United States Pharmacopeia review of the black cohosh case reports of hepatotoxicity.

OBJECTIVE Black cohosh [Actaea racemosa L., formerly Cimicifuga racemosa (L.) Nutt.] is a botanical used mainly for the management of menopausal symptoms. Recently, regulatory agencies in Australia, Canada, and the European Union have released statements regarding the "potential association" between black cohosh and hepatotoxicity. In response, the Dietary Supplement Information Expert Committee of the US Pharmacopeia's Council of Experts reviewed safety information for black cohosh products. DESIGN The Expert Committee analyzed information from human clinical case reports, adverse event reports, animal pharmacological and toxicological data, historical use, regulatory status, and contemporaneous extent of use. Reports were obtained from diverse sources, including the European Medicines Agency, Health Canada, the Australian Therapeutic Goods Administration, and the US Food and Drug Administration. Case reports pertaining to liver damage were evaluated according to the Naranjo causality algorithm scale. RESULTS Thirty nonduplicate reports on use of black cohosh products concerning liver damage were analyzed. All the reports of liver damage were assigned possible causality, and none were probable or certain causality. The clinical pharmacokinetic and animal toxicological information did not reveal unfavorable information about black cohosh. CONCLUSIONS Based on this safety review, the Dietary Supplement Information Expert Committee determined that black cohosh products should be labeled to include a cautionary statement. This is a change from the Expert Committee's decision of 2002, which required no such statement. With this decision, the US Pharmacopeia's Botanical Expert Committee may develop monographs for black cohosh, and the US Pharmacopeia may offer its verification programs to dietary supplement ingredient and product manufacturers.