Use of herbal medicinal products containing toxic, unsaturated pyrrolizidine alkaloids (PAs) - Scientific guideline

This guidance describes chemical, toxicological, pharmacological and pharmacokinetic properties of unsaturated pyrrolizidine alkaloids (PAs). It sets out recommendations for the oral and cutaneous use of herbal medicinal products and traditional herbal medicinal products containing PAs.

Keywords: Herbal medicinal products, pyrrolizidine alkaloids

Current version

Public statement on the use of herbal medicinal products containing toxic, unsaturated pyrrolizidine alkaloids (PAs) including recommendations regarding contamination of herbal medicinal products with pyrrolizidine alkaloids - Revision 1

AdoptedReference Number: EMA/HMPC/893108/2011 Rev. 1

Document history

Overview of comments received on draft revised Public statement on the use of herbal medicinal products containing toxic, unsaturated pyrrolizidine alkaloids (PAs) (EMA/HMPC/893108/2011 Rev. 1)

Reference Number: EMA/HMPC/3914/2021

Draft public statement on the use of herbal medicinal products containing toxic, unsaturated pyrrolizidine alkaloids (PAs) including recommendations regarding contamination of herbal medicinal products with pyrrolizidine alkaloids - Revision 1

Consultation dates: 15/08/2020 to 15/11/2020Draft: consultation closedReference Number: EMA/HMPC/893108/2011 Rev. 1Summary:

The completed comments form should be sent to [e-mail]

Call for scientific data for use in HMPC assessment work on ‘Public statement on the use of herbal medicinal products containing toxic, unsaturated pyrrolizidine alkaloids (PAs) - First version’

Consultation dates: 28/02/2019 to 31/08/2019Draft: consultation closedReference Number: EMA/HMPC/39600/2019

Public statement on the use of herbal medicinal products containing toxic, unsaturated pyrrolizidine alkaloids (PAs) - First version

AdoptedReference Number: EMA/HMPC/893108/2011Summary:

It became apparent during assessment of Symphytum officinale (monograph EMEA/HMPC/572844/2009) that the risk assessment of pyrrolizidine alkaloids (PAs) poses considerable difficulties, with several PAs being regarded as both hepatotoxic and carcinogenic.

Overview of comments received on the second draft Public statement on the use of herbal medicinal products containing toxic unsaturated pyrrolizidine alkaloids (PAs)

Consultation dates: 22/12/2014 to 31/03/2015Reference Number: EMA/HMPC/577756/2014

Second draft public statement on the use of herbal medicinal products containing toxic, unsaturated pyrrolizidine alkaloids (PAs)

Consultation dates: 14/11/2013 to 15/02/2014Draft: consultation closedReference Number: EMA/HMPC/893108/2011 2nd draftSummary:

It became apparent during assessment of Symphytum officinale (monograph EMEA/HMPC/572844/2009) that the risk assessment of pyrrolizidine alkaloids (PAs) poses considerable difficulties, with several PAs being regarded as both hepatotoxic and carcinogenic. Considering that PAs are natural constituents of a number of plants used for medicinal purposes and that PAs might be part of the food chain, the HMPC decided to prepare a public statement on the use of herbal preparations containing PAs.

Overview of comments received on the draft Public statement on the use of herbal medicinal products containing toxic unsaturated pyrrolizidine alkaloids (PAs)

Reference Number: EMEA/HMPC/411398/2006

Draft public statement on the use of herbal medicinal products containing toxic, unsaturated pyrrolizidine alkaloids

Consultation dates: 25/10/2012 to 15/02/2013Draft: consultation closedReference Number: EMA/HMPC/893108/2011Summary:

It became apparent during assessment of Symphytum officinale (monograph EMEA/HMPC/572844/2009) that the risk assessment of pyrrolizidine alkaloids (PAs) poses considerable difficulties, with several PAs being regarded as both hepatotoxic and carcinogenic. Considering that PAs are natural constituents of a number of plants used for medicinal purposes and that PAs might be part of the food chain, the Committee on Herbal Medicinal Products decided to prepare a public statement on the use of herbal preparations containing PAs.