naloxone program. CMAJ Open, August 21, 2014;2(3) E153-E161. Available: http://cmajopen.ca/content/2/3/E153.full (accessed 2016 March 17).
12 Carter CI, Graham B. Opioid overdose prevention & response in Canada. Policy brief series. Vancouver: Canadian Drug Policy Coalition; 2013. Available: http://drugpolicy.ca/solutions/publications/opioid-overdose-prevention-and-response-in-canada/ (accessed 2016 March 17).
13 Canadian Medical Association. Policy Resolution GC15-18 - National strategy on the use of naloxone. Ottawa: The Author; 2015. Available: policybase.cma.ca/dbtw-wpd/CMAPolicy/PublicB.htm (accessed 2016 March 17).
14 United Nations Office on Drugs and Crime / World Health Organization Opioid overdose: preventing and reducing opioid overdose mortality. Discussion Paper UNODC/WHO 2013. Available: http://www.unodc.org/docs/treatment/overdose.pdf (accessed 2016 March 17).
15 American Medical Association. AMA adopts new policies at annual meeting. Press Release. New York, NY: Reuters; June 19, 2012. Available: http://www.reuters.com/article/idUS182652+19-Jun-2012+GNW20120619 (accessed 2016 March 17).
16 Drug Policy Alliance. American Public Health Association Policy Statement on Preventing Overdose Through Education and Naloxone Distribution. New York, NY: Drug Policy Alliance; October 30, 2012. Available: http://www.drugpolicy.org/resource/american-public-health-association-policy-statement-preventing-overdose-through-education-a (accessed 2016 March 17).
17 Canadian Pharmacists Association. CPhA Welcomes Health Canada Move to Change Prescription Status of Naloxone. News Release. January 14, 2016. Available: https://www.pharmacists.ca/news-events/news/cpha-welcomes-health-canada-move-to-change-prescription-status-of-naloxone/ (accessed 2016 March 17).
18 Health Canada. Consultation on the Prescription Drug List: Naloxone. File number: 16-100479-342. January 14 2016. Ottawa. Available: http://www.hc-sc.gc.ca/dhp-mps/consultation/drug-medic/pdl_ldo_consult_naloxone-eng.php (accessed 2016 March 17).
19 United Nations Office on Drugs and Crime / World Health Organization Opioid overdose: preventing and reducing opioid overdose mortality. Discussion Paper UNODC/WHO 2013. Available: http://www.unodc.org/docs/treatment/overdose.pdf (accessed 2016 March 17).
Submission to the Health Canada consultation on the potential risks, benefits and impacts of changes to the regulations to the Controlled Drugs and Substances Act that would require all products containing codeine to be sold by prescription only
The Canadian Medical Association (CMA) is pleased to provide this submission in response to Health Canada's notice as published in the Canada Gazette, Part I1 for interested stakeholders to provide comments on the potential risks, benefits, and impacts of changes to the regulations to the Controlled Drugs and Substances Act that would require all products containing codeine to be sold by prescription only.
Codeine is a widely used narcotic analgesic in Canada - low dose formulations are currently sold without a prescription, when in combination with at least two other medications. It is not available for self-selection, but kept behind the counter in pharmacies.
However, serious concerns have been raised about the safety of this practice in recent years.2,3,4 A literature review examining over the counter medicine abuse in several countries found that "there is a recognized problem internationally involving a range of medicines and potential harms," including codeine-based medicines.5
Doctors support patients in the management of acute and chronic pain, as well as addictions, and as such we have long been concerned about the harms associated with opioid use, including codeine. Codeine is considered to be "a poor analgesic in its own right," for which there are more suitable alternatives.6 In addition, genetic factors can substantially affect the metabolism of codeine into morphine, resulting in concentrations that vary from person to person. This can lead to potentially serious consequences, even at conventional doses, particularly in children.2
Codeine has the potential for dependence. Studies show an increase in non-therapeutic use of codeine, including over the counter formulations, leading to increases in morbidity and mortality as well as social costs. 7,8,9 An Australian study noted that "codeine-related deaths (with and without other drug toxicity) are increasing as the consumption of codeine-based products increases."10 Ontario data shows that over 500 people began methadone treatment for non-prescription codeine, between 2011 and 2014.3
In addition, over the counter codeine is often combined with acetaminophen or ASA, which also present concerns in terms of toxicity, particularly in higher doses.
A review of the process examining the problems related to codeine-based over the counter formulations in Australia, New Zealand, and the United Kingdom found that each of their respective committees had decided, based on the existing evidence, "to minimize harm by using regulatory levers to restrict availability."11 Many European countries have also implemented a prescription-only status for products containing codeine, as well as some U.S. States. Some Canadian hospitals have removed codeine from their formularies, and Manitoba ended the over the counter sales last year12.
Given this reality and, as part of the CMA's advocacy to reduce the harms related to opioid use, the CMA supports the requirement that all products containing codeine be sold by prescription only, as this is both a public health and a patient safety issue.
Moving codeine to prescription-only will enable limiting its use and closer monitoring of patients with the view of preventing harms.10 A challenge for policy makers and prescribers is to ensure patients still have access to treatments that are appropriate for their clinical conditions.13
At the same time, we recognize that there could be unintended consequences when moving low-dose codeine to prescription-only status, particularly for those who have come to depend on its availability over-the-counter. Some may choose to seek out illicit markets for these products or purchase other, more powerful, narcotics as a substitute. Authorities must develop educational tools to inform people about less-harmful pain-relief options. As well, a reasonable timeframe for implementation of this measure should be given to allow for patients to find appropriate alternatives.
The CMA continues to urge governments to increase access to services and treatment options for addiction and pain management, as well as harm reduction.14
1 Controlled Drugs and Substances Act: Notice to interested parties - Non-prescription availability of low-dose codeine products. Canada Gazette Part I. 2017 Sep 09, 151(36). Available: http://www.gazette.gc.ca/rp-pr/p1/2017/2017-09-09/html/notice-avis-eng.php#ne3 (accessed 2017 Nov 07).
2 MacDonald N, MacLeod SM. Has the time come to phase out codeine? Can Med Assoc J 2010;182(17):1825. Available: https://doi.org/10.1503/cmaj.101411 (accessed 2017 Nov 07).
3 Yang J, Zlomislic D. Star investigation: Canada's invisible codeine problem. The Toronto Star. Jan. 17, 2015. Available: https://www.thestar.com/news/canada/2015/01/17/star-investigation-canadas-invisible-codeine-problem.html (accessed: 2017 Nov 7).
4 MacKinnon, JIJ. Tighter regulations needed for over-the-counter codeine in Canada. Can Pharm J Rev Pharm Can, 2016;149(6):322-4. Available: http://www.cmaj.ca/content/182/17/1825 (accessed 2017 Nov 07).
5 Cooper RJ. Over-the-counter medicine abuse - a review of the literature. J Subst Use, 2013 Apr;18(2):82-107. Available: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3603170/pdf/JSU-18-82.pdf (accessed: 2017 Oct 23).
6 Vagg M. Four reasons why codeine should not be sold without a prescription. The Conversation. Apr. 30, 2015. Available: http://theconversation.com/four-reasons-why-codeine-should-not-be-sold-without-prescription-41025 (accessed: 2017 Oct 23).
7 Nielsen S, Cameron J, Pahoki S . Over the counter codeine dependence final report 2010. Victoria: Turning Point, 2010. Available: http://atdc.org.au/wp-content/uploads/2011/02/OTC_CODEINE_REPORT.pdf (accessed 2017 Nov 07).
8 Fischer B, Ialomiteanu A, Boak A, et al. Prevalence and key covariates of non-medical prescription opioid use among the general secondary student and adult populations in Ontario, Canada. Drug Alcohol Rev 2013;32(3):276-87.
9 Compton WM, Volkow ND. Major increases in opioid analgesic abuse in the United States: concerns and strategies. Drug Alcohol Depend 2006 Feb 01;81(2):103-7.
10Roxburgh A. et. al. Trends and characteristics of accidental and intentional codeine overdose deaths in Australia. Med J Aust 2015; 203(7): 299
11 Tobin CL, Dobbin M, McAvoy B. Regulatory responses to over-the-counter codeine analgesic misuse in Australia, New Zealand and the United Kingdom. N Z J Public Health 2013 Oct. 37(5): 483-488. Available: http://onlinelibrary.wiley.com/doi/10.1111/1753-6405.12099/abstract (accessed: 2017 Nov 7).
12 Zlomislic, D. & Yang, J. The Toronto Star. Jan 12, 2016. Available: https://www.thestar.com/life/health_wellness/2016/01/13/manitoba-sets-new-rule-limiting-codeine.html (accessed: 2017 Nov 7).
13 Canadian Medical Association. Opening Statement addressing the opioid crisis to the House of Commons Standing Committee on Health. Ottawa: The Association; 2016 Oct. Available: https://www.cma.ca/Assets/assets-library/document/en/advocacy/submissions/hesa-opioid-study-opening-remarks-oct-18-2016-e.pdf (accessed: 2017 Nov 7).
14 Canadian Medical Association. Harms Associated with Opioids and Other Psychoactive Prescription Drugs. CMA Policy, 2015. Ottawa: The Association; 2015. Available: https://www.cma.ca/Assets/assets-library/document/en/policies/cma_policy_harms_associated_with_opioids_and_other_psychoactive_prescription_drugs_pd15-06-e.pdf (accessed: 2017 Nov 7).