Painkiller Prexige Recalled In Australia

A PAINKILLER used by 60,000 Australians has been ordered off the shelves after the deaths of two people.

The Therapeutic Goods Administration yesterday announced the urgent recall of the drug Prexige, used to treat osteoarthritis and acute pain. Patients using the drug, also known by its chemical name lumiracoxib, are advised to stop taking it immediately and ask their doctor for an alternative prescription.

The TGA made the decision after receiving reports of eight people who suffered serious liver reactions, including two deaths and two liver transplants. Six of the reports occurred since the beginning of July.

TGA medical adviser Rohan Hammett said in a statement yesterday the drug was being recalled to prevent further cases of severe liver damage.

"It seems that the longer people are on the medicine, the greater chance of liver injury," Mr Hammett said.

Australia is the first country in the world to withdraw the drug, which is produced by Novartis Pharmaceuticals. Novartis estimates the drug has been used by about 60,000 Australians.

It is not yet known whether the 50 other countries that sell the drug will follow suit. Prexige is still awaiting approval by the US Food and Drug Administration.

Prexige went on sale in Australia in November, 2005 and gained widespread use since being listed on the Pharmaceutical Benefits Scheme in August last year. At the time, patients were warned to exercise caution with Prexige because it belonged to a family of drugs known as Cox-2 inhibitors linked with heart attack and stroke.

Cox-2 inhibitors, dubbed "super aspirin", have been under a cloud since a popular painkiller Vioxx was withdrawn in 2004 for increasing the risk of cardiovascular disease. Australia's National Prescribing Service - an independent, government-funded agency that advises doctors about the safe use of medications - warned last year that not enough was known about the long-term safety of Prexige.

Novartis spokeswoman Rebecca Fisher-Pollard urged people who used the drug not to panic. She said liver damage was known as a possible side effect but the incidence was rare.

"The information has always been there," Ms Fisher-Pollard said.

Novartis has set up a patient helpline to answer queries. Patients are advised to return any unused Prexige tablets to their pharmacist, who will give them a full refund. All GP groups and pharmacists have been alerted about the drug recall.

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Obesity From Liver Defect

Scientists at the Monell Chemical Senses Center have identified a genetically-transmitted metabolic defect that can lead to obesity in some individuals. The defect involves decreased production of liver enzymes needed to burn fat and may help to explain why some people become obese while others remain thin.

The global obesity epidemic is believed to be caused in part by the increased availability and intake of high calorie foods rich in fat and carbohydrates. These foods promote weight gain in humans and other animals, leading to a diet-induced obesity. The propensity to gain weight and become obese when consuming a high-fat diet is at least partially controlled by genes.

Results of this study help explain the interaction between genes and diet that underlies diet-induced obesity, comments senior author Mark Friedman. They also point to a way to identify individuals at risk for dietary obesity, perhaps even during childhood before the development of unhealthy eating habits.

The current study, reported in the recent issue of Metabolism, demonstrates that genetic susceptibility to diet-induced obesity is due to a reduced capacity to burn fat.

Fat is one of the fuels that the bodys cells burn to provide energy. This process, known as fat oxidation, takes place inside mitochondria, the cells power plants for generating energy.

If the ability to oxidize fat is impaired, the bodys capacity to make energy is reduced. This leads to increased hunger and overeating, as the body tries to increase the amount of energy available to meet its needs.

When the diet is low in fat, a reduced ability to burn fat has relatively little impact on energy production. However, if fat oxidation is impaired and the diet is high in fat, a greater proportion of calories cannot be used and food intake increases to cover the energy deficit. Because fat fuels are stored in fat tissue when theyre not oxidized, the increased food intake causes weight gain.

To determine whether preexisting differences in fat oxidation might contribute to individual susceptibility to diet-induced obesity, Friedman and lead author Hong Ji used rats that differ in their genetic predisposition to gain weight and become obese when fed a high-fat diet.

The closely-related strains weigh the same and eat the same amount of calories when fed a low-fat diet. However, when switched to a high-fat diet, the strain that is obesity-prone overeats and becomes obese, while the obesity-resistant strain does not.

The scientists observed that even when eating a low-fat diet and still lean, the obesity-prone rats were less able to burn fat than were the obesity-resistant rats. This intrinsic deficit in fat oxidation was linked to a decrease in the capacity to make two liver enzymes. One, CD36, is responsible for transferring fat fuels into liver cells, while the second enzyme, acyl-coenzyme A dehydrogenase, begins the oxidation process in mitochondria.

When fed a high-fat diet, the obesity-prone rats overate and became obese, gaining 36% more weight than resistant animals. Fat oxidation was further compromised due to a decreased ability to make CPT1A, the liver enzyme responsible for transporting fat into mitochondria.

The inherited propensity to gain weight when eating a high-fat diet appears to be due to a preexisting limit on the ability to burn fat in the liver. This defect persists during the development of obesity and is then further compounded by additional deficits in the fat oxidizing machinery, comments Friedman.

Other studies in Friedmans laboratory have demonstrated that a decrease in fat oxidation and energy production in the liver generates a signal that stimulates eating. Experiments in his and other laboratories have also observed that therapys that increase fat oxidation reduce food intake and cause weight loss in obese rodents.

With this in mind, Friedman notes, The present findings point to fat oxidation in the liver as a target for the development of drugs that suppress appetite and promote weight loss in obese individuals.

Future studies will guide development of such interventions by examining more closely the function and activity of the target enzymes.

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