SHANGHAI - Three deaths caused by adverse drug reactions allegedly linked to use of herbal injection Shuanghuanglian have raised wider concerns over the safety of herbal injections in China.

The herbal injection is manufactured by the Duoduo Pharmaceutical Company in Northeast China's Heilongjiang province.

Plants including honeysuckle, scutellaria and forsythia are the major ingredients of shuanghuanglian. The herb has been widely used to allay fever, as well as treat upper respiratory tract infections, mild pneumonia and acute tonsillitis

Three patients in Anhui, Yunnan and Jiangsu provinces died between Sept 7 and 15, after receiving Shuanghuanglian injections. China's State Food and Drug Administration said in a statement that the three deaths were possibly linked to the use of the herbal injection.

"Shuanghuanglian has been widely used in China for a really long time," Huang Ting, Shanghai-based senior analyst with Sinolink Securities, told PharmAsia News. "The adverse reaction is probably related to poor production quality control of the manufacturer."

Shuanghuanglian is administered both orally and via injection, and tends to be more popular in rural areas, according to Huang. She said many companies have SFDA production approvals for Shuanghuanglian injection, but most are small companies.

According to SFDA, as of February, there were 21 manufacturers of Shuanghuanglian injection in China including Duoduo.

Following the deaths, SFDA and the Ministry of Health jointly suspended the sale and use of the herbal injection, and the two agencies set up a team to investigate the deaths.

The Heilongjiang provincial FDA said that the Duoduo Pharmaceutical Company had been ordered to stop producing its medicine, and hospitals are being urged to stop using the injection. The provincial authorities also started a probe into the production, testing and sales of the herbal injection.

SFDA Questions Safety Of Herbal Injections

SFDA began a national campaign in July to reevaluate the safety of all herbal injections in the country. Of the total 143 products, Shuanghuanglian and Shenmai injections are listed as the first batch for reassessment (PharmAsia News, July 27, 2009).

SFDA Deputy Director Wu Zhen said the agency would focus on safety assurance and carry out the work on three levels - risk inspection, comprehensive evaluation and standards elevation.

"While SFDA has released the notice on TCM injection safety rectification, due to the outbreak of A/H1N1 there is no further [action] yet," said Huang.

In February, the first death linked to the use of Shuanghuanglian injection was reported in Qinghai province, which was manufactured by Heilongjiang Wusuli Pharmaceutical Jiamusi Branch. The factory was shut down following the death.

Later in May, the National Adverse Drug Reaction Monitoring Center raised a medical alert on serious adverse reactions of levofloxacin and Shuanghuanglian injection.

SFDA figures show that roughly 120 herbal injections are available in China, accounting for about 3 percent of the total 4,000 medications in the country. About 70 percent of the adverse drug reactions in China are related to herbal injections.

Xi'an Jiahui Pharmaceutical in Northwest China was temporarily shut down in May while authorities investigated claims that its herbal injection Shenkang caused chills and high fever in some patients.

Shenkang is an injection composed of rhubarb, astragalus, red sage root and safflower for treating chronic renal failure.

Last October, a bacteria-contaminated Ciwujia herbal injection composed of Manyprickle Acantopanax Root made by another Heilongjiang-based company, to treat thrombosis and heart disease, killed three people and seriously injured four in Yunnan province. A man was sentenced to eight years in jail for selling the contaminated Ciwujia injections.

In the same month, a Yinzhihuang injection produced by a Shanxi company caused the death of a newborn baby and had adverse effects on three other infants. The injection is composed of gardenia and honeysuckle, which is used to treat liver disease and infantile jaundice.

"In China TCM injection manufacturers are under poor production conditions, and most of them are relatively small," said Huang, "Quality control of those factories is not strict enough."

When Big Means Safer

"Some big pharmaceutical companies also manufacture TCM injections but not many adverse reactions occur … because they are capable of better quality control," she added.

Huang said there is a weakness in the supply chain because local manufacturers are not able to manage the distribution and marketing by themselves.

"They don't have their own sale forces, and they have to rely on distributors to sell products to hospitals," said Huang, "Therefore they cannot control any problem that might happen in pharmacology, toxicology and adverse reactions."

"Big pharmaceutical companies, with their own sale forces, can get feedback about adverse effects immediately and ensure better drug safety," Huang added.

China's newly released Essential Drug List includes 102 TCMs (Also see "China Releases First Part Of Essential Drug List For Community Health Clinics And Rural Hospitals" - Scrip, 19 August, 2009.).

In an effort to partner with manufacturers to elevate the quality of traditional Chinese medicines sold in the U.S. and worldwide, the United States Pharmacopeial Convention recently verified for the first time ever one of the ingredients used in these medicines (Also see "U.S. Pharmacopeia Verifies Quality Of First Traditional Chinese Medicine Ingredient Under Voluntary Program" - Scrip, 3 September, 2009.)

- Ying Huang (pharmasianews@elsevier.com)

Safety Of Traditional Chinese Medicine Injections Questioned Following Three Deaths

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