CMDh News – November 2015


CMDh outcome on referrals pursuant to Article 31 of Directive 2001/83/EC

Ambroxol and bromhexine-containing medicines

The Co-ordination Group for Mutual Recognition Procedure and Decentralised Procedures for Human Medicinal Products (CMDh), having considered the revised PRAC assessment report and recommendation, agreed by majority that the marketing authorisations for ambroxol and bromhexine-containing medicines should be updated with information about the small risk of severe allergic reactions and severe cutaneous adverse reactions (SCARs). The CMDh position has been forwarded to the European Commission who will take the final decision. Upon receipt of the Commission Decision, marketing authorisation holders should implement the outcome via type IB variation, in accordance with the CMDh Q&A on variation No. 3.20 (

Additional information is available at EMA's website:

The CMDh emphasises that all the available data submitted was assessed with regard to the potential impact of the new safety concerns identified on the established benefit-risk balance of the authorised medicinal products. Therefore, the unchanged positive benefit-risk balance in the revised PRAC recommendation refers to the existing marketing authorisations that were subject to the review. Further amendments beyond those agreed as part of the referral outcome would require the submission of the appropriate data and would be subject to assessment at national level by the relevant competent authorities.

CMDh positions following PSUSA procedure for only nationally authorised products

The CMDh, having considered the PSURs on the basis of the PRAC recommendations and the PRAC assessment reports, agreed by consensus on the variations of the marketing authorisations of medicinal products containing the following active substances:

  • Spironolactone
  • Trandolapril/verapamil

Further information on the implementation of a corresponding wording for the warning on the interaction between dabigatran and verapamil in medicinal products containing verapamil as monocomponent or verapamil in other combinations will be made available by the CMDh in due time.

Further information regarding the above-mentioned PSUSA procedures, including information on the implementation, will be published on the EMA website, or here.

Outcomes of informal PSUR work-sharing procedures

The CMDh has adopted the conclusions of PSUR assessments for:

  • benazepril/hydrochlorothiazide
  • ciprofloxacin hydrochloride/dexamethasone acetate (ear drops, suspension)
  • human coagulation factor VIII inhibitor bypassing fraction
  • ivermectin
  • pravastatin
  • tiapride

which may require changes to the product information or introduction of other risk minimisation measures.

The public summaries will be published on the CMDh website under "Pharmacovigilance, PSURs, Outcome of informal PSUR work-sharing procedures”.

MAHs of the products concerned should implement the outcome of the assessment by the appropriate variation or other procedure (as advised) within 90 days of publication.

Safety related variations

The CMDh once again would like to stress the importance of submitting safety related variations (e.g. new contraindications, new side effects and interactions) for purely national marketing authorisations via a work-sharing procedure.

List of safety concerns per approved Risk Management Plan (RMP) of active substances per product

The CMDh has agreed a revision of the cover note to the list of safety concerns per approved Risk Management Plan (RMP) of active substances per product to clarify when MAHs should provide additional safety concerns of new approved RMPs. The updated cover note will be published under "Pharmacovigilance, RMP”.

One month to go until the mandatory use of the electronic application form

The CMDh would like to remind about the mandatory use of electronic application form (eAF) for granting marketing authorisations, renewals and variations for medicinal products within national and MRP/DCP procedures, which will begin soon. The use of these application forms for centralised procedure has been mandatory since 1st July 2015, whereas for national and MRP/DCP procedures it will become mandatory from 1st January 2016.

News from the CMDh November meeting are available on the CMDh/HMA webpages, or here.