Aristolochia alert for practitioners

Introduction

The Therapeutic Goods Administration (TGA) would like to bring to your attention important safety information about botanical products containing Aristolochia species. We ask that you share this information with members of your professional association and other interested parties.

The TGA, along with overseas regulatory agencies, remains very concerned about Traditional Chinese Medicine (TCM) herbal products worldwide that are known to contain, or suspected to contain, Aristolochia species. These species of herbs, and a small number of other herbs, may contain aristolochic acids that are associated with severe kidney damage (1) and urinary tract cancer (2).

Most of the herbal products found to contain aristolochic acids have contained these acids because certain species of Aristolochia have been substituted for other species. These other species belong to the following genera:

Akebia, Asarum, Bragantia, Clematis, Cocculus, Diploclisia, Menispernum, Saussurea, Sinomenium, Stephania, Vladimiria

The particular species from these genera are listed in the Attachment to this practitioner alert.

This list is made up of three groups of herbal products as follows:

• Botanicals known or suspected to contain aristolochic acid (Group A);
• Botanicals which may be adulterated with aristolochic acid*(Group B); and
• Products which have Mu Tong and Fang Ji as declared ingredients (Mu Tong and Fang Ji are TCM names for products which may contain Aristolochia species) (Group C).

* There is unintended inclusion of Aristolochia in some herbal medicines because of confusion created by the fact that some herbs are very similar either in name or in appearance. There is also the possibility that certain herbal ingredients may be interchanged as part of the practice of Traditional Chinese Medicine.

While the TGA continues a testing program for all products on the Australian Register of Therapeutic Goods (ARTG) which may contain aristolochic acids, there are other products which are for practitioner-only use, many in the form of raw herbs, that are not regulated by the TGA.

This practitioner alert is to inform practitioner groups and their members of the identity of herbal products or materials that are recognised as being at risk of containing Aristolochia species or the aristolochic acids. This information should be brought to the attention of all healthcare practitioners who might prescribe, dispense, administer or otherwise handle or use such herbal products or materials.

Healthcare practitioners are asked to take extreme caution in using herbal products, in raw or formulated form, if the name of any of the herb(s) appears on the attached list. If healthcare practitioners are uncertain about the identity and authenticity of any of the herbal materials or products on the attached list, they should consider discontinuing their use.

The TGA is not aware of any adverse reaction reports in Australia associated with the inadvertent administration of herbal products containing Aristolochia species, although serious adverse events have been reported in the international literature. Healthcare practitioners are encouraged to take a thorough patient history of use of traditional and other complementary medicines and dietary supplements, especially in cases of unexplained renal pathology. Adverse reactions suspected to be associated with herbal products or preparations may be reported to the Adverse Drug Reactions Unit at the TGA on 02 6232 8381.

Background

• All species of Aristolochia are prohibited for supply, sale or use in therapeutic goods in Australia under the Standard for the Uniform Scheduling of Drugs and Poisons (SUSDP). However, Aristolochia species are finding their way into other herbal-based TCM products, including herbs in raw form, because they are easily confused with other herbs by being very similar, either in appearance or in name, to some other TCM herbs.
• Such confusion has led to inadvertent administration of Aristolochia, with two very serious incidents overseas in recent years^{(1, 2)} raising international concern and calls for greater vigilance in preventing Aristolochia-containing products from reaching the market.
• In September 2000, following these incidents, one in 1993 in Belgium and the other in 1999 in the UK, the Therapeutic Good Administration (TGA) sampled implicated products on the Australian market. When aristolochic acids were detected in some products the affected batches were immediately withdrawn.
• Repeat testing of new batches of the products previously found to be contaminated was conducted by the TGA in April of this year. Again some products were found to contain aristolochic acids. All batches of the affected products were withdrawn from the market and, in addition, the products were cancelled from the ARTG.
• Consumers who may have taken these medicines should have been contacted by their prescribing healthcare practitioner. Consumers were also informed of the recall by the placement of advertisements in both English and Chinese language daily newspapers.
• International concern remains high over trade in herbal products that are at risk of unintentionally including Aristolochia species or the aristolochic acids. The TGA has recently worked with overseas regulatory agencies to identify which other species and products have the greatest potential of containing the toxic aristolochic acids. The list which is attached to this practitioner alert has been developed on the basis of these concerns and consists of species from 11 genera, which are thought to either contain aristolochic acids or which are at risk of being adulterated with Aristolochia species.
• The TGA considers it important to bring the matter to the attention of practitioner associations so that they may be aware of the potential concerns.

For further details on this matter please contact the TGA or view the TGA website as below:

Contact Officer: Dr John Hall, Office of Complementary Medicines Phone: 02 6232 8062
Website: www.tga.gov.au

Bibliography

1. Lord GM et al (1999) "Nephropathy caused by Chinese herbs in the UK". Lancet 354: 481 - 482.
2. Nortier JL et al (2000) "Urothelial carcinoma associated with the use of a Chinese herb (Aristolochia fangchi)". New England Journal of Medicine 342: 1686 - 1692.

Botanicals or products at risk of containing aristolochic acids

In this section: Group A - Botanicals known or suspected to contain aristolochic acid | Group B - Botanicals which may be adulterated with aristolochic acid | Group C - Products which have mu tong and fang ji as declared ingredients

Group C - Products which have mu tong and fang ji as declared ingredients

• Ba Zheng Wan
• Chun Yang Zheng Ji Wan
• Da Huang Qing Wei Wan
• Dang Gui Si Ni Wan
• Dao Chi Wan
• Dieda Wan
• Fu Ke Fen Quing Wan
• Guan Xin Su He Wan
• Ji Sheng Ju He Wan
• Kat Kit Wan
• Long Dan Xie Gan Wan
• Quell Fire
• Shi Xiang Fan Shen Wan
• Xin Yi Wan