By Ned Stafford

FRANKFURT, Germany (Reuters Health) – A group of pharmaceutical companies has appealed a preliminary decision by the German Federal Institute for Drugs and Medical Devices (BfArM) to ban the sale of the over-the-counter herbal medicine kava except in products that contain only minute amounts.

The BfArM in November announced the decision after studying 24 reports of severe liver toxicity with suspected links to consumption of kava, a substance also known as kava kava or Piper methysticum that has become increasingly popular in the US and Europe as a sedative, muscle relaxant and diuretic. The toxicity in some cases caused hepatitis, cirrhosis and liver failure, according to the reports, which also state that one person died and three underwent liver transplants.

Meanwhile, the US Food and Drug Administration (FDA) on Wednesday made public a "Dear Doctor" letter stating that, as a result of the adverse event reports accumulating in Europe, the US agency has begun its own investigation into kava.

The FDA asked doctors and other health professionals to review their cases of liver toxicity "to determine if any may be related to the use of kava-containing dietary supplements." The agency noted that it has received "several reports of serious injury allegedly associated" with the products, "with at least one report of hepatic failure requiring liver transplantation in a previously health young female."

The letter points out that Swiss regulatory authorities have already banned products containing a kava extract associated with similar adverse events.

In Germany, the appeal to the proposed ban on all kava extract-containing products was launched by nearly 50 companies via the German Medicines Manufacturers' Association (BAH).

Bernd Eberwein, executive director of the Bonn-based BAH, told Reuters Health that the 75-page appeal outlines in detail the manufacturers' contention that kava poses no threat of severe side effects at recommended dosages. "My opinion is that kava kava should not be removed from the market," he said.

He estimated retail sales of kava in Germany at between 50 million and 60 million German marks.

The appeal contends that there is no evidence to link the 24 cases of severe side effects cited by the BfArM to kava products, he said. For example, the person who died was an elderly woman already suffering from a variety of complications with "significant risk factors," he said. "There was no evidence that kava kava caused that death."

However, he conceded that higher dosages could increase the risk of side effects. "A majority of experts say the potential side effects are dose-dependent," he said, pointing out that even aspirin taken at high dosages can have negative effects.

Most manufacturers advise a daily intake of 60 to 120 mg of kave pyron, the active ingredient in kava products, Eberwein said, but doctors sometimes recommend larger doses of up to 240 mg. Three of the four people who have had liver transplants are believed to have exceeded a daily dosage of 240 mg, he said.

As for minor side effects, nearly 100 are possible with kava, including upset stomach, diarrhea, headache and a bad taste in the mouth, he said. "You have side effects with every medicine on the market," he stressed.

Eberwein said that banning the sale of kava would be excessive. However, manufacturers would be amenable to posting stronger warnings against high dosages and potential side effects, he said.

One industry representative who declined to be named said his first choice would be for continued over-the-counter sales of kava products, but that the industry might be willing to see them regulated as prescription drugs if that were the only choice.

Ulrich Hagemann, deputy head of BfArM's pharmacovigilance unit in Bonn, said that if the manufacturers' current appeal fails, they will have the opportunity to file one additional appeal with BfArM. If that appeal also is unsuccessful, they will be forced to appeal to the courts, he said.

German drugs group Merck KGaA earlier this year withdrew two over-the-counter drugs that contained kava due to safety concerns about the ingredient. The products, kavadura 120 mg and Kytta-Kava, had been sold as relaxation aids.