Clinical

Arthritis 'medical food' Limbrel tied to liver injury

Last Updated: 2012-06-18 18:45:10 -0400 (Reuters Health)

By Amy Norton

NEW YORK (Reuters Health) - A "medical food" sold as an arthritis treatment may have caused four cases of acute liver failure, researchers reported Monday.

The product in question is called flavocoxid, sold under the brand-name Limbrel. It contains flavonoids, including catechins, which are best known as components of green tea.

Limbrel is considered a medical food. It is available by prescription only, to treat osteoarthritis. But medical foods in the U.S. don't have to be proven safe and effective before they're marketed.

In a report in Annals of Internal Medicine, researchers describe four cases in which Limbrel users developed abdominal pain, jaundice, pruritus, and fever, along with elevated liver enzymes. All four recovered after they stopped using the product.

The researchers cannot say with certainty that all four cases were caused by Limbrel.

"There's no single test you can do to say, 'Bingo, it's caused by this,'" said lead author Dr. Naga Chalasani, of Indiana University School of Medicine in Indianapolis.

But he said three of the cases were "highly likely" to have been caused by Limbrel. The fourth was "possibly" caused by the product.

Timing was a big clue. All four patients developed signs of liver toxicity within three months of starting the arthritis treatment. And all got better within three to 12 weeks of stopping it.

Scottsdale, Arizona-based Primus Pharmaceuticals, which makes Limbrel, did not return calls seeking a comment.

The four hepatotoxicity cases turned up as part of an ongoing surveillance study of liver injury caused by drugs or herbal supplements. Between 2004 and 2010, researchers at several U.S. medical centers enrolled 877 patients who were thought to have liver damage from a medication or supplement.

Four of those cases were linked to Limbrel.

It's not fully clear why the product would damage the liver. "That's the million-dollar question," Dr. Chalasani said.

But he and his colleagues suspect it may be the catechin content. Green tea extracts, which contain high concentrations of catechins, have been linked to liver toxicity.

Even if catechins are to blame, that still leaves the question of why only certain Limbrel users would develop liver problems. "There has to also be some kind of susceptibility" to liver injury, Dr. Chalasani said, noting that it could be a genetic vulnerability.

Also unclear is how many Limbrel users out there may have suffered liver injury.

Besides the four cases in this report, Primus has gotten eight reports of "clinically apparent" liver toxicity that the company shared with Dr. Chalasani's team.

The product is not widely used. Worldwide, it seems that about 400,000 prescriptions have been written for Limbrel, Dr. Chalasani noted.

SOURCE: http://bit.ly/PeuCrl

Ann Intern Med 2012.