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Salvia Miltiorrhiza Bunge, Radix Et Rhizoma Draft 13 January 2021 EMA/HMPC/509932/2019 Committee on Herbal Medicinal Products (HMPC) Assessment report on Salvia miltiorrhiza Bunge, radix et rhizoma Draft Based on Article 10a of Directive 2001/83/EC as amended (well-established use) Based on Article 16d(1), Article 16f and Article 16h of Directive 2001/83/EC as amended (traditional use) Herbal substance(s) (binomial scientific name of the plant, including plant part) Salviae miltiorrhizae Bunge, radix et rhizoma Herbal preparation(s) Not applicable Pharmaceutical form(s) Not applicable Rapporteur(s) J. Wiesner Assessor(s) M. Peikert Peer-reviewer B. Kroes Note: This draft assessment report is published to support the public consultation of the draft public statement on Salvia miltiorrhiza Bunge, radix et rhizoma. It is a working document, not yet edited, and shall be further developed after the release for consultation of the public statement. Interested parties are welcome to submit comments to the HMPC secretariat, which will be taken into consideration but no ‘overview of comments received during the public consultation’ will be prepared on comments that will be received on this assessment report. The publication of this draft assessment report has been agreed to facilitate the understanding by Interested Parties of the assessment that has been carried out so far and led to the preparation of the draft public statement. Official address Domenico Scarlattilaan 6 ● 1083 HS Amsterdam ● The Netherlands Address for visits and deliveries Refer to www.ema.europa.eu/how-to-find-us An agency of the European Union Send us a question Go to www.ema.europa.eu/contact Telephone +31 (0)88 781 6000 © European Medicines Agency, 2021. Reproduction is authorised provided the source is acknowledged. Table of contents Introduction .......................................................................................................................... 4 1.1. Description of the herbal substance(s), herbal preparation(s) or combinations thereof .. 4 1.2. Search and assessment methodology ..................................................................... 7 2. Data on medicinal use ........................................................................................................ 7 2.1. Information about products on the market .............................................................. 7 2.1.1. Information about products on the market in the EU/EEA Member States ................. 7 2.1.2. Information on products on the market outside the EU/EEA .................................... 8 2.2. Information on documented medicinal use and historical data from literature .............. 9 2.3. Overall conclusions on medicinal use .................................................................... 14 ...................................................................................................... Error! Bookmark not defined. 3. Non-Clinical Data ............................................................................................................. 15 3.1. Overview of available pharmacological data regarding the herbal substance(s), herbal preparation(s) and relevant constituents thereof ........................................................... 15 3.1.1. Primary pharmacodynamics .............................................................................. 15 3.1.2. Secondary pharmacodynamics .......................................................................... 20 3.1.3. Safety pharmacology ....................................................................................... 20 3.1.4. Pharmacodynamic interactions .......................................................................... 21 3.1.5. Conclusions .................................................................................................... 23 3.2. Overview of available pharmacokinetic data regarding the herbal substance(s), herbal preparation(s) and relevant constituents thereof ........................................................... 23 3.3. Overview of available toxicological data regarding the herbal substance(s)/herbal preparation(s) and constituents thereof ....................................................................... 27 3.3.1. Single dose toxicity .......................................................................................... 27 3.3.2. Repeat dose toxicity ......................................................................................... 27 3.3.3. Genotoxicity ................................................................................................... 28 3.3.4. Carcinogenicity ................................................................................................ 28 3.3.5. Reproductive and developmental toxicity ............................................................ 28 3.3.6. Local tolerance ................................................................................................ 28 3.3.7. Other special studies ........................................................................................ 28 3.3.8. Conclusions .................................................................................................... 29 3.4. Overall conclusions on non-clinical data ................................................................ 29 4. Clinical Data ..................................................................................................................... 29 4.1. Clinical pharmacology ......................................................................................... 29 4.1.1. Overview of pharmacodynamic data regarding the herbal substance(s)/preparation(s) including data on relevant constituents ........................................................................ 29 4.1.2. Overview of pharmacokinetic data regarding the herbal substance(s)/preparation(s) including data on relevant constituents ........................................................................ 30 4.2. Clinical efficacy .................................................................................................. 30 4.2.1. Dose response studies...................................................................................... 30 Assessment report on Salvia miltiorrhiza Bunge, radix et rhizoma EMA/HMPC/509932/2019 Page 2/41 4.2.2. Clinical studies (case studies and clinical trials) ................................................... 30 4.3. Clinical studies in special populations (e.g. elderly and children) .............................. 36 4.4. Overall conclusions on clinical pharmacology and efficacy ........................................ 36 4.5. Overview of toxicological/safety data from clinical trials in humans ........................... 36 4.6. Patient exposure ................................................................................................ 36 4.7. Adverse events, serious adverse events and deaths ................................................ 37 4.8. Laboratory findings ............................................................................................. 38 4.9. Safety in special populations and situations ........................................................... 38 4.9.1. Use in children and adolescents ......................................................................... 38 4.9.2. Contraindications ............................................................................................. 38 4.9.3. Drug interactions and other forms of interaction .................................................. 38 4.9.4. Fertility, pregnancy and lactation ....................................................................... 39 4.9.5. Overdose ........................................................................................................ 40 4.9.6. Effects on ability to drive or operate machinery or impairment of mental ability ...... 40 4.9.7. Safety in other special situations ....................................................................... 40 4.10. Overall conclusions on clinical safety ................................................................... 40 5. Overall conclusions (benefit-risk assessment) ................................................................. 41 Annex .................................................................................................................................. 41 List of references ...................................................................................................... 41 Assessment report on Salvia miltiorrhiza Bunge, radix et rhizoma EMA/HMPC/509932/2019 Page 3/41 1. Introduction 1.1. Description of the herbal substance(s), herbal preparation(s) or combinations thereof In international pharmacopoeias different herbal substances and herbal preparations from Salvia miltiorrhiza are monographed • Herbal substance(s) “Danshen” consist of the dried, whole or fragmented rhizome and root (Ph. Eur. 2017; ChPh 2015) European Pharmacopoeia (2013, 2017) Salvia miltiorrhiza root is covered by the 8th edition of the European Pharmacopoeia (2013). Salvia miltiorrhiza root and rhizome consist of the dried, whole or fragmented rhizome and root of Salvia miltiorrhiza Bunge collected in spring or autumn, containing minimum 3.0 percent of salvianolic acid B (C36H30O16; Mr 719) and minimum 0.12 percent of tanshinone II (C19H18O3; Mr 294.3). Chinese Pharmacopoeia (1963, 1977, 1985, 1990, 1995, 2000, 2005, 2010 and 2015) The Chinese Pharmacopoeia: “Danshen”: the dried whole or fragmented rhizome and root. • Herbal preparation(s) "Processed" /baked with
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