Clinical study data on the safety of isopropanolic extract of Cimicifuga racemosa allow for its unlimited use according to ICH-E1

• Published in: Zeitschrift für Phytotherapie
• Main Authors: Henneicke-von Zepelin, HH, Garcia de Arriba, S, Nolte, KU
• Format: Conference Proceeding
• Language: English; German
• Published: 09.10.2015
• ISSN: 0722-348X; 1438-9584
• DOI: 10.1055/s-0035-1565967

The duration of use of medicinal products intended for non-life-threatening diseases is directly linked to a positive risk/benefit assessment based on clinical data over distinct exposure periods according ICH-E1 [1]. The HMPC monograph on Cimicifuga racemosa (CR) addressing ethanolic and isopropanolic extract of CR [2] states “Cimicifuga should not be taken for more than 6 months without medical advice”. Based on the ICH-E1-criteria, sufficient clinical study data are available to fulfill the ICH-E1-requirements for a safe long-term treatment – i.e. longer than 6 months – at least for the isopropanolic extract (iCR). We provide a reflection according to ICH-E1 on the product safety data from clinical studies on iCR, stratified if alone or in combination with a distinct ethanolic extract of Hypericum perforatum (eHP). According to ICH-E1, for a long-term treatment, the number of patients treated in clinical studies for 6 months at dosage levels intended for clinical use and monitored for Adverse Drug Reactions (ADR) must be at least 300 – 600 patients. This requirement is fulfilled by the 6,141 patients exposed to iCR (thereof 3,114 patients in combination with eHP) for at least 6 months in controlled non-interventional study [3] and several additional hundreds of patients in clinical studies on iCR alone (for a complete list see [4]). and the number of patients treated for 12 months from prospective studies and monitored for ADRs must be at least 100 patients. This requirement is fulfilled by the 736 patients exposed to iCR (thereof 399 patients in combination with eHP) for 12 months in a controlled non-interventional study [3]. the total number of individuals treated with the medicinal product, including short-term exposure, must be at least 1,500. This requirement is fulfilled by the total number of 11,961 patients exposed to iCR (thereof 4,176 patients in combination with eHP) in interventional and non-interventional clinical studies [3, 4, 5]. Due to this compliance, at least the iCR mentioned in the HMPC-monograph could be used for long-term treatment based on ICH-E1 (chronic or repeated intermitted use longer than 6 months). Independently from the sufficient extent of clinical data supporting the safe use of black cohosh, all menopausal women should seek routine medical advice every 6 to 12 months avoiding that relevant other diseases are overlooked. [1] EMEA. NfG: The Extent of Population Exposure to Assess Clinical Safety, CPMP/ICH/375/95 [2] EMA/HMPC/600717/2007 Corr.1, 2010 [3] Briese V. Maturitas 2007; 57: 405 – 414 [4] Beer AM. Evid Based Complement Alternat Med 2013; Art 860602 [5] Uebelhack R. Obstet Gynecol 2006; 107: 247 – 255