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Published: December 2012

Complementary Corner: Aristolochic Acid and Urothelial Cancer

Prescriber Update 33(4): 35
December 2012

Healthcare professionals are encouraged to ask patients about past use of traditional Chinese medicines, specifically medicines derived from Aristolochia species following reported cases of nephrotoxicity and carcinogenicity in Europe, China and Japan1. Products containing Aristolochia have been classified as human carcinogens by the International Agency for Research on Cancer as all Aristolochia plant species contain aristolochic acid2.

Recently, a study has linked the high rate of urothelial cancer of the upper urinary tract in Taiwan with the widespread use herbal medicines containing aristolochic acid3. In Taiwan, the incidence of urothelial cancer of the upper urinary tract is the highest reported anywhere in the world3. Due to the lifelong persistence of mutations caused by aristolochic acid, patients treated with Aristolochia are at risk of developing urothelial cancer of the upper urinary tract at any time in their life3.

This study in Taiwan is supported by research carried out in Belgium on patients who were inadvertently exposed to Aristolochia in weight loss pills4. Aristolochic acid was found to be associated with progressive interstitial nephritis in these patients leading to terminal renal failure4. Subsequently, a number of the patients being treated for terminal renal failure were found to have developed urothelial cancer5.

Despite being banned in many countries, it appears that many aristolochic acid-containing products are still available over the internet1,6. A report in the Medical Journal of Australia described a fatal case of a 75-year-old man with a three year history of using Chinese herbal medicines containing aristolochic acid6. The patient was diagnosed with renal failure and died four years after initial presentation6. Although Australia banned products suspected of containing aristolochic acid in 2002, the medicines had been obtained from outside Australia via mail order.

In 2003, Medsafe released an urgent product alert advising of the withdrawal from distribution in New Zealand of some traditional Chinese medicines after they were found to contain aristolochic acid7. This alert included a list of herbs which are commonly substituted with Aristolochia species, along with a list of products which have been tested and found to contain aristolochic acids.

References
  1. European Medicines Agency. 2005. Public Statement on the Risks Associated with the use of Herbal Products Containing Aristolochia Species. Doc Ref: EMEA/HMPC/138381/2005. URL: www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2010/04/WC500089957.pdf (accessed 16 November 2012).
  2. IARC. 2002. IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Humans: Some traditional herbal medicines, some mycotoxins, naphthalene and styrene. Lyons: IARC Press. URL: monographs.iarc.fr/ENG/Monographs/vol82/mono82-6B.pdf (accessed 16 November 2012).
  3. Chen CH, Dickman KG, Moriya M, et al. 2012. Aristolochic acid-associated urothelial cancer in Taiwan. Proceedings of the National Academy of Sciences of the United States of America 109: 8241-6.
  4. Vanhaelen M, Vanhaelen-Fastre R, But P, et al. 1994. Identification of aristolochic acid in Chinese herbs. Lancet 343: 174.
  5. Nortier JL, Martinez MC, Schmeiser HH, et al. 2000. Urothelial carcinoma associated with the use of a Chinese herb (Aristolochia fangchi). New England Journal of Medicine 342: 1686-92.
  6. Chau W, Ross R, Li JY, et al. 2011. Nephropathy associated with use of a Chinese herbal product containing aristolochic acid. Medical Journal of Australia 194: 367-8.
  7. Medsafe. 2003. Director-General's privileged statement under section 98 of the Medicines Act 1981. Media Release 21 January 2003. URL: www.medsafe.govt.nz/hot/media/media2003.asp (accessed 16 November 2012).
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