Valdoxan (agomelatine) – Conditions or restrictions regarding supply and use - N06AX22

A.MANUFACTURERS RESPONSIBLE FOR BATCH RELEASE

Name and address of the manufacturers responsible for batch release

Les Laboratoires Servier Industrie, 905, route de Saran - 45520 Gidy, France Servier (Ireland) Industries Ltd, Gorey Road - Arklow - Co. Wicklow, Ireland

Przedsiebiorstwo Farmaceutyczne ANPHARM S.A., ul. Annopol 6B - 03-236 Warszawa, Poland Laboratorios Servier, S.L, Avda. de los Madroños, 33 -28043 Madrid, Spain

The printed package leaflet of the medicinal product must state the name and address of the manufacturer responsible for the release of the concerned batch.

B.CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE

Medicinal product subject to medical prescription.

C. OTHER CONDITIONS AND RE QUIREMENTS OF THE MARKETING AUTHORISATION

•Periodic Safety Update Reports

The requirements for submission of periodic safety update reports for this medicinal product areset out in the list of Union reference dates (EURD list) provided for under Article 107c(7) of Directive 2001/83/EC and any subsequent updates published on the European medicines web-portal.

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFEAND EFFECTIVE USE OF THE MEDICINAL PRODUCT

•Risk Management Plan (RMP)

The MAH shall perform the required pharmacovigilance activities and interventions detailed in the agreed RMP presented in Module 1.8.2 of the Marketing Authorisation andany agreed subsequent updates of the RMP.

An updated RMP should be submitted:

•Additional risk minimisation measures

The Marketing Authorisation Holder shall agree the format and contenof the physician’s guide to prescribing with the National Competent Authority prior to launch in the Member State.

The Marketing Authorisation Holder shall ensure that at launch and after launch all physicians who are expected to prescribe or use Valdoxan are provided with the updated educational material containing the following:

•The Summary of Product Characteristics;

•The Physician’s guide to prescribing, including a liver monitoring scheme.

The Physician’s guide to prescribing should contain the following key messages:

•The need to inform patients about the potential risk of transaminases elevations,the risk of liver injury and interactions with potent CYP 1A2 inhibitors (e.g. fluvoxamine, ciprofloxacin);

•The need to perform liver function tests in all patientsbefore starting treatment and periodically thereafter around three, six (end of acute phase), twelve and twenty four weeks (end of maintenance phase), and thereafter when clinically indicated;

•The need to perform liver function testsat the same frequency as at treatment initiation in all patients where the dosage is increased;

•Guidance in case of clinical symptoms of hepatic dysfunction;

•Guidance in case of liver function test abnormality;

•Caution should be exercised when therapy is administered to patients with pretreatment elevated transaminases (> the upper limit of the normal ranges and < 3 times the upper limit of the normal range);

substantial alcohol intake or concomitant medicinal products associated with risk of hepatic injury;

•Contra-indication in patients with hepatic impairment (i.e. cirrhosis or active liver disease);

•Contraindication in patients with transaminases exceeding 3 X upper limit of normal;

•Contra-indication in patients receiving concomitantly potent CYP1A2 inhibitors.

The Marketing Authorisation Holder shall agree the format and content of the patient booklet with the National Competent Authority in the Member State.

The Marketing Authorisation Holder shall ensure that all physicians who are expected to prescribe or use Valdoxan, are provided with patient booklets to be distributed to their patients being prescribed this medicine.

The Patient’s Booklet should contain the following key messages:

•Information about the risk of hepatic reactions and clinical signs of liver problems

•A guidance on the scheme of hepatic monitoring

•A blood tests appointments reminder.