Responding to an earlier post by Professor David Currow and Professor Miriam Johnson, Professor Lukas Radbruch, President of the German Association for Palliative Medicine (Deutsche Gesellschaft für Palliativmedizin, DGP), gives another perspective from Germany.
Professor Lukas Radbruch.
David Currow and Miriam Johnson have explained in their recent post that even though many patients with chronic breathlessness will benefit from regular, low dose, sustained-release morphine, many physicians around the world are concerned about using morphine because it has not been licensed for chronic breathlessness. They describe that the Therapeutic Goods Administration (TGA) has approved the use of Kapanol™, a sustained release morphine capsule, for chronic breathlessness due to any cause. This is the first time that a medication for the symptomatic treatment of chronic breathlessness has been licensed. However, from our experience in Germany I am not so sure about the authors’ conclusion that this is a watershed from no indication to indication, and no standard to standard of care.
Using opioids, and specifically morphine, for the relief of breathlessness in cancer and non-cancer patients has been part of palliative care textbooks and palliative care guidelines for some years. The German evidence-based guideline on palliative care for patients with advanced cancer includes the following recommendation:
Patients with non-curable cancer and breathlessness should be treated wtih oral or parenteral opioids for the symptomatic relief of breathlessness.
There is another recommendation stating that the starting dose should be 15-30 mg oral morphine, but dosage increases might be necessary. This is in contrast to the Australian licence, which has a dose range up to 30 mg per day. This guideline was implemented in 2015, and was only recently updated in 2019.
This means that in Germany there is a standard, and an indication, for the use of opioids such as morphine for chronic breathlessness in cancer patients. I would use an evidence-based guideline in any (legal or scientific) guideline as proof of standard and proof of indication. There are quality standards in the production of high-level guidelines, for example the use of expert monitors, similar to quality standards for licensing procedures.
There is an ongoing discussion in Germany (as in other high-income countries) about off-label use of medications in palliative care. Off-label means that substances are used for specific indications, even though they have not been licensed for this indication. As Currow and Johnson have said, there is no opioid licensed for breathlessness (apart from Kapanol in Australia).
However, licensing often depends rather on how much money the company wants to spend on the licensing process. Licensing with the Food and Drug Administration (FDA) in the US or the European Medicines Agency (EMEA) in Europe is much more expensive and time-consuming than elsewhere. Many companies would not want to embark on this endeavour, especially as it would generate little additional income, as patients are already treated according to the guidelines recommending opioids for breathlessness. This is not only a problem for breathlessness, but also for many other indications and medicines. For example, a number of medicines such as gabapentin or paroxetine might be effective for the treatment of itching but none of those has been licensed for this indication.
As this is a frequent problem in palliative care, the German Association for Palliative Medicine has produced a brochure on the use of off-label medications. The use of morphine for breathlessness is used as an example in this brochure. This paper explains to palliative care specialists when and how medicines might be used off-label, and what the legal or financial implications are. For example, in most settings sickness funds will reimburse medication costs, even for off-label use, if there is adequate scientific evidence on the effectiveness, and no licensed alternative is available.
I would be really reluctant to use the Australian licence now to suggest that physicians in poorer countries use Kapanol for breathlessness instead of cheaper generic morphine. We can use the evidence, for example as provided in high-level evidence-based guidelines, to provide guidance and justify the off-label use of medicines!
What do other readers think?
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Links
- Read the earlier post by David Currow and Miriam Johnson, ‘Good news for chronic breathlessness from Down Under’ here.
- Read more posts about breathlessness on the EAPC blog.
- Contact Lukas Radbruch by email.
- German Association for Palliative Medicine website.
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