Risk management measures

The risk management system was introduced in European legislation in 2004, even though the Risk Management Plan (RMP) has been mandatory since 2012 with the entry into force of the new legislation which provided for mandatory submission of the RMP for each new marketing authorisation. Module V of the Guideline on good pharmacovigilance practices (GVP) is the reference guideline.

The objectives of the RMP according to the Commission Implementing Regulation (EU) n. 520/2012 are:

Identify the safety profile of the medicinal product concerned;
Indicate how to characterise further the safety profile of the medicinal product concerned;
Describe measures to prevent or minimise the risks associated with the medicinal product including an assessment of the effectiveness of those interventions
Document post-authorisation obligations that have been imposed as a condition of the marketing
authorisation (PASS, SEAP).

When should the RMP be submitted?

Upon each new Marketing Authorization (MA) in the context of the dossier of a new MA to AIFA’s MA Office
As a new introduction for a medicinal product already authorized in the context of a type II variation (C.I.11) and in other cases as identified by regulation (EC) no. 1234/2008, as amended, by using the front end system

An updated RMP shall be sent:

upon AIFA’s request
when the risk management system changes, especially if the changes arise from new information which can lead to major changes in the benefit/risk ratio

Educational materials

AIFA’s Risk Management Office is responsible for evaluating the Educational Material, if provided for by the Risk Management Plan (RMP). The evaluation procedure ends with an approval letter.

How to submit the application for evaluation:

The draft educational material shall be submitted to AIFA’s MGR Office. The authorization request of Educational materials shall be prepared in compliance with the "Guideline on good pharmacovigilance practices"(GVP) Module XVI and Module XVI Addendum I.

An electronic copy of the documentation to be approved shall be sent by e-mail to the following address: mgr@aifa.gov.it (please note that the files sent via e-mail cannot exceed 30MB). If deemed appropriate, the applicant could submit a hard copy. In this case, a digital copy (e-mail to mgr@aifa.gov.it or USB pendrive) should be provided anyway.

The documentation shall include the following *:

Cover letter
Distribution plan (which shall include a proposal for the target to be achieved as well as the methods and timing for its distribution)
Proposal of the educational material in an editable format in Italian, in order to allow revisions by the Risk Management Office
Copy of the last approved RMP

* For the list of necessary documents, please refer to GVP Form XVI and Form XVI Addendum I.

References

Module XVI – Risk minimisation measures: selection of tools and effectiveness indicators (Rev 2)

Module XVI Addendum I – Educational materials

Valproate and pregnancy

With an aim to improve awareness of the risks associated with the use of valproate in pregnancy, AIFA has agreed with the companies holders of valproate-based medicines the distribution of new educational materials for healthcare professionals and patients and the inclusion of a specific warning on the outer packaging of valproate-based medicinal products.

Upon the first prescription and throughout the duration of treatment, healthcare professionals and patients or carers can use such new educational materials to jointly discuss and evaluate the benefits and risks of using valproate in childbearing age and in relation to a possible pregnancy.

Please note that valproate should not be prescribed to girls, adolescents, women of childbearing age or pregnant women, unless strictly necessary, when other treatments have proven to be ineffective or have not been tolerated.

The new educational material consists of:

The HCP's Guide, the Patient Information Booklet, the Risk Acceptance Form and the Patient Reminder are tools designed to help HCPs manage and minimize the risks associated with the use of valproate in girls and in women of childbearing age or during pregnancy and to make sure that patients or their caregivers understand and accept the risks associated with such therapy.

You are reminded to provide the Patient Information Booklet and the Patient Reminder every time you prescribe (doctors) or distribute (pharmacists) a medicinal product containing valproate to a girl or woman of childbearing age or pregnant, unless the patient states that she already owns one.

It should also be noted that medicinal products containing valproate and related substances are marked with the ▼ symbol which identifies them as medicinal products subject to additional monitoring in order to allow the rapid identification of new safety information.

Further information and useful links:

Valproic acid - Medicines and pregnancy
Main references
Important information note on medicines containing valproate (08/08/2018)
Important information note on medicines containing va lproate (25/05/2016)
Valproate and pregnancy: updated data sheet on farmaciegravidanza.gov.it (18/03/2016)
Important information note on medicines containing valproate (05/02/2015)
Important information note on medicines containig valproate (05/12/2014)
CMDh strengthens recommendations on use of valproate (01/12/2014)
EMA communicaiton on valproate (21/11/2014)
New recommendations on use of valproate (20/10/2014);
PRAC recommendations on valproate (10/10/2014);
Valproate in pregnancy and congnitive delays in children: new evidence (06/10/2014);
PRAC recommendations on starting a re-evaluation of valproate and related substances (11/10/2013);
Epilepsy: medicines taken in pregnancy linked to developmental delays in children (09/09/2013)

Retinoid-based medicines

Retinoids (acitretin, adapalene, alitretinoin, bexarotene, isotretinoin, tazarotene and tretinoin) - update on teratogenicity and neuropsychiatric disorders

Medicines containing retinoids are available in oral and topical forms and are widely used to treat various forms of acne, severe chronic hand eczema unresponsive to corticosteroids, severe forms of psoriasis and keratinization disorders.

Tretinoin can also be used for the treatment of promyelocytic leukemia, and bexarotene is used in the treatment of the cutaneous manifestations of the advanced stage of cutaneous T-cell lymphoma.

Following a recent in-depth review of all relevant data, the European Pharmacovigilance Risk Assessment Committee (PRAC) has strengthened the warnings on teratogenicity and neuropsychiatric disorders reported with these medicines intended for patients and healthcare professionals (through information on the medicine and educational materials).

On this page you can find and download the Latest Approved Educational materials and the DHPC:

* INN (International NonProprietary Name): to be replaced with the name of the active ingredient

Educational material approved on 07/08/2018

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