Whether Metal Element-Containing Herbal Formula Angong Niuhuang Pill Is Safe for Acute Brain Disorders?

"Angong Niuhuang Pill" (AGNH Pill) has been used as patented herbal formula for treatment of acute brain disorders including ischemic stroke, hemorrhage stroke, and trauma brain injury in traditional Chinese medicine for a thousand years. It is widely used in treatment of many diseases. As AGNH Pill contains metal elements named realgar and cinnabar, whether AGNH Pill is safe attracts great concerns. To address this question, we reviewed adverse drug reactions (ADR) and adverse events (AE) to assess the safety of AGNH Pill clinically. We searched PubMed, Embase, Cochrane library, TOXNET, and Chinese databases CNKI and Wanfang for articles published between January 1974 and January 2015. A total of 49 cases contained in 10 articles were included in this study. We were unable to determine the frequency of ADR/AE induced by AGNH Pill due to the lack of complete production and market information provided by pharmaceutical manufacturers and hospitals. Based on current literature data, we estimated that the risk of ADR/AE from AGNH Pill administration was low. The majority of ADR/AE was attributed to the improper use of AGNH Pill, such as use in children with overdosage or use with incompatible drugs. We were unable to distinguish whether incidents were ADR or AE because of the poor reports. To date, published evidence indicates that AGNH Pill appears to carry a relatively low risk of ADR/AE. As the quality of clinical assessment for the safety of AGNH Pill is poor, it is desirable to conduct well-designed randomized clinical trials to assess its safety for the treatment of acute brain disorders.