For the first time in the world, an Australian company has licensed a medication for the symptomatic reduction of chronic breathlessness. Professor David Currow (Australia) and Professor Miriam Johnson (United Kingdom), explain.
Professor Miriam Johnson and Professor David Currow.
Breathing just happens. We don’t think about it, we just breathe. Sometimes we breathe harder and faster in response to the demand of physical exertion or emotion, but we don’t have to try – it just happens, and it can feel good. Our bodies produce their own morphine-like chemicals, endorphins, when we respond in this way – better known as the cause of the ‘runner’s high’.
However, millions of people around the world think about their breathing most, if not all, of the time. They live with medical conditions that affect breathing, such as chronic obstructive pulmonary disease (COPD), heart failure, or lung cancer. Everyday tasks like getting up, washed, and dressed, climbing stairs, preparing food or making a cup of tea – let alone getting to the shops – can cause distressing and disabling breathlessness. Eventually, life takes place within one room in the home apart from intermittent trips to hospital for terrifying times when their breathlessness gets even worse.
Fortunately, we are learning more about ways to help people manage such chronic breathlessness in addition to treating the person’s underlying medical conditions. 1 The mainstay of treatment is training to breathe efficiently, better ways to manage anxiety and panic, ways to keep physically and socially active, and by using a hand-held battery operated fan for cool facial airflow; mostly delivered by clinicians such as physiotherapists and occupational therapists. 2,3
Unfortunately, as a person’s condition worsens, so chronic breathlessness becomes harder to control with non-drug measures alone. About two in three people 4,5 will also gain some relief with regular, low dose, sustained-release morphine (about the same dose as two tablets of paracetamol-codeine combination four times a day) to supplement our own body’s endorphin response to exertion. Around the world, although some doctors are happy to prescribe it, others are concerned about using morphine because it has not been licensed for chronic breathlessness. In addition, there have been ongoing discussions about starting doses and titration.
However, that is changing. The Therapeutic Goods Administration (TGA), which licenses and monitors the use of medications in Australia has, for the first time in the world, licensed a medication for the symptomatic treatment of chronic breathlessness. This is a major step forward for millions of people around the world who are largely invisible to health practitioners, and for whom the response has been until now “Of course you’re breathless. You have advanced COPD.” This recognition opens a new conversation – “I can see you’re breathless doing basic things like getting dressed. How I can I help you to do this with less disabling breathlessness?”
Having independently and extensively examined the evidence on the effectiveness and safety of regular, low dose, sustained release morphine for chronic breathlessness, including having access to all analyses from the recently published MOP study 6 the TGA has approved the use of this medication. Kapanol™, the sustained release morphine capsule, is now licensed for use in chronic breathlessness due to any cause, starting at 10mg once daily, up to a maximum of 30mg once daily. From the beginning of September 2019, following a recommendation from Australia’s independent medication pricing authority the Pharmaceutical Benefits Advisory Committee (PBAC), the medication is also subsidised for the symptomatic reduction of chronic breathlessness.
So how does a licensing change on the other side of the world affect clinical practice elsewhere? Many countries can’t access Kapanol™. The answer is that this represents a watershed, from no regulatory-approved indication (independent of the clinicians who play a key part in clinical guidelines) to regulatory-approved indication, no licence to licence, and from no standard of care (developed using this level of scrutiny) to a world-first regulatory-approved standard of care. For too long, palliative care has relied on clinical guidelines driven by expert opinion, and of variable methodological quality. Even the most rigorous do not match the extent of data review, level of definition of net effect (benefits and harms), or independence from the clinicians invested in their proposed use necessary for regulatory approval. Where one country provides a licence, others are likely to follow to ensure people get access to medications that help, whilst keeping them safe.
The TGA review also identified gaps in the evidence – for example, the need for longer-term data, data from different disease groups (we have few data in relation to people with cancer), data relating to different opioids. This new baseline should stimulate a commitment to conduct the further studies that quality, evidence-based clinical practice relies on using methods that stand up to regulatory review. Such work requires us to work closely with colleagues in: the basic sciences; clinical pharmacology; in the case of opioids addiction services; family medicine; general medicine; and regulators whose sworn duty is to optimise the care that is offered to patients. Whenever we refuse to make this shift, we are potentially continuing to compromise the outcomes for the frailest of any patient population – those people with life-limiting illnesses. This is the level of rigour that the community rightly expects.
In the meantime, clinicians now have a standard dosing schedule to follow – even where Kapanol is unavailable, the principles of regular dosing to provide steady state can be applied – that has passed the scrutiny of independent monitors – also providing confidence and guidance. Clinicians therefore now have clearer guidelines to follow in the knowledge that they are prescribing in a responsible manner, including for the patients who may not be referred to palliative care services. This should result in many more people having safe access to a medication, which may help improve their quality of life and reduce their suffering.
- Johnson MJ, Yorke J, Hansen-Flaschen J, Lansing R, Ekström M, Similowski T,Currow DC. Towards an expert consensus to delineate a clinical syndrome of chronic breathlessness. Eur Resp Journal 2017; 0: 1602277 [https://doi.org/10.1183/13993003.02277-2016].
- Swan, F., Newey, A., Bland, M., Allgar, V., Booth, S., Bausewein, C., … Johnson, M. (2019). Airflow relieves chronic breathlessness in people with advanced disease: An exploratory systematic review and meta-analyses. Palliative Medicine, 33 (6), 618–633. [https://doi.org/10.1177/0269216319835393].
- Cambridge University Hospitals NHS Foundation Trust Breathlessness Intervention Service (BIS).
- Ekström E, MD, Bajwah S, Bland JM, Currow DC, Hussain J, Johnson MJ, One Evidence Base; Three Stories: Do Opioids Relieve Chronic Breathlessness? Thorax. 2018 Jan; 73 (1):88-90. [doi: 10.1136/thoraxjnl-2016-209868].
- Currow DC, McDonald C, Oaten S, Kenny B, Allcroft P, Frith P, Briffa M, Johnson MJ, Abernethy A. Once daily opioids for chronic dyspnoea: a dose increment and pharmacovigilance study. J Pain Symptom Manage 2011; 42 (3): 388 – 399: [doi:10.1016/j.jpainsymman.2010.11.021].
- Currow D, Louw S, McCloud P, et al Regular, sustained-release morphine for chronic breathlessness: a multicentre, double-blind, randomised, placebo-controlled trial. Thorax. Published Online First: 26 September 2019. [doi: 10.1136/thoraxjnl-2019-213681].
More about the authors…
David C Currow is Professor of Palliative Medicine, Faculty of Health, University of Technology Sydney, Ultimo New South Wales, Australia, and Associate Director of the Wolfson Palliative Care Research Centre, Hull York Medical School, University of Hull, Hull, UK. David has been a paid consultant to, and received intellectual property payments from Mayne Pharma International Pty Ltd, the manufacturers of KapanolTM.
Miriam J Johnson is Professor of Palliative Medicine and Director of the Wolfson Palliative Care Research Centre, Hull York Medical School, University of Hull, Hull, UK.
Follow Miriam on Twitter @MJJohnson_HYMS
Read more posts on breathlessness, including those from Miriam Johnson and David Currow, on the EAPC blog.