Pradaxa linked to 280 deaths by medical journal, but regulator says the studies have not revealed ‘anything new’
Australia’s peak drug regulator said it will not be revising its safety advice for an anti-stroke medication associated with 280 deaths and 1,400 adverse drug reactions over the past five years, despite consumers health groups calling for a safety review.
It comes as Australia’s largest professional organisation for general practitioners said it had concerns about the aggressive marketing tactics used by the drug’s manufacturer as far back as 2010.
The Therapeutic Goods Administration (TGA) confirmed the blood-thinning medicine, Pradaxa, had been associated with the deaths, as well as side-effects including internal bleeding and heart attacks.
However, a spokeswoman said a series of papers recently published in the British Medical Journal had revealed nothing new about the drug.
She added that there had only been seven deaths from the drug in the four months to April this year, indicating deaths associated with the drug were decreasing as doctors became more familiar with it and how to best prescribe it.
The BMJ found the manufacturer of the drug, Boehringer Ingelheim, had withheld important data from drug regulators about its safety.
An investigation by the Journal revealed the benefits of monitoring blood levels of the drug in patients to help reduce the risk of major bleeding in patients taking the drug was not given to drug regulators when they were considering whether to approve it.
But Pradaxa was strongly marketed for being superior to its predecessor, Warfarin, because Boehringer Ingelheim claimed that unlike with Warfarin, patients would not need to undergo frequent blood tests and doctor visits to monitor their response.
President of the Royal Australian College of General Practitioners, Liz Marles, said the College was concerned back in 2010 when Pradaxa was being strongly promoted to doctors despite not yet having gained subsidy approval by the government’s Pharmaceutical Benefits Advisory Committee at the time.
The College was particularly worried because internal bleeding associated with the drug was difficult to reverse. In Warfarin, however, bleeding can be reversed with vitamin-K treatment.
“The way this drug was launched, with drug companies promoting it quite heavily before it received listing, set a precedent the College was concerned about,” Marles said.
“We were concerned with the issue of not being able to reverse the drug, a safety concern that was difficult to assess when it hadn’t yet been prescribed widely.”
Also before the drug had been approved for subsidy, Boehringer Ingelheim began offering it to patients for free, forcing the company to deny the scheme known as a patient familiarisation program was intended to put pressure on the federal government.
The TGA spokeswoman added that three deaths were associated with Warfarin in the same period though it was not possible to meaningfully compare the numbers of adverse events between Warfarin and Pradaxa, as Warfarin was a well-established medicine.
“Reporting rates for adverse events of well-established medicines are known to be lower than reporting rates for adverse events for a newer medicine,” she said.
About 30,000 patients take Pradaxa, while about 2.7 million scripts are written for Warfarin in Australia each year.
Risk factors for bleeding in patients using the drug include being aged 75 or over, having moderate kidney impairment or being on certain other medications.
In May, it was reported that the drug company would pay US$ 650 million (AU$ 696) to settle 4,000 US lawsuits over the drug.
Consumers Health Forum chief executive, Adam Stankevicius, said the reports in the BMJ underlined the need for drug companies to inform regulators and consumers fully about the risks of new drugs.
“From the BMJ article there was not the level of disclosure of the need for blood tests that it now appears are necessary for this drug,” he said.
“We call on the Therapeutic Goods Administration to undertake a thorough review of evidence given in relation to this drug.”
However he also warned patients not to stop taking their medications.
“Patients using Pradaxa should consult their doctors,” he said. “Pradaxa is an effective treatment, with some advantages over warfarin, according to the evidence available.“
A BMJ columnist and senior research fellow at Bond University’s faculty of health sciences in Queensland, Ray Moynihan, said the BMJ investigation had highlighted the failure of marketing self-regulation by the pharmaceutical industry.
“I think that the lack of genuine regulation in the marketing of pharma is a public health problem,” Moynihan, a researcher of pharmaceutical marketing and overdiagnosis, said.
“With this case we saw people die and we saw large numbers of adverse events.
“Of course such effects are a reality of potent drugs and people with genuine health problem,s but when we’re dealing with products that can be lifesaving or fatal surely its reasonable to have a much tougher regulation system when it comes to their marketing.”
But the manufacturers of Pradaxa told the ABC that they never withheld data from regulators and that their evidence did not support blood monitoring.
In a separate statement the company said it stood behind the safety and efficacy of Pradaxa.
“At Boehringer Ingelheim, patient health and safety is our top priority,” the statement said. “As a company with a deep heritage in, and commitment to, scientific innovation, we pride ourselves on ethical clinical research to produce new medicines that are safe and effective.”