Cmdh Press Release

13 December 2018 EMA/CMDh/708655/2018

Report from the CMDh meeting held on 10-12 December 2018

Brexit preparedness

The CMDh reminds MAHs that, in case of a no-deal Brexit, ongoing variations and renewals of procedures with UK as RMS, that are not finalised by 29 March 2019, will be stopped and will have to be resubmitted to the new RMS, once the RMS has been transferred to a RMS within the EU-27 (including EEA).

The CMDh agreed an update of the Practical guidance for procedures related to Brexit for medicinal products for human use approved via MRP/DCP. New Q&As on the change of a UK based applicant to a non-UK based applicant for an ongoing marketing authorisation application and on updates of ongoing MA applications with regards to other entities or activities currently located in the UK have been added.

The updated document will be published on the CMDh website under “Brexit”.

CMDh positions following PSUSA procedures 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:

 deoxycholic acid

 isotretinoin (oral formulations)

 ivermectin (topical use)

 nadroparin

 nortriptyline

 oxaliplatin

 oxycodone

 paracetamol (IV formulation)

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

Medicinal products containing paracetamol

During the assessment of the PSUSA on paracetamol (IV formulation), the PRAC noted that the sentence “Prospective data on pregnancies exposed to overdoses did not show an increase in malformation risk” is also included in the SmPC of other formulations/presentations of paracetamol medicinal products. The PRAC considered that the update of section 4.6 of the SmPC to delete a mention regarding pregnancies exposed to overdose of paracetamol is warranted for all paracetamol medicinal products (not restricted to the IV formulation), including products containing paracetamol in combination with other active substance(s).

Valid for all paracetamol containing medicinal products (including combination products)

Interaction between metamizole and acetylsalicylic acid (ASA)

During the assessment of the PSUSA on metamizole, the PRAC noted the following:

According to Section 4.5 of metamizole SmPCs: ‘Metamizole may reduce the effect of acetylsalicylic acid (aspirin) on platelet aggregation, when taken concomitantly. Therefore, this combination should be used with caution in patients taking low dose aspirin for cardioprotection.’ This interaction is not included in the SmPCs of low-dose ASA indicated for secondary cardiovascular prevention. Similar pharmacodynamic interaction resulting in the inhibition of platelet activity has been proposed for certain NSAIDs, including ibuprofen and naproxen. Contrary to the information on the potential interaction with metamizole, reduction of antiplatelet effect of low-dose ASA when co-administered with naproxen or ibuprofen, is flagged in the SmPC of low-dose ASA (originator). For consistency reasons, the pharmacodynamic interaction of ASA and metamizole resulting in high on-treatment platelet reactivity in patients should also be included in the product information of low-dose ASA products indicated for the secondary prevention of cardiovascular events.

Valid for medicinal products containing low-dose acetylsalicylic acid indicated for secondary cardiovascular prevention

Medicinal products containing efavirenz in combination

During the assessment of the PSUSA on efavirenz, the PRAC noted that efavirenz is also authorised in fixed dose combination products with emtricitabine/tenofovir disoproxil. The PRAC considers that information related to the drug-drug interaction with etonogestrel implant are also relevant for the fixed-dose combinations of efavirenz. Therefore, the PRAC recommends that the MAHs should implement the respective updates also for these products.