Meeting highlights from the CMDh meeting in December 2016
27.12.2016
CMDh positions on three joint PASS final study reports according to Art. 107q of Directive 2001/83/EC concerning cyproterone / ethinylestradiol
The CMDh, having considered the PRAC recommendations and the PRAC assessment reports for medicinal products containing cyproterone / ethinylestradiol concerned by the joint PASS final study reports, agreed by consensus that the below conditions imposed as a result of the Art. 107i referral on cyproterone / ethinylestradiol of the concerned marketing authorisations (i.e. those marketing authorisations for which the joint final study reports were submitted) may be removed by the MAH by a type IAIN variation under C.I.11.a:
"The MAH(s) should provide within the risk management plan submission, a protocol for the drug utilisation study to characterise prescribing practices for the medicinal products during typical clinical use in representative groups of prescribers and to assess main reasons for prescription. Final study report by 31 July 2015.
The MAH(s) should provide a protocol of a PASS within the risk management plan submission, to evaluate the effectiveness of the risk minimisation activities. Final study report by 31 July 2015.”
Consequently, where these imposed PASS are the only criteria for additional monitoring, MAHs should submit an additional type IAIN variation under C.I.12 to delete the black symbol and the related statement in the product information. This type IAIN variation can be grouped with the variation to delete the condition.
If there is a need to update the Risk Management Plan (marketing authorisation holders should consult the assessment report to be published under the below link), this needs to be done via the appropriate variation, which may be grouped with the above mentioned variations.
Further information regarding the above mentioned PSUSA procedures, including information on the implementation, will be published on the EMA website.
CMDh positions following PSUSA procedure for nationally authorised products only
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:
- captopril / hydrochlorothiazide
- ivermectin (topical use)
- thiopental
For the implementation of the PSUSA outcome for captopril / hydrochlorothiazide, the information in the section "Medicinal products containing ACE inhibitors” should also be consluted.
Further information regarding the above mentioned PSUSA procedures, including information on the implementation, will be published on the EMA website.
Outcomes of informal PSUR work-sharing procedures
The CMDh has adopted the conclusions of PSUR assessments for:
- chlorpromazine
- buprenorphine
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 worksharing 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.
Medicinal products containing ACE inhibitors
Following the finalisation of several PSUSAs, the CMDh was made aware that information from previously finalised procedure(s) by the originators is not reflected in the product information of all products (single active substance products and combinations).
For quinapril and quinapril / hydrochlorothiazide (HCT), this relates to the addition of warnings regarding increased risk of angioedema with ACE inhibitor use and concomitant mTOR inhibitor or concomitant DPP-IV inhibitor therapy, risk of severe hyperkalaemia with the coadministration of ACE inhibitors and trimethoprim-containing products as well as warnings regarding drug interactions such as concomitant use of ACE inhibitors and NSAIDs and an increased risk of reduced kidney function and concerning quinapril / HCT only concomitant use of thiazides with digoxin or gout medications.
For captopril / HCT, this relates to the outcome of the Renin-angiotensin-system (RAS)-acting agents Article 31 referral and the outcome of previously finalised procedure(s) CMDh/PhVWP/031/2011 related to use in pregnancy and lactation and of the worksharing PSUR FR/H/PSUR/005/002 related to the adverse events glaucoma and myopia.
In addition, the PRAC considered that the risk of angioedema in case of concomitant use with mTOR inhibitors and the risk of hyperkalaemia in case of concomitant use with co-trimoxazole as recommended for the combination captopril / HCT would also be relevant to be included in the product information of the captopril single agent as well as in that of all other ACE inhibitors, as it is a class effect.
In accordance with Article 23 Directive 2001/83/EC the marketing authorisation holder(s) are reminded of the obligation to keep the product information to date with the current scientific knowledge, including the conclusions of the assessment and recommendations made public by means of the European medicines web-portal.
The CMDh requests concerned MAHs to harmonise the product information on these aspects using variation worksharing procedures, where possible.
Implementation of HMPC public statement on contamination of herbal medicinal products with pyrrolizidine alkaloids
The Committee on Herbal Medicinal Products (HMPC) has recently published a public statement on contamination of herbal medicinal products/traditional herbal medicinal products with pyrrolizidine alkaloids (PAs) (EMA/HMPC/328782/2016). In the statement there are two main aspects relating to quality of herbal medicinal products (HMPs) that need to be addressed:
- Implementation of suitable testing procedures to ensure PA levels are controlled in line with limits agreed.
- Implementation of measures to avoid or reduce PA contamination in HMPs.
The CMDh advises MAHs for concerned MRP/DCP approved products to liaise with their RMS on appropriate regulatory action to be taken.
More news from the CMDh December 2016 meeting are available on the CMDh/HMA website.
