• 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

Additional Risk minimisation measures (aRMM) are targeted interventions that complement routine risk minimisation measures (Summary of product characteristics, Package leaflet, labelling of immediate and outer packaging, Pack size, legal status) and are intended to prevent or mitigate specific risks identified in the safety profile of a medicinal product and to promote its safe and effective use.

aRMM may include Educational/Safety advice tools intended for healthcare professionals and patients (e.g. Patient card, Guides for risk minimisation for patients and healthcare professionals, Patient diary for risk minimisation), as well as Risk minimisation control tools, such as controlled access or controlled distribution programmes.

The Risk Management Office (UMGR) within AIFA’s Post Marketing Surveillance Division (AVPM) is the office responsible for the assessment and approval of aRMM, where these are required under the Risk management plan (RMP) as a condition for the marketing authorisation of the medicinal product. The assessment procedure is concluded by the issuance of an approval decision.

Where the medicinal product authorisation provides for the Patient card included in the package as the sole aRMM, and such Patient Card has already been approved through the relevant authorisation procedure, the Marketing authorisation holder (MAH) shall nevertheless submit an application to the UMGR requesting approval of a Healthcare professional communication regarding the Patient card and of the corresponding Distribution plan.
 

How to submit an assessment application

The documentation shall be submitted to the Risk Management Office (UMGR) by Certified Electronic Mail (PEC) to the following address: protocollo@pec.aifa.gov.it. At the beginning of the subject line, the application must include the acronym “MGR” in order to facilitate routing to the competent Office. In addition, a copy of the application shall also be sent to: mgr@aifa.gov.it.

Please note that files transmitted by e-mail must not exceed 30 MB. Larger files (e.g. videos) may be submitted via Eudralink.

The application for approval of the aRMM shall be prepared in accordance with the provisions of Module XVI of the Guideline on Good Pharmacovigilance Practices (Rev. 3, 2024).
The application for the implementation or update of aRMM shall be submitted upon completion of the regulatory procedure introducing or updating the relevant measure.
Please note that, for newly authorised medicinal products, where aRMM are required as a condition of the Marketing authorisation (MA), the Marketing authorisation holder (MAH) is obliged to distribute the Educational/Safety advice tools or any other aRMM to the target population before the medicinal product is placed on the national market. The application shall be submitted at least 60 days before the planned date of commencement of marketing of the medicinal product.

For medicinal products granted a new marketing authorisation through the centralised procedure, the application for approval of the aRMM, where required by the RMP, shall be submitted to the UMGR as part of the national implementation phase.

List of documents to be submitted:

For all medicinal products

• Application for assessment of aRMM (Cover Letter)
• Outcome of the regulatory procedure providing for the implementation/update of the aRMM:
  • For medicinal products authorised through National Procedure (NP), Mutual Recognition Procedure (MRP) or Decentralised Procedure (DCP): Marketing Authorisation (MA) Decision;
  • For medicinal products authorised through the Centralised Procedure (CP): EMA CHMP Opinion and/or European Commission Decision.
• RMP (latest approved version)
• Product information texts (common texts)
• Proposal of the Italian-language “text-only” version of the documents envisaged as Educational/Safety advice tools (editable Word format)
• Proposal for a Healthcare Professional Communication on the additional Risk Minimisation Measures (aRMM)
• Proposal for a Distribution Plan, including the recipients (distribution target) of the Educational/Safety advice tools, as well as the methods and timelines for their distribution.

For medicinal products authorised through any procedure for which the Patient Card, as an integral part of the Product Information and included in the package, constitutes the sole aRMM

• Patient card already approved through the relevant authorisation procedure
• Proposal for a Healthcare Professional Communication regarding the Patient card and for the corresponding Distribution Plan for such Communication.

A consortium of companies may be established for the purpose of submitting a coordinated application. In such cases, a lead company shall be designated to act as the contact point with the UMGR.

It should also be noted that, where aRMM are required under the Risk management plan (RMP) as a condition for the marketing authorisation of the medicinal product, in the event of a transfer of the Marketing Authorisation, the acquiring company shall submit an application to the UMGR requesting assessment for the re-approval and subsequent distribution of the materials updated with the details of the new Marketing Authorisation Holder.

Regulatory References:

• Italian Ministry of Health Decree of 30 April 2015
• Regulation (EU) No 1235/2010
• Commission Implementing Regulation (EU) No 520/2012
• Guideline on Good Pharmacovigilance Practices (GVP) Module XVI – Risk Minimisation Measures (Rev. 3)
• Guideline on Good Pharmacovigilance Practices (GVP) Module XVI Addendum I – Risk Minimisation Measures for Medicinal Products with Embryo-Fetal Risks
• Guideline on Good Pharmacovigilance Practices (GVP) Module XVI Addendum II – Methods for Evaluating the Effectiveness of Risk Minimisation Measures
• Guideline on Good Pharmacovigilance Practices (GVP) Module V – Risk Management Systems (Rev. 2)
• Guidance on the Format of the Risk Management Plan (RMP) in the EU – Integrated Format

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:

• Guide for Healthcare professionals
• Guide for Patients
• Annual Risk Acceptance Form
• Patient reminder

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 valproate (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)

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:

• Checklist for the pharmacist *
• Material for doctors *
• Material for patients - reminder card *

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

Educational material approved on 17/05/2024

Lenalidomide is approved as monotherapy or in combination in several therapeutic indications. For a complete list of the approved indications for each lenalidomide-based medicinal product, posology and method of administration, please refer to the Summary of Product Characteristics (SmPC) of the corresponding medicinal product and/or the cover letter published below.

In particular, due to the potential risk of embryo-fetal toxicity, the use of lenalidomide-based medicinal products is contraindicated during pregnancy. It is also contraindicated in women of childbearing potential unless all conditions are met of the Pregnancy Prevention Program (PPP) developed for lenalidomide.

If lenalidomide is taken during pregnancy, a teratogenic effect is expected.

The PPP is an integral part of the risk minimisation plan, which also includes educational materials for healthcare professionals, patient educational brochures and a patient sheet. Its goal is to reduce and prevent the risks associated with the use of lenalidomide.

As required by the PPP, all Healthcare professionals involved must have read and understood the Educational Material before prescribing or dispensing lenalidomide to any patient.

Lenalidomide must be prescribed and dispensed through the AIFA Multi-Drug Monitoring Registry for drugs under the pregnancy prevention program (PPP).

On this page you can download the Latest Approved Educational materials.

1. Cover letters with indications and dosage
2. Handbook for Healthcare Professionals
3. Checklist for the Pregnancy Prevention Program (PPP)
4. Patient Handbook
5. Patient sheet
6. Adverse Event Reporting Form
7. Pregnancy Reporting Form