Wednesday, August 15, 2007

Banned drug was given in high dose

Now we hear it: Another case of regulatory failure

THE osteoarthritis drug withdrawn from sale on Saturday after the deaths of two patients was approved for use in Australia at double the dose allowed in more than 50 other countries. Australia is the only country in the world where patients have died while taking Prexige. The 200mg dose was approved by the Therapeutic Goods Administration in 2004 to treat osteoarthritis, while other countries recommend a 100mg dose.

The TGA received eight reports of liver damage, including two deaths and two patients who required liver transplants. Five of those were taking 200mg daily, one person was taking 200-400mg daily, one person 400mg daily and the TGA is yet to determine the dose for the eighth patient.

Doctors told The Australian yesterday that the recall highlighted the need for continuing trials into the safety of newly approved drugs. Prexige was first sold in Australia in November 2005 but it was not widely used until it was listed on the Pharmaceutical Benefits Scheme in August last year, despite concerns from medical groups about its safety.

Lynn Weekes, president of the National Prescribing Service -- an independent medication advisory agency -- said pharmaceutical companies should conduct "post-marketing" studies on new drugs, even after they won approval, to detect side-effects that become apparent only once a medicine is widely used. "There were studies done initially on Prexige with doses up to 400mg, and there was no evidence of liver damage," she said. "That's why post-marketing studies are really essential, not just in terms of a drug's safety but also usage."

The NPS warned last July that there was insufficient information about Prexige's safety to support its listing on the PBS. "We are warning all GPs that its long-term safety hasn't been proven yet," an NPS spokesman said at the time. Prexige, used by 60,000 Australians, was one of the new generation of painkillers, called Cox-2 inhibitors, thought to cause fewer side-effects, such as gastric bleeding, than other anti-inflammatory drugs such as ibuprofen and naproxen. However, the drugs fell out of favour in 2004 when pharmaceutical giant Merck withdrew Vioxx, a Cox-2 used to treat arthritis, after it was found to increase the risk of heart attack and stroke. In April 2005, drug company Pfizer withdrew its painkiller Bextra amid concerns that it also was linked to heart disease.

Dr Weekes said doctors were aware that Prexige belonged to a class of drugs linked to cardiac side-effects, but it was not known that they caused serious liver damage. "We were aware of cardiac risks associated with this class of drugs. But these effects in the liver have really come out of the blue," Dr Weekes said. A spokeswoman for Novartis, which makes Prexige, said liver damage was a rare side-effect of the drug. "Serious liver side-effects have been reported rarely, for all Cox-2s and non-steroidal anti-inflammatories. It is a known but rare side-effect for this class of drugs," she said. "What we found is that in a very short period of time, the adverse events that were reported were higher than we would expect, so we made the decision to withdraw the product."

The TGA approved the 100mg dose of Prexige last June.


Viruses that kill bacteria may help with MRSA

A type of “good” virus that infects and kills many types of harmful bacteria is being investigated by scientists in the fight against antibiotic-resistant superbugs such as MRSA. A cream containing the viruses, known as bacteriophages (phages), has been developed to eliminate hospital-acquired infections and could be available within three years. Similar treatments are also being developed for bacterial ear infections and food poisoning, which are triggered by the most stubbornly resistant bugs.

Despite having been used in the former Soviet Union and Eastern Europe to treat infections since the 1920s, the viruses have been neglected in the West for more than 60 years. Scientists are now re-examining whether phage therapies, previously considered to have been superseded by antibiotics, can curb overuse of the drugs. Clinical trials of the proposed cream for MRSA are planned next year after laboratory tests in which phages wiped out more than 15 strains of the superbug.

MRSA is one of a gathering army of microbes that are becoming immune to antibiotic medicines. Others include resistant strains of tuberculosis, the food bug Escherichia coli, and two more causes of hospital infections, Acinetobacter and Pseudomonas.

Contrary to current guidance to eliminate infections, which emphasises the importance of regular hand-washing and use of alcohol gels, the anti-MRSA cream could be applied to the inside of the nose, where bacteria are known to thrive. The cream is likely to contain a “cocktail” of three or four types of virus so that it is difficult for the bugs to build up resistance to it.

MRSA, or methicillin-resistant Staphylococcus aureus, is carried in the body of one in three people without any ill effects, but it can cause potentially lethal infections in hospitals, where sick people come into contact with those harbouring the bacteria. Latest figures show that there were 3,517 MRSA infections in British hospitals between October 2005 and March last year. Shedding of the bug from the nose is the main mode of transmission, researchers say. Treating the full range of hospital-acquired infections costs the NHS about 1 billion pounds a year.

Nick Housby, chief executive of the Coventry-based biotech company Novolytics, which is carrying out the research, said that the aim was to use the phage cream as a preventative measure that could be given to staff and patients a day or two before they go into hospital. But he added that it could also eliminate infections in affected patients within 24 hours. “We’re extremely optimistic,” he said. We know we can kill, in the laboratory, clinically relevant strains. It’s a question now of putting it into the right cream, in terms of the formulation, to make sure that it works.”

The cream would be applied with a stick inserted into the nose. The viruses could then target MRSA bacteria, injecting them with their own genetic material. The bugs are reprogrammed to produce more viruses, which then break out of their host, destroying it in the process. Since the viruses reproduce themselves, repeat treatments would not be needed as frequently as with antibiotics.

The viruses are now starting to make a comeback in the West, where more than 12 companies are now developing phage products. Geoff Hanlon, an expert in the viruses at the University of Brighton, said: “We’re now finding antibiotics are becoming less useful. The climate is probably right to revisit bacteriophage therapy.”



Just some problems with the "Obesity" war:

1). It tries to impose behavior change on everybody -- when most of those targeted are not obese and hence have no reason to change their behaviour. It is a form of punishing the innocent and the guilty alike. (It is also typical of Leftist thinking: Scorning the individual and capable of dealing with large groups only).

2). The longevity research all leads to the conclusion that it is people of MIDDLING weight who live longest -- not slim people. So the "epidemic" of obesity is in fact largely an "epidemic" of living longer.

3). It is total calorie intake that makes you fat -- not where you get your calories. Policies that attack only the source of the calories (e.g. "junk food") without addressing total calorie intake are hence pissing into the wind. People involuntarily deprived of their preferred calorie intake from one source are highly likely to seek and find their calories elsewhere.

4). So-called junk food is perfectly nutritious. A big Mac meal comprises meat, bread, salad and potatoes -- which is a mainstream Western diet. If that is bad then we are all in big trouble.

5). Food warriors demonize salt and fat. But we need a daily salt intake to counter salt-loss through perspiration and the research shows that people on salt-restricted diets die SOONER. And Eskimos eat huge amounts of fat with no apparent ill-effects. And the average home-cooked roast dinner has LOTS of fat. Will we ban roast dinners?

6). The foods restricted are often no more calorific than those permitted -- such as milk and fruit-juice drinks.

7). Tendency to weight is mostly genetic and is therefore not readily susceptible to voluntary behaviour change.

8). And when are we going to ban cheese? Cheese is a concentrated calorie bomb and has lots of that wicked animal fat in it too. Wouldn't we all be better off without it? And what about butter and margarine? They are just about pure fat. Surely they should be treated as contraband in kids' lunchboxes! [/sarcasm].

Trans fats:

For one summary of the weak science behind the "trans-fat" hysteria, see here. Trans fats have only a temporary effect on blood chemistry and the evidence of lasting harm from them is dubious. By taking extreme groups in trans fats intake, some weak association with coronary heart disease has at times been shown in some sub-populations but extreme group studies are inherently at risk of confounding with other factors and are intrinsically of little interest to the average person.


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