'Game changer' a bitter pill

TONY WALL

Pharmac touts blood-thinning drug Pradaxa as a 'game changer' for heart patients. But many of our elderly have had horrific experiences and there is concern at the way it was rolled out. By Tony Wall. 

Whangarei man Rex Smith took the new blood-thinning drug Pradaxa on a Thursday – by Monday he was in North Shore Hospital's intensive care unit with massive internal bleeding. Three weeks later he was dead.

His family is angry that Rex, 82 and living alone, was prescribed Pradaxa when little is known about managing its side effects. His son, Russell, says Rex was on warfarin for many years for his irregular heart. He had had a bypass and a valve replacement. Rex recently went to his GP in Whangarei and was diagnosed with pneumonia.

"The doctor said, 'antibiotics and warfarin are not a good mix, I'll give you the new wonder drug, which I've never given anyone before. It's just come out this week'," Russell says.

Russell collected his father from Whangarei and took him to Auckland, where he was admitted to hospital and given multiple blood transfusions. "They said he was the first one they'd ever seen on the new drug, that it was completely irreversible and that he had three to four days to live. They said to me if it was warfarin, we could stop it [bleeding] straight away, but they didn't have anything to stop it with."

Rex improved for a while but died three weeks later.

Russell says he has not spoken to the GP but understands he is "devastated".

"I'm pissed off, I don't think it's had enough trials," said Russell. "My GP said, 'it's too soon for me to use it, I'm a bit wary about new stuff like this – there's been no track record'."

After an article on Pradaxa in the Sunday Star-Times last weekend, we were inundated with emails from readers who had seen adverse reactions to the drug, from gastro-intestinal problems to serious bleeds. Four families said a loved one had died shortly after being switched from warfarin to Pradaxa, although what role the drug played in the deaths remains unclear.

Proponents of Pradaxa say it is an exciting new drug with a big future; that all drugs have side effects; and when any new medicine is introduced there are problems.

Critics are alarmed at the way it has been rushed on to the market, after Pharmac did a deal with drug company Boehringer Ingelheim worth more than $100 million, making it freely available since July.

Pradaxa is registered in New Zealand only for patients with the heart rhythm disorder atrial fibrillation but haematologists are concerned that GPs and cardiologists are prescribing it for other conditions and to frail elderly with replacement heart valves and poor kidney function.

Pharmac has introduced the drug without a special authority restriction, meaning clinicians can prescribe it for any indication.

The Pradaxa website clearly states that it is used to reduce the risk of stroke and blood clots in people with atrial fibrillation not caused by a heart-valve problem, and that the risk of bleeding is higher in patients over 75, those with kidney problems and stomach ulcers. New Zealand haematologists have also discovered that people who are severely underweight may react badly to it.

Yet there is evidence that people who fit those categories are being prescribed Pradaxa. A Hawke's Bay family is grieving the death of their 92-year-old mother, who passed away two weeks ago. They asked that her name be withheld.

The woman had been taking warfarin without any problems for 20 years. "In July she was suddenly told she'd be taken off warfarin and instead would be taking Pradaxa," her daughter says. "I wondered about the wisdom of this at the time but didn't query it."

The woman was prescribed Pradaxa by her GP despite having two heart-valve replacements and being under 50kg. She began experiencing back pain, had trouble swallowing (a known side effect) and lost her appetite. She went back to her doctor and was given Gaviscon for indigestion.

"I thought, 'If you've just put someone on a new drug, why would you not relate it back to the possibility it could be a side effect of that?"' the daughter says.

Her mother was admitted to hospital and was found to have gastric bleeding and pneumonia. She was sent home but had a stroke and died the next day. The cause of death was given as a combination of gastric bleeding, pneumonia and heart disease.

The daughter says she wants to know more about what role Pradaxa played in her mother's death.

"I really wonder why they would take someone of this age off medication that seemed to have worked fine and put her on this one which has some potentially alarming side effects and has been released on to the market without much trial.

"Old people think doctors are God and they'll swallow anything they're given. This is being trumpeted as a wonder drug."

Muriel O'Neale of Masterton says Pradaxa should never have been released on to the market. Her 85-year-old husband Reg was in hospital with breathing difficulties when doctors decided to switch him from warfarin, which he had taken successfully for many years, to Pradaxa. That was on July 11 – by September 2 he was dead.

Muriel says Reg was in poor health and probably didn't have much longer to live, but his condition deteriorated rapidly on the new medication and made his final weeks extremely uncomfortable.

"Right from the start I didn't like it, there was something about it, Reg went down so quickly."

She said he was hallucinating, and had rectal bleeding. "He said to me, 'They've put a nappy on me 'cos I'm bleeding internally'. He was crying and upset."

Muriel says she suggested to her GP that Reg's symptoms might have been caused by Pradaxa as they matched symptoms she had read about. "He said: 'No, it wouldn't be this pill."'

She says clinicians seem to know little about Pradaxa's side effects.

"I asked one of the girls at the lab – she said 'we know nothing about it'."

Palmerston North haematologist Paul Harper is cataloguing adverse reactions to Pradaxa for health authorities and Boehringer Ingelheim, which is continuing its safety studies.

Harper says it is not possible to compare the number of people who have had bleeds on warfarin to those on Pradaxa, as figures have not been kept for warfarin.

He says Pradaxa has a lot of potential.

"I think it's a pretty good drug, if you're under 75 and you've got good kidneys. I guess my message would be you should be more cautious in older patients. I don't know why there's quite such an enthusiasm to change.

"If you're old, the data doesn't really support that it's a much better drug than warfarin, so if you're well controlled on warfarin you have to be questioning, should you be changing? That's something doctors should be doing with each patient: what are the benefits of going on this drug, and what are the risks? It's a bit unusual to change someone who's OK on the drug they're on."

Rob Creek, Boehringer Ingelheim's New Zealand medical director, says Harper was "absolutely right" in urging caution with elderly patients.

"Whenever you launch a new medicine it is always a major issue to make sure the practitioners are as educated as can be, especially when the medicine has an established and well-known risk of bleeding."

Creek says the company expected to see reports of bleeding but clinical trials showed the risk was less than that caused by warfarin.

"We knew this was going to happen ... it's not surprising. When you get a new drug launched there's a heightened awareness of the need to report adverse events – I think that's what we're seeing. It's not out of the ordinary I don't think, but we're watching carefully."

Thames woman Sheila Busby, 79, switched from warfarin to Pradaxa on the advice of her GP but has gone back to warfarin. She took 17 of the 60 capsules and quickly started having side effects, including rectal bleeding.

"My breathing got worse, I couldn't face food, I felt so listless – not an atom of energy. I felt that I didn't have control over my own mind – that's how it seemed to affect me. I just felt as if my mind was going, it was the most peculiar sensation."

Yet others wrote to extol Pradaxa's virtues.

A heart patient who has changed from warfarin wrote: "So far the only side effects I have felt is that I have a great deal more energy with additional motivation to do things. I do not feel anywhere near as tired and weak as I did."

WARFARIN v PRADAXA

WARFARIN: Known by the brand name Marevan, warfarin has been around for about 50 years, initially as a rat poison. It is used to treat leg clots, lung clots, to prevent clots with artificial valves and stroke in atrial fibrillation. Can be used after heart attacks. Pharmac says about 56,000 Kiwis take warfarin. It is difficult to tolerate for some and is associated with risks of strokes or bleeding if not closely managed. It requires careful monitoring, including regular blood tests and dose adjustments. Its levels are also affected by food containing vitamin K, such as broccoli and other green vegetables, which patients are advised to avoid. The effects of warfarin can be reversed in the event of a bleed by administering vitamin K.
It is distributed in New Zealand by GlaxoSmithKline.

PRADAXA: With the generic name dabigatran, Pradaxa is a new generation blood-thinning drug with the advantage of not requiring ongoing blood tests. However, there is no antidote in the event of a bleed.
In a trial of about 18,000 patients in 44 countries with the heart rhythm disorder atrial fibrillation, Pradaxa came out on top. At its lower dose, it was linked to similar rates of stroke as warfarin, but lower rates of major bleeding. At the higher dose, it was linked to fewer stroke but similar rates of major bleeding. However, a larger number of participants in the trial who were taking Pradaxa pulled out because of gastrointestinal symptoms such as pain, vomiting and diarrhoea. About 9000 New Zealanders have started Pradaxa since it was fully funded by Pharmac in July. The drug is registered here only for people with atrial fibrillation.
It is manufactured by the German company Boehringer Ingelheim.

MORE INFO

Medsafe advises patients with atrial fibrillation they are at risk of having a stroke and should not stop taking their medicine. If they have concerns, they should discuss them with their health professional. General inquiries can also be made on Healthline, 0800 611-116.

More information on Pradaxa is available at www.pradaxa.com and www.medsafe.govt.nz

Patients and health professionals who want to report an adverse reaction to Pradaxa (dabigatran) should contact the Centre for Adverse Reactions Monitoring (CARM) in Dunedin on (03) 479-7247 or by completing the reporting form on the CARM website at https://nzphvc-01.otago.ac.nz/carm-adr/

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