Below is an article that ran earlier this week in the Crikey bulletin raising concerns about the ongoing availability of two pain management medicines, and the processes that have enabled this.
Carol Bennett, CEO of the Consumers Health Forum of Australia, says the TGA has found the drugs, Di-Gesic and Doloxene, to be of questionable effectiveness in relieving pain while having significant safety issues. Yet they remain freely available – an example that she says raises concerns about corporate practices and bureaucratic processes.
Below her article is a response from Aspen Pharmacare Australia.
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Australia allows unsafe medicines to stay on the market
Carol Bennett writes:
There is something seriously wrong when a major pharmaceutical company can veto patient safety, and when they can seem to undermine the nation’s drug regulator to safeguard profits.
The Therapeutic Goods Administration (TGA) recently ordered two pain management medicines off the shelves following concerns regarding their safety and efficacy.
The drugs, Di-Gesic and Doloxene, were found by the TGA to be of questionable effectiveness in relieving pain and also have significant safety issues, with evidence that the drugs interfered with the electrical activity of the heart. This increases the risk of arrhythmia, when irregular beating of the heart can cause a wide range of serious consequences.
Using its regulatory powers, the TGA announced its intention to remove the products from the market, effectively banning sales in Australia. Two other drugs containing the same active ingredient, dextropropoxyphene, were also removed.
A number of other jurisdictions such as the US, UK, European countries and New Zealand have already removed these products from their markets in response to the same concerns.
Up until this point the system to protect patient safety seems to have worked; the TGA stepped in to remove a dangerous product from the market once sufficient evidence of danger to everyday consumers, outweighing any potential benefits, had been identified.
The story soured, however, when the product’s manufacturers, Aspen Pharmaceuticals, decided to challenge the ruling in the Administrative Appeals Tribunal (AAT) on an administrative technicality.
The AAT then issued a stay order, effectively overriding the TGA’s concerns about consumer safety, and allowed the products to continue to be sold.
Aspen were ordered to circulate strong warnings to doctors and pharmacists and place statements on the product itself.
The outcome is that the medication is still available on the market, and consumers are still at risk of very serious side effects.
There are two elements to this story that should concern all of us: the company involved appears to have put its corporate interests ahead of concerns about health and safety; and the TGA, Australia’s medicines regulator, has been sidelined by the decision of a quasi-judicial administrative panel.
In this day and age of triple bottom line reporting and corporate responsibility, I find it amazing that Aspen Pharmaceuticals thought it in any way ethical or appropriate to immediately appeal on technical grounds and ignore the substantial medical evidence.
Aspen is entitled to recourse to appropriate legal remedies, and they should be afforded review and appeal.
However, if Aspen are confident that these products were safe and effective they could have worked with the TGA to ensure regulatory compliance and demonstrate the appropriate management of potential risk to patient safety so the ban could be reversed.
Should Aspen should be putting the lives of their patients ahead of their own corporate interests?
If they were serious about being a company dedicated to health and wellbeing, they would remove these products from the market until safety concerns could be properly addressed.
The second, and perhaps equally worrying issue, is the effective erosion of the TGA’s ability to use its expert knowledge to safeguard patient safety by the AAT.
The TGA does not often ban products.
The TGA thought it appropriate to fully remove Di-Gesic, Doloxene and other medications from the market and this should be enough to ensure these products are not available to the public unless they are proven to be safe and effective.
It does not bode well for future regulation that a tribunal can easily overturn the very thorough and painstaking review of medications undertaken by the TGA on a very narrow technical ground in the face of substantial evidence.
Imagine what would happen if the car industry could stall the recall of a car that had been manufactured with faulty brakes on the basis of some technical administrative issue that had nothing to do with the actual safety of the car?
Imagine that the same car had been recalled in other countries for the same issues? Would anyone support such an absurd outcome that puts the lives of Australian drivers and other road users at risk for no good reason?
Aspen, a South African listed company, has a $5.9 billion market capitalisation, and boasts sales of over $700 million in Australia and New Zealand. This level of resourcing enables it to pursue legal action and other strategies that can stall any efforts to remove products over which genuine concerns have been raised.
I think all Australians should be very concerned by this episode, and the apparent ease with which a major pharmaceuticals company can stall the actions of the nation’s drug regulator.
Aspen has a duty of care to their patients who trust the product they are bringing to market is safe, effective and has been thoroughly tested; a duty they now appear to be placing second to their corporate interests.
At the end of the day, consumers trust the products they are being sold are safe and effective, have been appropriately tested and will not potentially harm their health.
It’s disappointing that Aspen seems to have taken the low road to the dollar. Such action could permanently undermine the trust relationship they have with their consumers as well as those involved in the broader medicines industry.
The lesson is that when it comes to the behaviour of some big pharmaceutical companies, profits certainly take priority; safety concerns may or may not.
• Carol Bennett, CEO, Consumers Health Forum of Australia
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Aspen’s response
Greg Lan, CEO of Aspen Australia, writes:
Aspen Pharmacare strongly rejects the false and misleading claims made by Carol Bennett, the CEO of the Consumers Health Forum of Australia, in an article published on Crikey.
The opinion piece focussed on the pharmaceutical company’s successful appeal to the Administrative Appeals Tribunal (AAT) regarding the decision by the Therapeutic Goods Administration (TGA) to cancel the registration of two painkillers containing dextropropoxyphene (DPP) – Doloxene and DiGesic.
Contrary to Ms Bennett’s assertion, the decision was not based on “an administrative technicality” but on the evidence presented to the AAT.
Only someone uninformed about the process and the evidence could have drawn the conclusions Ms Bennett did.
The decision
After hearing the parties and their respective experts, including a cardiologist, pain management expert, toxicologist and pharmacologist for five days in early June, the AAT decided to remit the decision to cancel the registrations of the two products to the TGA for reconsideration, particularly with a view to ensuring DiGesic and Doloxene remain available to patients who are not adequately treated with alternative analgesics.
Aspen agrees that both products should remain available for these patients.
Efficacy
Importantly, the AAT found that Doloxene and DiGesic are each effective in treating mild to moderate pain. Similarly, while no analgesic is effective in all patients, the data presented did not justify the conclusion that either DPP or DPP in combination with paracetamol lacked efficacy.
Safety
Significantly, the AAT recognised that the NSW Coroner records more deaths resulting from codeine, tramadol and paracetamol (which can be purchased without prescription, over the counter in a supermarket) than deaths resulting from DPP.
Aspen agrees with the AAT’s finding that “it is not appropriate to refuse registration approval for a preparation simply on the basis that it may be used deliberately for the purposes of self-harm”.
The AAT also accepted the evidence of Professor Horowitz, an expert cardiologist, that in the ordinary circumstances of prescribing, the potential for sudden death is “about zero”, as well as Cochrane Reviews (the highest quality reviews of clinical studies) which support a finding that the safety of DPP at therapeutic doses is no different from other weak opioids, and in some cases (such as when compared with tramadol) more tolerable.
The interests of patients
As noted already, the AAT was concerned to ensure that DPP remains available for patients for whom there is no suitable alternative to analgesics containing DPP.
Put another way, the AAT found that if DiGesic and Doloxene are not available, there will be a group of patients for whom there is unlikely to be an adequate analgesic alternative for the treatment of mild to moderate pain.
These are patients who suffer from pain for which ‘weak’ analgesics such as paracetamol and aspirin are inadequate, but which does not require a ‘strong’ analgesic such as morphine or oxycodone which pose a significant risk of dependence, and have side effects such as nausea, dizziness and “fogginess” which interfere with the tasks of daily life.
Codeine and tramadol are the only other ‘moderate’ analgesics which are available to treat these patients and while some respond well to these drugs, others obtain no analgesic relief at all because of a genetic mutation which prevents metabolism of these drugs via the CYP2D6 metabolic pathway.
Other patients, due to another genetic mutation which affects the CYP2D6 metabolic pathway, are super-fast metabolisers of codeine and tramadol such that administration of these drugs can result in toxicity.
Further, many patients experience intolerable constipation, nausea and vomiting when they take codeine, and dizziness and nausea when they take tramadol.
United Kingdom
It is also important to recognise that the UK regulator understands that there is a small group of patients for whom alternatives are not acceptable or suitable, and consequently, has ensured that DPP remains available in the UK for those patients who need it.
Aspen’s position
Aspen understands that, like many other prescription and over-the-counter drugs, DPP has the potential to cause harm if it is not used appropriately. Aspen also recognises that it may not be appropriate for DPP to be prescribed to patients where another moderate analgesic, such as codeine or tramadol, is sufficient.
However, we support DPP being available to patients who need it, and who will be left without satisfactory pain relief if DPP is removed from the market.
Aspen has received feedback from many doctors, pharmacists and patients who support the steps we have taken to ensure DPP remains available, and who recognise the difficulty that some patients will suffer if it is no longer available.
At Aspen, patient safety and quality care are our top priority and we will continue to operate with the utmost integrity in meeting the needs of the Australian community.
