Kava practitioner alert

The Therapeutic Goods Administration (TGA) alerts health professionals to emerging concern about medicines containing kava (also known as kava kava or Piper methysticum) following international reports linking use of medicines containing this substance with hepatotoxicity.

There have been no Australian cases of liver failure or related problems due to kava-containing medicines reported to the Adverse Drug Reaction Unit of the TGA. However, the TGA is working with international regulatory bodies to determine the extent to which kava-containing medicines can be implicated as the cause of hepatotoxicity. To assist the TGA in determining whether there is a problem with kava-containing medicines in Australia, health practitioners are requested to review cases of unexplained hepatotoxicity to determine if any may be related to the use of these medicines.

Reports from Germany and Switzerland have linked kava extracts with 30 serious cases of hepatotoxicity, including six cases of liver failure resulting in one death, four cases requiring transplantation and one was under evaluation for transplantation at the time the report was published. The liver damage followed between two weeks to two years of use of kava-containing medicines. In a number of cases the causal link to kava was confounded by other factors such as concomitant drugs which themselves have previously been linked with liver problems. The products implicated in these reports are medicines which contain chemically extracted ingredients of kava as opposed to kava in herbal form (aqueous extract) prepared by traditional methods (as used for ceremonial and recreational purposes by Pacific Islander and other cultural groups).

Based on these adverse reports, some European countries have withdrawn or are proposing to suspend the marketing authorisation of certain kava-containing medicines. In some other countries manufacturers have either voluntarily withdrawn kava-containing medicines or health authorities have alerted health professional and consumers about potential liver toxicity problems with kava-containing medicines.

Kava-containing medicines are promoted for a variety of uses, including insomnia and sleeplessness, and relief of stress, anxiety and tension. The medicines are permitted to be marketed to all segments of the population except children under 12 and pregnant and nursing women. The TGA placed a limit on the maximum amount of Piper methysticum permitted per dosage form; for a tablet or a capsule, there is a limit of 125mg of kavalactones (a group of constituents found in Piper methysticum) and for a tea bag, there is a limit of 3g of dried rhizome (of Piper methysticum). In addition, all products containing Piper methysticum (any dosage form) must comply with a maximum daily dose of not more than 250mg of kavalactones. There are 84 medicines containing extracts from the kava plant on the Australian Register of Therapeutic Goods.

Kava is also a prohibited import under the Customs (Prohibited Imports) Regulations and requires an import permit before it can be imported into Australia and used in a listed therapeutic good.

Until the causal relationship between kava-containing medicines and liver toxicity is confirmed and until those patients most at risk are identified, the TGA urges you to remain vigilant in light of the overseas situation and to report any cases of hepatotoxicity that may be related to the use of medicinal products containing kava.

Practitioners are requested to consider asking patients presenting with liver-related symptoms about possible use of kava-containing medicines and to keep in mind that liver damage can also occur in the absence of obvious symptoms. Little is known about the way kava interacts with other medications.

The TGA is recommending that patients taking kava-containing medicines seek medical advice if they experience symptoms suggestive of liver injury. Consumers are being advised:

• to discontinue kava medications if symptoms appear and consult their medical practitioner;
• seek professional advice before commencing any kava-containing medicines; and
• to avoid kava-containing medications altogether if there are predisposing factors to liver damage, such as a history of liver disease.

Adverse reactions suspected to be associated with these products should be reported as soon as possible to the Adverse Drug Reactions Unit at the TGA using the postage pre-paid blue card or on 1800 044 114.