Zyban: new scrutiny after nine deaths
Health authorities are investigating the deaths of nine Australians to establish whether their use of the controversial anti-smoking drug Zyban was a contributing factor.
Unprecedented demand for the drug has been accompanied by a surge in the number of adverse reactions being reported.
More than 200,000 Australian smokers are believed to have taken Zyban, which helps to reduce their craving for nicotine.
The Therapeutic Goods Administration, recognised as one of the world's top regulatory authorities, has been monitoring the drug since its release here last November.
The administration now has reports of nine deaths of people who had been taking Zyban, including one who had stopped taking it before his death.
In addition to the reported deaths, there have been 400 to 500 adverse reactions - considered high - in the past six weeks alone.
"We are going to look at them (the adverse reactions) and see what has changed," John McEwen, director of the administration's adverse drug reactions unit told The Sunday Age.
Despite a doubling of the deaths - reported in The Age at four late last month - the administration does not regard the toll as excessive.
"The challenge there is to sort out whether that is coincidental or whether the drug might have played a role," Dr McEwen said.
"What we need to keep in mind is that the reason this drug is being used is because these people are smokers and that is a risk factor for some of the deaths. For example, the risk of a heart attack would be increased in the case of a smoker."
Demand for Zyban was so strong when it became available on the Pharmaceutical Benefits Scheme in February that the drug's manufacturer, GlaxoSmithKline, ran out of supplies for several weeks.
In Britain, Zyban has been linked to 37 deaths. The manufacturer has been criticised for failing to give doctors enough information, and has been ordered to clarify its advice to people using the drug in combination with other medicines.
An estimated 3.5 million Australians smoke and the cost to the country - including the provision of health care, loss of productivity, absenteeism - is conservatively put at $5.7 billion. Smoking kills more Australians than the combined deaths from road accidents, breast cancer, AIDS, suicide, murder and diabetes.
Dr McEwen emphasised that, at this stage, none of the nine deaths could be attributed to Zyban.
"No, I don't have any particular concern about this drug," he added.
However, he said that because of the high number of adverse reactions, the Adverse Drug Reactions Advisory Committee would discuss the drug at its regular meeting.
The reported adverse reactions to Zyban, which have included skin reactions, nervous system problems, psychological disturbances and gastro-intestinal illness, have been discussed at the committee's last two meetings.
The administration's investigation will examine all deaths, including autopsy and coroners' reports. "At the moment there is no common thread," Dr McEwen said. "The mode of death is different among those patients ..."
Investigators will also look at the national death statistics to develop some estimates of how many deaths might have been expected over the period that the nine died.
Dr McEwen explained that before a drug was marketed there was an assessment of its quality, safety and efficacy. By the time it won approval or registration, a decision had been made that, on balance, the benefits or efficacy had been demonstrated and the safety of the product, relative to the benefits, had been demonstrated.
"In the case of Zyban, we would say the great majority of the reports we are getting are consistent with the results we have seen in the clinical trials, or what might have been expected from our knowledge at the time.
"Insomnia was very common in the clinical trials. That was described, that was known, and it is in the prescribing information for doctors to read.
"The product clearly warns that if you have a seizure disorder - if you suffer from epilepsy - you must not take the drug. If you are taking another medicine known to lower your seizure threshold, the doctor should be very cautious in prescribing it."
In the clinical trials, 40 per cent of the patients on Zyban suffered from insomnia compared to 18 per cent in the placebo group; 9 per cent had disturbed concentration compared to 4 per cent in the placebo group. Two out of 100 patients reported having an itch. Two patients died during the trials but their deaths were assessed as not being related to the drug.
Asked to speculate on why Zyban had attracted such attention, Dr McEwen suggested the media attention before its launch had lifted people's expectations and they had lost sight of the fact that the drug might have some adverse effects.
The huge swell of British interest in the safety of the drug propelled the chairman of the government's Committee on the Safety of Medicines, Alasdair Breckenridge, to release a statement in which he claimed that the majority of patients who died while taking Zyban had underlying medical conditions.
Professor Breckenridge pointed out that about 2 per cent of adverse reports for all medicine were associated "with a fatal outcome" and that for Zyban it was less than 1 per cent.
He also said that smoking was the single greatest cause of premature deaths in Britain and was responsible for 120,000 deaths a year.
However, that did not stop a coroner, who investigated the death of 21-year-old flight attendant Kerry Watson who had been taking Zyban, from criticising GlaxoSmithKline for failing to give doctors enough information about the drug. He ordered the company to clarify its advice to people using the drug in combination with other medicine. Ms Watson had also been taking the anti-malarial treatment chloroquine at the time of her death.
Mike Devoy, medical director of GlaxoSmithKline in Australia, said the company was constantly in discussion with the Therapeutic Goods Administration to make the prescribing information as comprehensive as possible.
"From the company's perspective, we have no information to suggest that Zyban is the cause of deaths either here or in Britain," he said.
Zyban was originally developed as an anti-depressant in the 1980s. It was first launched in the US where a Los Angeles doctor, Linda Ferry, noticed that her patients who were taking the drug were losing their craving for nicotine. After some initial work, she brought her findings to the attention of GlaxoSmithKline.
"Because it acts on the central nervous system, it seems to reduce cravings for nicotine," Dr Devoy said. "It works on certain neurotransmitters and this is how it is thought to have its action in depression and also in smoking cessation."
Dr Devoy said the drug was not "a magic bullet" and had to be accompanied by a determination to quit the habit. Dr McEwen believed there was a greater desire to stop smoking in Australia than there was in the UK. That statement would be music to the ears of ASH, Action on Smoking and Health.
Its chief executive, Anne Jones, is quick to point to the alarming toll from smoking. For example, she said that 19,000 Australians died each year from smoking-related diseases, nearly 7000 of them from lung cancer. Nearly a million bed days were taken up by people with smoking related diseases, placing a huge burden on the hospital system.
Ms Jones said ASH supported any safe and effective treatment option to help smokers to quit, and she had no reservations about Zyban.
"Until John McEwen raises the alarm, I am going with his advice," she said.