Should we be routinely co‐prescribing naloxone for patients on long term opioids?

Community naloxone supply to prevent fatal overdose needs to consider patients using pharmaceutical opioids

Pharmaceutical Benefits Scheme (PBS) opioid prescriptions in Australia have increased from 2.4 million in 1992 to 7 million in 2007 to 15 million prescriptions in 2016.1 The corresponding rate of opioid mortality over this time almost doubled from 3.8 deaths per 100 000 Australians in 2007 to 6.7 in 2017,2 with fatal opioid overdoses increasing from 482 in 2002 per 100 000 Australians to 900 in 2018.3 Most of these deaths involved prescription opioids, and contrary to what many assume, only one‐third of prescription opioid‐related deaths involved intravenous drug use.4 Among deaths associated with common prescription opioids (including fentanyl, morphine, oxycodone, tramadol and codeine), 49% involved people with chronic pain.4

Naloxone, a rapidly acting semi‐synthetic opioid antagonist, has an important role in reducing opioid overdoses by acting as an emergency reversal agent.5 It is currently available in Australia for intramuscular injection or nasal spray. The intranasal formulation was listed on the PBS in November 2019 as an unrestricted General Schedule medication. New South Wales, Western Australia and South Australia are trialling a program of take‐home naloxone available free to people using prescription or illicit opioids and at risk of opioid‐related death or those who may witness an overdose.5 Various aspects of patient history including current opioid medications (especially if the opioids are higher doses or slow release preparations) and comorbidities (such as complex diseases, mental illnesses or respiratory conditions) can help identify people who should be recommended to carry naloxone.5 Take‐home naloxone provided to laypeople to administer in the event of overdose was found to successfully reverse more than 96% of community overdoses in a systematic review.6 The evidence of naloxone’s therapeutic effect and life‐saving role has resulted in the drug being carried in most emergency medical kits and included on the World Health Organization Model Lists of Essential Medicines (https://www.who.int/groups/expert-committee-on-selection-and-use-of-essential-medicines/essential-medicines-lists).

Community members, general practitioners and pharmacists frequently perceive naloxone as a medication for people who use illicit opioids, namely heroin.7 However, opioid‐related mortality in people taking pharmaceutical opioids for chronic pain is common. There is a clear evidence–practice gap demonstrating the need for increased discussion about opioid‐related risks and naloxone in this population. In the context of rising pharmaceutical opioid harm, the United States Centers for Disease Control and Prevention provided recommendations for co‐prescribing naloxone for at‐risk patients with chronic pain; such patients include those taking an oral daily morphine equivalent dose of 50 mg or more, taking concurrent benzodiazepines with opioids, having a history of substance use disorder, or having a history of overdose.8 Using these indications, an Australian study reported that 78% of patients on Schedule 8 opioids for chronic non‐cancer pain qualified for take‐home naloxone.8,9 Yet current national data show that less than 3% of all naloxone supplied is on individual PBS prescriptions, with most naloxone prescriptions accounted for by harm reduction programs.10 An additional negligible amount of naloxone is sold over the counter by pharmacists.10 Between 2014 and 2018, an estimated 10 642 units of naloxone were supplied in Australia. Even if a large proportion of this were dispensed to people taking pharmaceutical opioids for chronic pain, it would be vastly insufficient given the 300 000 Australians receiving long term opioids each year.10,11 The majority of Australian patients on pharmaceutical opioids who are at risk of overdose do not appear to be prescribed this emergency medication.

Health care provider attitudes towards pharmaceutical opioid‐related risk may be contributing to low naloxone prescribing rates. In qualitative work, Australian GPs described hesitancy in prescribing opioids to younger and middle‐aged patients with chronic pain due to perceived risks of opioid‐related harm.12 In contrast, GPs were more comfortable prescribing opioids for older patients, as they believed there was a lower risk of serious opioid‐related harm in this population.12 These findings highlight doctors’ subjective judgements of overdose risk, which may be a barrier to recognising patients who would benefit from take‐home naloxone. Similar qualitative work highlighted that the biggest barriers to naloxone prescribing were low levels of awareness about naloxone, and unwillingness by doctors to prescribe it.7 This may be driven by incorrect beliefs that patients on pharmaceutical opioids are at low risk of overdose, lack of knowledge, and incorrect patient reporting of actual opioid use.7

GPs and pharmacists are ideally placed to provide and advocate for routine take‐home naloxone. GPs prescribe just over half of all opioids in Australia13 and are the main health care professional seen regularly by people taking opioids for chronic pain. Conversations about naloxone initiated by health care providers present an opportunity to highlight proactive steps to reduce opioid‐related risk, and also raise awareness of overdose management. Unfortunately, community knowledge about opioid‐related risk is low, and most people prescribed opioids for pain are unable to identify common signs of potentially fatal opioid toxicity.14 Improved naloxone prescribing alone is therefore unlikely to be effective without education and increased awareness of opioid overdose signs by patients, family members, friends and carers — who are the expected administrators of naloxone in the event of overdose.

One commonly cited barrier to prescribing take‐home naloxone is fear that patients may be offended by the offer or recommendation.7,14 However, Australian research shows that when informed about naloxone, most people prescribed opioids for pain would want or in fact expect their doctor to prescribe it to them.14 Sensitivity around language is key to openly communicating with patients about this issue. Terms like “overdose” still carry considerable stigma and are poorly understood by laypeople. A more patient‐centred approach (and to avoid having important health messages dismissed as irrelevant by patients), might involve changing our language to use terms like “severe opioid‐related side effects” or “life‐threatening opioid toxicity” instead of “drug overdose” to explain the same concept.

Discussing naloxone may also help patients recognise the level of harm associated with non‐indicated opioids. The therapeutic benefit of opioids for chronic pain is limited and guidelines strongly caution their use.13 Presenting naloxone as a necessary medication for people on long term opioids may help patients better understand the implications of taking these strong analgesics. This may intuitively encourage patients to request opioid deprescribing or dose reductions. Conversely, increased prescribing of naloxone may risk providers (and patients) justifying high dose opioid prescriptions by relying on naloxone as a safety net. These fears are common with opioid harm minimisation efforts but are not supported by evidence6 and should not detract from the expected number of lives that could be saved by naloxone.

A novel approach may be to consider routine co‐prescription of naloxone for patients on strong long term opioids. Laxatives and antiemetics are commonly co‐prescribed with opioids by providers cognisant of common opioid side effects; however, this concept does not seem to extend to naloxone. Take‐home naloxone for people on opioids is analogous to intramuscular glucagon for patients with diabetes on insulin, or auto‐injectable adrenaline for anaphylaxis. Most people are unlikely to need these emergency medications, but in the case of profoundly dangerous adverse events, naloxone, like glucagon or adrenaline, has a life‐saving role.

Changing the narrative around take‐home naloxone from “overdose treatment” to “routinely prescribed emergency medication” may help provider attitudes and encourage the normalisation of naloxone prescribing. Our conservative estimate suggests that about 200 000 naloxone scripts would be indicated annually using this approach, at a cost of $40–50 each on the PBS.8 This is comparable with the PBS cost of an adrenaline auto‐injector or glucagon, which are both listed at $40.15 The estimated volumes of naloxone required would also be similar to combined PBS prescription volumes of glucagon (about 44 000 prescriptions) and adrenaline auto‐injectors (about 110 000 adult prescriptions and 28 000 paediatric prescriptions) according to Medicare statistics of PBS prescriptions from July 2019 to June 2020, excluding doctor’s bag prescriptions.15 We present these comparisons between naloxone and other widely accepted emergency medications to show the severity of current naloxone under‐prescribing. From a health economics perspective, increased naloxone prescribing at the rates we suggest would cost the Australian a similar amount to glucagon and adrenaline combined through PBS reimbursement. Further, naloxone would still cost only a fraction of current PBS‐subsidised opioid prescriptions (oxycodone alone costing over $61 million in 2018–201915) and overdose‐related hospitalisation costs. Naloxone may assist with reducing opioid prescription rates and cost, and most importantly would save lives.

GPs and pharmacists should consider discussing and co‐prescribing take‐home naloxone with opioids for patients with chronic pain. Australia’s increasing prescription opioid overdoses demands this conversation. However, normalising the role of naloxone as a routinely co‐prescribed emergency medication will require major changes in community and health care provider attitudes, improved awareness of the role of naloxone, and reduction of overdose‐associated stigma. Ongoing collaborative efforts are needed to embrace higher prescribing and dispensing of naloxone.