• 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

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

How to submit the application for evaluation:
The draft educational material shall be submitted to AIFA’s Risk Management Office by certified email (PEC) at the following address: protocollo@pec.aifa.gov.it.

In order to correctly sort and direct the application, the e-mail subject line must start with the acronym “MGR”.
Furthermore, a copy of the application must be submitted  to the e-mail address: mgr@aifa.gov.it, as well.

The documents sent by e-mail should not exceed 30Mb. When the files size exceed  this limit, the submission could be performed by Eudralink. The application for authorisation of the Educational materials shall be prepared in compliance with the "Guideline on good pharmacovigilance practices” (GVP) Module XVI. For new MAs, the application must be submitted at least 60 days before the expected marketing date of the medicinal product. In the case of already marketed medicinal products, the application for insertion or updating of the Educational Material shall take place at the end of the regulatory procedure implementing the aforementioned measure.

Exclusively for new MAs of medicines authorised with centralised procedure, the application for approval of the Educational Material, if required by the RMP, must be filed with the MGR Office as part of the national phase.

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 for revisions by the Risk Management Office.
• Copy of the last RMP approved.
• Any common texts, specifying whether they are approved by the EMA or by other Authority.
• MA resolution for the products approved through national, mutual recognition and decentralised procedures.
• Outcome of the regulatory procedure whereby it was decided to implement/update the Educational Material.

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

Please note that before the medicinal product is marketed on the national territory, the marketing authorisation holder is required to distribute the educational material or other risk minimisation measure if provided for by the RMP.

References:
Guideline on good pharmacovigilance practices (GVP) "Module XVI – Risk minimisation measures (Rev 3)"

Direct Healthcare Professional Communications (DHPCs) constitute a key instrument for disseminating critical safety information regarding medicinal products to healthcare professionals.

The Pharmacovigilance Office (FV) of the Italian Medicines Agency (AIFA) is responsible for the assessment and authorization of DHPCs, referred to in Italian as Note Informative Importanti di Sicurezza (NIIS).

DHPCs may be initiated:

• at the request of the competent regulatory authorities,
• or upon proposal by the Marketing Authorization Holder (MAH).

In all circumstances, the content of the DHPC must be agreed upon with the competent authority.

Submission of Evaluation Requests
Requests must be submitted exclusively via Certified Electronic Mail (PEC) to the following address: protocollo@pec.aifa.gov.it.

The submission must comply with the timelines established in the Communication and Distribution Plan (PCD), as defined by the competent authority following the conclusion of a safety evaluation procedure.

For DHPCs proposed on the initiative of the MAH, the request must be submitted at least 60 days prior to the intended distribution date, except in cases of duly justified urgency.

Required Documentation
The request must be accompanied by the following documentation:

1. Cover letter from the MAH outlining the rationale for the DHPC. If available, the communication received from the competent authority should also be attached.
2. Email address of the designated company contact for correspondence with the Pharmacovigilance Office.
3. Draft DHPC in both Italian and English, provided in editable format (e.g., Microsoft Word).
4. Proposed Communication and Distribution Plan (PCD), which must include: 
   • Start and end dates of the distribution period;
   • Format and method of distribution (e.g., electronic mail and/or hard copy);
   • Type and number of recipients.

Coordination of DHPCs Involving Multiple Companies
In cases where a DHPC concerns multiple MAHs, a lead company shall be designated to act as the unique contact point. The lead company is responsible for:

• Liaising with the Pharmacovigilance Office to define the content, translation, and PCD of the DHPC;
• Coordinating the involved companies and ensuring the joint submission of the communication.

From the moment the lead company is appointed, all communications and interactions shall be conducted exclusively between the Pharmacovigilance Office and the designated lead company.

Approval and Distribution
Once the Italian version of the DHPC and the PCD have been finalized and agreed upon, the Pharmacovigilance Office will issue formal approval via an official letter addressed to all involved companies.
 

References:

• Guideline on good pharmacovigilance practices (GVP) Module XV - Safety communication (Rev 1)
• Module XV Annex II:      
  • Direct Healthcare Professional Communication 
  • Communication Plan for Direct Healthcare Professional Communication

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