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from previous page false reassurance about safety, he warned.
“ Patches just have too good a reputation and it hasn’ t been sullied enough by fact yet.”
Expert testimony Australian Doctor contacted Professor Joyce last month. He said he could not talk because he was still providing evidence for the inquest.
We also approached pain specialist and anaesthetist Professor Stephen Schug from the University of WA, the other doctor who gave expert testimony to the inquest.
The director of pain medicine at Royal Perth Hospital, Professor Schug worked in one of the first centres testing transdermal fentanyl patches in the early 1980s in Germany.
“ Fentanyl patches were primarily developed as a way of giving medication ideally to patients who can’ t swallow and that was in principle cancer pain patients in terminal stages who had either gastric oesophageal cancer or who were unconscious,” Professor Schug explains.
It overcame the need to carefully titrate a subcutaneous infusion with a pump, and carried the added benefit that it prevented the constipation that came with oral opioids.
“ They actually became very popular for cancer pain treatment and were initially only licensed for that,” he says, but even from the outset, there were early efforts to promote the patches for acute pain relief.
“ There was this erroneous belief that because opioids are good for the treatment of cancer pain they’ re good for the treatment of non-cancer pain— which has resulted in the opioid epidemic,” he adds.
He blames this, partially, on Alza, the company that developed the patches initially.
“ I was one of the people on the advisory committee. They came to us and we said,‘ this is a crazy drug for post-operative pain, it takes 24 hours to reach peak and then if the patient is getting less pain, the drug is already in the system— it’ s like an infusion you can’ t switch off’,” Professor Schug explains.
But he says their advice was not heeded and the company published trial studies in a number of anaesthesia journals instead, and while they ultimately failed in getting US Food and Drug Administration( FDA) approval for it to be used in post-operative pain, the damage was already done.
“ Because so many surgeons had now read in journals this [ fentanyl ] was a very good drug for post-operative pain, they began using it. The US then had about 70 deaths in post-operative patients,” he says, before the FDA tightened restrictions on its indications.
“ Imagine going in for something like a hernia repair, you are 70 years old, you get a patch, you go home— you don’ t wake up the next morning,” he says.
Professor Schug believes most of the problems he sees with fentanyl stem from poor prescribing.
“ All doctors can prescribe them all over Australia, but while a microgram sounds small, it’ s very potent, which is misleading,” he explains.
If a prescriber gets the dose wrong, a patient using a patch will accumulate more and more fentanyl over 72 hours.“ It’ s an incredibly unforgiving drug.”
Before this is seen as GP bashing, he points out that in his own hospital, Royal Perth, only doctors from the pain service and palliative care service are allowed to prescribe new fentanyl patches.
“ We had potentially dangerous situations and decided the only safe way forward was to allow doctors who knew what they were doing with these drugs to start prescribing them— no other doctor,” he stresses.
Opioid epidemic Given the global concern surrounding opioid misuse, fentanyl patches occasionally hit the headlines, usually as a result of a celebrity death.
In April last year for instance, musical superstar Prince died from an accidental overdose of fentanyl. It is still not yet known whether Prince obtained the fentanyl by prescription or through an illicit channel.
The drug is a major factor in Australia’ s ever expanding list of opioid-related deaths, according to the Penington Institute, a drug abuse think-tank based in Melbourne. Fentanyl-related accidental deaths increased more than eightfold from 57 between 2001 and 2005, to 589 between 2011 and 2015.
And while the WA coroner was making public her call for restrictions on GPs, the RACGP was already working on revamping its guidelines on opioid prescribing, including the use of fentanyl patches.
Last week it unveiled its updated advice at the college’ s annual conference in Sydney. The report sets a new 12-point challenge to the speciality to reduce inappropriate opioid prescribing for both acute and chronic pain.
Dr Evan Ackermann, a GP in Warwick, Queensland and chair of the RACGP expert committee on
‘ WE’ VE GOT THIS CRAZY PBS SCHEME WHICH ALLOWS PEOPLE TO GET A ONE-MONTH SUPPLY OF ANY OPIATE THEY LIKE. IF THEY’ RE ON A PENSION THAT’ S SIX BUCKS.’
— Dr Simon Holliday, former chair of the RACGP’ s pain special interest group
The popstar Prince died after overdoing on fentanyl in April 2016.
FENTANYL – A SHORT HISTORY
• Fentanyl was first developed by Dr Paul Janssen in 1960 and entered medical use as a general anaesthetic under the trade name Sublimaze in the 1960s.
• When fentanyl hit the market, it was 10 times more potent than recently synthesised phenoperidine and found to be 100-200 times more potent than morphine in most animal models.
• When it was first created, it was considered the most potent opioid in the world. It had the fastest onset of action and highest therapeutic index( 277 vs 4.7, 71, and 39.1 for meperidine, morphine, and phenoperidine respectively) ever measured in an opioid.
• Janssen, the pharmaceutical company, initially had difficulty getting US Food and Drug administration approval for
quality care, says:“ One of the elements is about fentanyl. The guidelines currently state that the patches can be used for chronic severe pain. That will change, but I do have to be clear: for use in malignant pain in cancer, the patches are great. They are a godsend for doctors and GPs should use them when they believe they are appropriate.
“ But for the use of chronic pain without malignancy, we believe their use should be questioned and the new guidelines reflect fentanyl, encountering staunch opposition from Dr Robert Dripps, a professor of anaesthesiology at the University of Pennsylvania, who feared it was too potent could lead to many abuse problems.
• Fentanyl became a popular choice for anaesthetists in the 1970s and 1980s for cardiac and vascular surgery.
• Its success in the 1980s as an anaesthetic led to the development of the‘ super fentanyls’ for potential use as wild animal immobilisation drugs and as antiterrorist agents.
• Fentanyl patches, the first transdermal opioid, were approved by the FDA in the US for patients with cancer in 1990.
• In Australia, Fentanyl patches were listed on the PBS for cancer pain in 1999.
that. Part of the issue is the 25mcg patch. That is close to 60-80mg of morphine. It’ s a very high dose given very quickly and there is a deceptive feel about it.”
Taree GP Dr Simon Holliday is the former chair of the RACGP’ s pain special interest group. He echoes Dr Ackermann’ s point.
“ Fentanyl is a fabulous drug … and a wonderful anaesthetic agent, but on the other hand its particular issue is it’ s incredibly addictive. It can be boiled up to a tea in a jiffy and one patch can be cut into 10 sections and sold for $ 50 each,” he says, adding there’ d been a number of overdoses due to fentanyl in his area in the past few months.
“ But I don’ t think restricting GPs per se [ as some pain specialists are suggesting ] is the way forward. It’ s not just GPs that are the problem. We’ ve got this crazy PBS scheme which allows people to get a one-month supply of any opiate they like. If they’ re on a pension
• Transmucusoal fentanyl delivery systems such as the fentanyl lozenge also emerged in the 1980s when US researchers were looking into Janssen’ s carfentanil( an ultra-potent cousin of fentanyl) and whether, as an immobilising drug, it could be used in darts, aerosols and other delivery systems for wild elk, moose, and Rhesus monkeys. The researchers, drinking coffee one day during the Rhesus monkey trials, noticed how they loved to suck the sugar cubes. So they decided to inject the cubes with carfentanil in different doses. They witnessed how the monkeys on higher doses became deeply narcotised, to the extent that an awake endotracheal intubation was possible.
Source: Journal of Pain 2014; online.
that’ s six bucks,” he says.
“ A real-time prescription monitoring program will do very good things in terms of picking up which doctors are high prescribers and those doctors might well need some more assistance so they know how to be a bit more careful [ prescribing opiates ],” he says.
“ We need to have the PBS rationalise the way it handles opiates to be more evidence-based, supporting opiates for acute trauma, intensive care, and palliative care, and stop subsidising the majority of that which is for chronic noncancer pain.
“ I think any doctor that wants to prescribe an opiate should have to do some mandatory training in pain management and opiates.”
And perhaps capturing the life and death nature of what is at stake, Dr Holliday adds:“ It should be just like we have mandatory CPR training for doctors.” ●
Additional reporting Paul Smith
12 | Australian Doctor | 3 November 2017 www. australiandoctor. com. au