Following reports that one of the most widely used painkillers, the anti-inflammatory diclofenac (also known as Difene and Diclac), is linked to an increased risk of heart attack and stroke, the State’s medicines regulator this week advised people with heart problems to avoid using it.
The claim, made in a study published in the British Medical Journal, came as a shock to patients, but many doctors were already aware of the drug's side effects.
Terry Hyland Jnr from Lacken in Co Cavan has used Difene on several occasions in the past for numerous sport-related injuries. He was never told by doctors about the risks of heart attack and stroke but was told the drug could cause stomach problems, he says.
“It’s seen as a minor type of medication people take without consideration of risks. People wouldn’t think twice about taking it,” he adds.
“Certainly when I was playing football there would be lads passing it around the dressing room in the same way they would pass around an ice pack.
“There’s definitely a low-risk factor perception of the drug in people’s mind,” says the son of the Leitrim senior football team manager.
Diclofenac is used to treat a variety of ailments and conditions such as arthritis, osteoarthritis, back pain, headaches and neck pain, and has been around since the 1970s.
In 2013, a study of non-steroidal anti-inflammatory drugs (NSAIDs) in 15 countries found diclofenac was the most popular drug despite being associated with more cardiovascular complications than other such medications. The authors noted information on its higher cardiovascular risk had been available since 2006 but, despite this, the drug remained widely listed on national essential medicines lists.
In contrast, naproxen, generally considered the safest NSAID (though not without side effects) was among the least popular and included in only a minority of national essential medicine lists.
Most prescribed
Diclofenac is the most prescribed NSAID in Ireland, according to the 2016 HSE Primary Care Reimbursement Service (PCRS) Annual Report, which gives a comprehensive overview of prescribing trends in Ireland among public patients.
The report reveals there are 760,000 prescriptions for diclofenac for public patients each year. There is no data available on prescribing trends among private patients but GPs and nurses believe it is frequently prescribed privately.
It is time to acknowledge the potential health risk of diclofenac and to reduce its use
The BMJ study concluded that, given the heart and stomach risks, "there is little justification to initiate diclofenac treatment before other traditional NSAIDs".
“It is time to acknowledge the potential health risk of diclofenac and to reduce its use . . . and when prescribed, should be accompanied by an appropriate front-package warning about its potential risks.”
Diclofenac was previously available without prescription in the UK, but since 2015 is a prescription-only medication following patient safety concerns.
A 2013 European Medicines Agency review noted “the cardiovascular risk with any NSAID depends on a person’s underlying risk factors, such as high blood pressure and cholesterol levels and also any underlying heart or circulatory conditions”.
“About eight people in 1,000 at moderate risk of heart disease are likely to have a heart attack over one year. The overall number of heart attacks in people at moderate risk would be expected to increase by around three cases per year for every 1,000 people treated with diclofenac [to 11 per 1,000 people per year].”
Despite the advice, the agency concluded the benefits of the drug still outweigh the risks – a view held by many Irish healthcare professionals today.
In a statement, the European Medicines Agency said the safety of all medicines on the market was monitored continually.
A spokeswoman for the Health Products Regulatory Authority (HPRA), which monitors the safety of medicines in Ireland, said “this latest study will be considered as part of the ongoing regulatory review of safety-monitoring activities, in conjunction with our EU regulatory colleagues, and any changes needed will be implemented and communicated, as necessary”.
‘A lot of people are on it’
Given the breadth of research on the topic and the many safety warnings, it is reasonable to question why diclofenac is still the most prescribed NSAID in Ireland.
According to healthcare professionals, this is partly because patients are familiar with the brand Difene and often request the drug during consultations as they have found it to be highly effective in the past.
Dr Dominic Hegarty, a consultant in pain management and neuromodulation at the orthopaedic and spine centre in the Mater Private Hospital, Cork, said many patients were on diclofenac by the time they visit a pain specialist.
I think it gets prescribed a lot more often than we are willing to accept. A lot of people are on it
“That may be because they haven’t responded to the lower dosages of a lower agent and when that fails they get referred to a pain consultant. We tend to see a cohort of patients who have tried a lot of medications by the time they come to us,” he said.
“I see people taking a lot of Difene. I think it gets prescribed a lot more often than we are willing to accept. A lot of people are on it.”
He expressed little surprise at national figures showing diclofenac is the most frequently prescribed NSAID among public patients in Ireland.
But he cautioned patients against making rash decisions following the study.
“NSAIDs are still useful tools . . . what we do not want to see is people not writing up these agents and people on them for a period of time suddenly stopping them because of this report. All non-steroidals get put under the one umbrella that they’re all bad for you and, if people stop, we’ll lose a very valuable tool,” he said.
“For certain groups of people these are very useful drugs, not necessarily Difene, I’m talking about non-steroidals. They relieve people of pain and allow them to get by on a day-to-day basis and are well tolerated to a point.
An alternative NSAID, naproxen, is a useful tool, but “realistically it is certainly down the ladder in terms of potency compared with other agents that might be available . . . there’s no harm trying it but more often than not you will see people stepping up to the stronger anti-inflammatories that Difene offers them in that respect”.
Dr Hegarty said diclofenac was very useful in the early phases of sudden injuries such as fractures and sprained ankles.
It is written up “an awful lot” in hospitals, he observed. “I don’t like it being written up this much but it is and everybody probably goes home on a couple of these tablets [diclofenac] from A&E and from clinics because it works. But it’s aimed at short-term use and a line should be drawn under it fairly quickly so that it’s not taken for any longer than is absolutely necessary.”
The risk factors are still there, even for short-term use, he said, but perhaps they are not as high.
The real problems start for people when they still have pain after an injury and go back to their GP and stay on their prescription, which continues for several weeks.
“This is the cohort who get upset by the medication. They get stomach upset, heartburn, reflux, feel miserable and their bowel habits changes,” he said.
Risk
Notwithstanding high diclofenac prescription rates in Ireland, the drug was not the first NSAID usually prescribed by GPs, Waterford-based GP Dr Austin Byrne said.
All NSAIDs carried risk of adverse gastric, kidney and cardiac side effects, he said. But while alternative NSAIDs to diclofenac were relatively safer, “the absolute risk of harm is not that different”.
Absolute risk is defined as a person’s risk of developing a disease over a period of time while relative risk is used to compare risk in two different groups of people.
“Relative risk of an event is significantly higher on the drug [diclofenac]. Absolute risk remains very, very low. That’s the crux of the issue,” he said.
In his experience, patients discharged from hospital are too frequently prescribed diclofenac, particularly for fractures, and for women who have recently given birth.
He called for a system to help track prescribing in Ireland, a view echoed by many Irish doctors who have called for more support in devising structures to understand prescribing trends.
Multiple doctors start drugs and there needs to be someone checking bases
“We need a mechanism for GPs to perform periodic therapeutic reviews. Multiple doctors start drugs and there needs to be someone checking bases,” Dr Byrne said.
The fact that there are few substitutes to medicine for patients in Ireland was a huge concern, he said. “There are little alternatives to medication in Ireland. For patients with pain, simple effective interventions such as physio are a year wait. Pain clinics are inaccessible and there is no service in many regions,” he said.
‘Not dangerous if correctly used’
Ruth Morrow, an advanced nurse practitioner, explained that she dramatically reduced prescribing diclofenac when concerns first emerged over a decade ago. She is happy to prescribe the drug for short-term use but always avoids writing long-term prescriptions.
“Years ago there would have been patients on it long-term every day but we took them off it when the research came out and prescribe only for short-term usage now,” she said.
GP lecturer and researcher Dr Mark Murphy welcomed the BMJ study but said there was "not a lot new" in it. While the research should be taken seriously, he said the study showed serious complications were rare.
He recommended the lowest possible dose and the safest possible drug be used for the shortest period of time when prescribing.
Kerry-based GP Dr Eamonn Shanahan believes diclofenac is “not dangerous if correctly used”.
Some doctors believe one of the problems associated with widespread usage of a drug is that it can possibly lead to a greater risk of it is being abused.
Difficulties arise when patients self-prescribe. It is not uncommon to have some unused Difene lying in the cupboard from a previous prescription or to be offered some by a friend or relative to treat injuries and pain.
Dr Hegarty has come across many pain patients who self-prescribe in this way.
He maintained that obtaining the drug “inhouse” at home or from a family member was more common than anecdotal reports of people bulk buying the drug over the counter in Spain.
“You hear these stories of people buying the drug abroad, but certainly not as much as people would like to admit,” he said.
“It’s amazing. People go buy this stuff over in wherever-land and they really don’t know what they’re buying. They’ve bought a derivative of this and then suddenly they’ll be using some other ibuprofen-based product on top of the Difene and that’s really the risky bit.”
It [the report] should make the medical profession sit up and re-examine the rationale behind using this medication
He said the BMJ study "tells us nothing new" but serves as a reminder to healthcare professionals to ensure people are advised of potential side effects.
“It should make the medical profession sit up and re-examine the rationale behind using this medication and ask if the risk-to-benefit ratio is in the patient’s favour to use it.
“If there’s an element of inflammation, it’s a good choice but if there is no element of inflammation, then it’s a bad drug choice and one shouldn’t prescribe it.
“If you sprain your ankle, the swelling goes down within three to four days usually and, therefore, the inflammation concept is gone. So why would you continue to take something that is well past its time to be used? That is where the risks come in. Caution, timing and duration need to be looked at and focused on.”
