Aristolochia alert for practitioners

Related information

23 July 2001

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:

* 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

Group A - Botanicals known or suspected to contain aristolochic acid
Genus Botanical Name Common or Other Names
Aristolochia Aristolochia spp. Aristolochia
Guan mu tong
Guang mu tong
Aristolochia acuminata Lam.
Syn. Aristolochia tagala Champ.
Oval leaf
Dutchman's pipe
Aristolochia argentina Griseb.
Aristolochia baetica Linn.
Syn. Aristolochia bracteolata Lam.
Aristolochia bracteata Retz. Ukulwe
Aristolochia chilensis Bridges in Lindl.
Aristolochia cinnabarina C.Y. Cheng & J.L. Wu
Aristolochia clematitis L. Birthwort
Aristolochia contorta Bunge Ma dou ling
Tian xian teng
Aristolochia cymbifera Mart. & Zucc. Mil homens
Aristolochia debilis Siebold & Zucc.
Syn. A. longa Thunb.
Syn. A. recurvilabra Hance
Syn. A. sinarum Lindl.
Ma dou ling
Tian xian teng
Qing mu xiang Seimokkou (Japanese)
Birthwort
Long birthwort
Aristolochia elegans Mast.
Syn. Aristolochia hassleriana Chodat
Aristolochia esperanzae Kuntze
Aristolochia fangchi Y.C. Wu ex L.D. Chow & S.M. Hwang Guang fang ji
Fang ji
Mokuboi (Japanese)
Kwangbanggi (Korean)
Fang chi
Kou-boui (Japanese)
Aristolochia fimbriata Cham.
Aristolochia indica L. Indian birthwort
Aristolochia kaempferi Willd.
Syn. Aristolochia chrysops (Stapf) E.H. Wilson ex Rehder
Syn. Aristolochia feddei H. Lév.
Syn. Aristolochia heterophylla Hemsl.
Syn. Aristolochia mollis Dunn
Syn. Aristolochia setchuenensis Franch.
Syn. Aristolochia shimadai Hayata
Syn. Aristolochia thibetica Franch.
Syn. Isotrema chrysops Stapf
Syn. Isotrema chrysops Stapf
Syn. Isotrema heterophylla (Hemsl.) Stapf
Syn. Isotrema lasiops Stapf
Yellowmouth
Dutchman's pipe
Aristolochia kwangsiensis Chun & F.C. How
Syn. Aristolochia austroszechuanica C. B. Chien & C. Y. Cheng
Aristolochia macrophylla Lam.
Syn. Aristolochia sipho L'Hér.
Dutchman's-pipe
Aristolochia manschuriensis Kom.
Syn. Hocquartia manshuriensis (Kom.) Nakai
Syn. Isotrema manchuriensis (Kom.) H. Huber
Manchurian birthwort
Manchurian
Dutchman's pipe
Guang mu tong
Kan-Mokutsu (Japanese)
Mokuboi (Japanese)
Kwangbanggi (Korean)
Aristolochia maurorum L.
Aristolochia maxima Jacq.
Syn. Aristolochia maxima var. angustifolia Duchartre in DC.
Syn. Howardia hoffmannii Klotzsch
Aristolochia mollissima Hance
Aristolochia pistolochia L.
Aristolochia rigida Duch.
Aristolochia rotunda Linn.
Aristolochia serpentaria L.
Syn. Aristolochia serpentaria var. hastata (Nutt.) Duch.
Virginia snakeroot
Serpentaria
Virginia serpentary
Aristolochia watsoni Wooton & Standley or
Aristolochia watsonii Wooton & Standley
Syn. Aristolochia porphyrophylla Pfeifer
Aristolochia westlandii Hemsl. or
Aristolochia westlandi Hemsl.
Aristolochia zollingeriana Miq.
Syn. Aristolochia kankauensis Sasaki
Syn. Aristolochia roxburghiana subsp. kankauensis (Sasaki) Kitam.
Syn. Hocquartia kankauensis (Sasaki) Nakai ex Masam.
Syn. Aristolochia tagala var. kankauensis (Sasaki) T. Yamaz.
Asarum Asarum canadense Linn.
Syn. Asarum acuminatum (Ashe) E.P. Bicknell
Syn. Asarum ambiguum (E.P. Bicknell) Daniels
Syn. Asarum canadense var. ambiguum (E.P. Bicknell) Farw.
Syn. Asarum canadense var. reflexum (E.P. Bicknell) B.L. Rob.
Syn. Asarum furcatum Raf.
Syn. Asarum medium Raf.
Syn. Asarum parvifolium Raf.
Syn. Asarum reflexum E.P. Bicknell
Syn. Asarum rubrocinctum Peattie
Wild ginger
Indian ginger
Canada snakeroot
False coltsfoot
Colic root
Heart snakeroot
Vermont snakeroot
Southern snakeroot
Asarum himalaicum Hook. f. & Thomson ex Klotzsch or
Asarum himalaycum Hook. f. & Thomson ex Klotzsch
Tanyou-saishin (Japanese)
Asarum splendens (F. Maek.) C.Y. Cheng & C.S. Yang Do-saishin (Japanese)
Bragantia Bragantia wallichii R.Br.
Specimen exists at New York Botanical Gardens.
Tropicos does not list this species as a synonym for any Thottea species. Kew Gardens Herbarium does not recognize the genera Bragantia. Until additional information is obtained we will use the name as cited in J.Nat. Products 45:657-666 (1982)
Group B - Botanicals which may be adulterated with aristolochic acid
Genus Botanical Name Common or Other Names
Akebia Akebia spp. Akebia
Mu tong
Ku mu tong
Zi mutong
Bai mu tong
Mokutsu (Japanese)
Mokt'ong (Korean)
Akebia quinata (Houtt.) Decne.
Syn. Rajania quinata Houtt.
Chocolate vine
Fiveleaf akebia
Mu tong
Yu zhi zi
Mokutsu (Japanese)
Akebia trifoliata (Thunb.) Koidz). Mu tong
Three leaf akebia
Yu zhi zi
Asarum Asarum forbesii Maxim. Batei-saishin (Japanese)
Asarum heterotropoides F. Schmidt
Syn. Asarum heterotropoides F. Schmidt
Syn. Asiasarum heterotropoides (F. Schmidt) F. Maek.
Keirin-saishin (Japanese)
Chinese wild ginger
Manchurian wild ginger
Bei xi xin
Xin xin
Asarum sieboldii Miq.
Syn. Asarum sieboldii fo. seoulense (Nakai) C.Y. Cheng & C.S. Yang
Syn. Asarum sieboldii var. seoulensis Nakai
Syn. Asiasarum heterotropoides var. seoulense (Nakai) F. Maek.
Syn. Asiasarum sieboldii (Miq.) F. Maek.
Usuba-saishin (Japanese)
Chinese wild ginger
Xi Xin
Hua Xi Xin
Manchurian wild ginger
Siebold's wild ginger
Clematis Clematis spp. Clematis
Mufangji
Clematidis
Ireisen (Japanese)
Wojoksum (Korean)
Clematis armandii Franch.
Syn. Clematis armandii fo. farquhariana (W.T. Wang) Rehder & E.H. Wilson
Syn. Clematis armandii var. biondiana (Pavol.) Rehder
Syn. Clematis biondiana Pavol.
Syn. Clematis ornithopus Ulbr.
Armand's clematis
Chuan mu tong (stem)
Xiao mu tong
Armand's virgin bower
Clematis chinensis Osbeck. Chinese clematis
Wei ling xian (root)
Clematis hexapetala Pall.
Clematis montana Buch.-Ham. ex DC.
Syn. Clematis insulari-alpina Hayata
Clematis montana Buch.-Ham. Ex DC.
Clematis uncinata Champ. ex Benth.
Syn. Clematis alsomitrifolia Hayata
Syn. Clematis chinensis var. uncinata (Champ. ex Benth.) Kuntze
Syn. Clematis drakeana H. Lév. & Vaniot
Syn. Clematis floribunda (Hayata) Yamam.
Syn. Clematis gagnepainiana H. Lév. & Vaniot
Syn. Clematis leiocarpa Oliv.
Syn. Clematis ovatifolia T. Ito ex Maxim.
Syn. Clematis uncinata var. biternata W.T. Wang
Syn. Clematis uncinata var. coriacea Pamp.
Syn. Clematis uncinata var. floribunda Hayata
Syn. Clematis uncinata var. ovatifolia (T. Ito ex Maxim.) Ohwi ex Tamura
Syn. Clematis uncinata var. taitongensis Y.C. Liu & C.H. Ou
Cocculus Cocculus spp. Cocculus
Cocculus carolinus (L.) DC.
Syn. Cebatha carolina Britton
Syn. Epibaterium carolinum (L.) Britton
Syn. Menispermum carolinum L.
Cocculus diversifolius DC.
Syn. Cocculus madagascariensis Diels
Cocculus hirsutus (L.) Diels
Syn. Cocculus villosus DC.
Syn. Menispermum hirsutum L.
Cocculus indicus Royle
Syn. Anamirta paniculata Colebr.
Indian cockle
Cocculus laurifolius DC.
Syn. Cinnamomum esquirolii H. Lév.
Cocculus leaebe DC.
Cocculus madagascariensis Diels
Syn. Cocculus diversifolius DC.
Cocculus orbiculatus DC.
Syn. Cissampelos pareira Linn.
Cocculus orbiculatus (L.) DC.
Syn. Cocculus cuneatus Benth.
Syn. Cocculus sarmentosus (Lour.) Diels
Syn. Cocculus sarmentosus var. linearis Yamam.
Syn. Cocculus sarmentosus var. pauciflorus Y.C. Wu
Syn. Cocculus sarmentosus var. stenophyllus Merr.
Syn. Cocculus thunbergii DC.
Syn. Cocculus trilobus (Thunb.) DC.
Syn. Menispermum orbiculatus L.
Syn. Menispermum trilobum Thunb.
Syn. Nephroia sarmentosa Lour.
Moku-boui (Japanese)
Cocculus palmatus (Lam.) DC. Columba
Columbo
Cocculus pendulus Diels
Syn. Cebatha pendula (J.R. & C. Forst.) Kuntze
Syn. Epibaterium pendulus Forst. f.
Syn. Cocculus Epibaterium DC.
Cocculus pendulus (Forst. & Forst.) Diels
Cocculus palmatus Hook.
Syn. Jateorhiza Miersii Oliver
Colombo
Cocculus thunbergii DC.
Diploclisia Diploclisia affinis (Oliv.) Diels
Syn. Diploclisia chinensis Merr.
Syn. Cocculus affinis Oliv.
Diploclisia chinensis Merrill Xiangfangchi
Menispernum Menispernum dauricum
Saussurea Saussurea lappa (Decne.) Sch. Bip. Mokkou (Japanese)
Sinomenium Sinomenium acutum (Thunb.) Rehder & E.H. Wilson
Syn. Cocculus diversifolius var. cinereus Diels
Syn. Cocculus heterophyllus Hemsl. & E.H. Wilson
Syn. Menispermum acutum Thunb.
Syn. Sinomenium acutum (Thunb.) Rehder & E.H. Wilson var. cinereum (Diels) Rehder & E.H. Wilson
Syn. Sinomenium diversifolium (Diels) Diels
Orientvine
Xunfengteng
Dafengteng
Daqingmuxinag
Zhuigusan
Da ye qingshener
Mufangji
Hanfangji
Tuteng
Zhuigufeng
Maofangji
Stephania Stephania spp. Stephania
Stephania tetrandra S. Moore Fen fang ji , fang ji
Fang ji (root)
Han fang ji
Kanboi (Japanese)
Hanbanggi (Korean)
Fun-boui (Japanese)
Vladimiria Vladimiria souliei (Franch.) Ling Sen-mokkou

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