by Eric Brand

Recently, I saw a very interesting article that was forwarded by our exceptional Belgian colleague, Tom Verhaeghe. The article discusses statistics on Chinese herbal medicine collected by Taiwan's national insurance, which provides 96% of the population with coverage for granule preparations of Chinese medicine. The article, which can be accessed at http://www.cmjournal.org/content/3/1/13, assesses the frequency of use of medicinals that either contain aristolochic acid (AA) or may be confused with AA-containing substitute species.

The data is quite comprehensive, and focuses on the use of medicinals that contain or may contain AA during the period of time between 1997 and 2003; in 2003, most AA-containing herbs were banned in Taiwan. The article is full of interesting statistics, a few of which I'd like to highlight here.

...

It should be noted that all of the AA-containing products in this study are no longer permitted in Taiwan by law, with the exception of xi xin, which is produced without AA. Nowadays, the correct identification of items like fang ji, mu tong, and mu xiang is rigorously maintained by strict GMP manufacturing laws. However, this study shows us very interesting information on prescribing trends before the AA issue was as well-known and well-managed as it is today.

The study analyzes the usage of medicinals that contain or may contain AA, specifically medicinals derived from Aristolochia spp. plants (tian xian teng, ma dou ling, and xi xin). It should be noted that xi xin can be produced in an AA-form by using only the roots, which lack AA. This is the dominant product in Taiwan now, but use of the whole plant was more common at the time of the study period.

The study also assessed usage data on fang ji, mu tong, and mu xiang, which may be confused with the AA-containing medicinals guang fang ji, guan mu tong, and qing mu xiang. These latter three substitute medicinals are banned for use now, but they were potentially on the market during the 7-year period of the study.

Some interesting highlights:

18,019 Chinese herbal products were licensed during the study period, of which 9,837 were covered by the national health insurance. Of the products covered by the national insurance, approximately 12% contained medicinals that posed a risk for AA, with mu xiang (35.3%) and xi xin (30.7%) being the most prevalent.

A total of 526,867 incidences of prescribed and government-reimbursed use of potentially AA-containing medicinals were recorded.

Among all the "potential risk" items, xi xin was the most frequently prescribed (44.7%).

The medical records of a 200,000 patient sample were randomly selected and analyzed for the study. "During the study period, 105,737 patients (52.9%) sought Chinese medicine treatment on at least one occasion, of which 78,644 were prescribed with AA-CHPs" (Chinese herbal products that pose a risk of AA).

97% of the patients given "at risk of AA-medicinals" were prescribed them for under one week.

90.7% of the medicines that contained "at risk of AA-medicinals" were prescribed as part of a whole compound formula. This reflects the Taiwanese style of prescribing granules by mixing whole formulas and adding singles rather than primarily building formulas from single-herb extracts.

The three most common formulas containing at risk items were: long dan xie gan tang (with mu tong), chuan xiong cha tiao san (with xi xin), and shu jing huo xue tang (with fang ji).

More than 70% of patients were exposed to lower cumulative doses of the at-risk AA herbs, and about 7% of the patients were prescribed xi xin, mu tong and ma dou ling in cumulative doses over 100 g. The study states: "Given that the random sample of this cohort accounts for approximately 1% of the population of Taiwan, it may be inferred that about 344,300 people were exposed to such high cumulated doses of Xixin, while about 234,700 people were exposed to similarly high cumulated doses of Mutong."

In the year after the ban, the researchers found a total of 68 cases banned herbs. Banned herbs were given to 25 patients by 19 Chinese medicine practitioners (in 19 clinics). Thus, the researchers estimate that about 2,760 patients in Taiwan received banned herbs during the first year after the ban.

At present, I am helping my teachers Nigel Wiseman and Chang Hen-Hong, the director of the Chinese medical departments at Chang Gung University and Chang Gung Hospital in Taiwan, to coordinate an herbal safety database project with the NIH (National Institute of Health). Dr. Chang created Taiwan's adverse event reporting system, and the NIH grant is allowing us to bring the Taiwanese adverse event reports to the English-speaking world for the first time.

After reading this article, I am particularly keen to see how many adverse events were reported from the use of these medicinals. It would be particularly interesting to see the degree to which discontinuing the use of AA-containing medicinals affects the number of adverse events reported.

I'll be sure to blog as I start to see more of the case reports from the Taiwan ADR reporting system. Maintaining access to medicinals is essential for the Chinese medical community here in the US. Amassing evidence-based safety data by analyzing total volume of usage relative to adverse events is an important aspect of protecting our access to Chinese medicinals. Overall, Chinese medicine is quite safe in terms of adverse event prevalence, so bringing more data to the Western community should help our efforts.

Big thanks to Tom for sharing the article!