Patient Information Leaflet: Package Leaflet

Valdoxan 25 mg Film-Coated Tablets

agomelatine

Read this leaflet carefully before you start taking this medicine because it contains important information for you.

• Keep this leaflet, as you may need to read it again.

• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others even if they have similar symptoms, as it may harm them.
• If you experience any side effects, talk to your doctor or pharmacist. See section 4.

Valdoxan contains the active ingredient agomelatine. Agomelatine belongs to a group of medicines called antidepressants. Valdoxan has been prescribed for you to treat your depression. Valdoxan is used in adults.

Depression is a continued alteration of mood that interferes with daily life. The symptoms of depression vary from person to person, but usually consist of a deep sadness, feelings of uselessness, loss of interest in hobbies, sleep disturbances, feeling of slowness, feeling of anxiety, and weight changes.

The expected benefits of Valdoxan are to gradually reduce and eliminate the symptoms related to your depression.

Do not take Valdoxan

• If you are allergic to agomelatine or any of the other components of this medication (listed in section 6).

• If your liver does not function properly (liver insufficiency).
• If you are taking fluvoxamine (another medication used to treat depression) or ciprofloxacin (an antibiotic).

Warnings and precautions

There may be reasons why Valdoxan is not suitable for you:

• If you are taking medications that are known to affect the liver. Ask your doctor for advice on these medications.
• If you have obesity or overweight, ask your doctor for advice.

• If you are diabetic, ask your doctor for advice.
• If you have elevated liver enzyme levels before treatment, your doctor will decide if Valdoxan is appropriate for you.
• If you have bipolar disorder, have experienced or develop manic symptoms (a period of excessive excitement and abnormal emotional elevation), inform your doctor before starting to take this medication or before continuing to take it (see also “Possible side effects” in section 4).

• If you have dementia, your doctor will perform an individual assessment to decide if it is appropriate for you to take Valdoxan.

During your treatment with Valdoxan:

What to do to avoid potentially serious liver problems:

• Your doctor must check that your liver is functioning correctlybefore starting treatment.Some patients may experience increases in blood levels of liver enzymes during treatment with Valdoxan. Therefore, follow-up analyses should be performed with the following frequency:

Based on the evaluation of these analyses, your doctor will decide if you should receive or continue to use Valdoxan (see also section 3 “How to take Valdoxan”).

Be aware of the signs and symptoms that may indicate that your liver is not functioning properly.

• If you notice any of these signs and symptoms of liver problems:unusual darkening of urine, pale stools, yellowing of the skin/eyes, upper right abdominal pain, unusual fatigue (especially associated with other previously mentioned symptoms), seek urgent advice from a doctor, who may recommend discontinuing treatment with Valdoxan.

The effect of Valdoxan has not been documented in patients over 75 years. Valdoxan should therefore not be used in these patients.

Thoughts of suicide and worsening of depression

If you are depressed, you may occasionally have thoughts of self-harm or suicide. These thoughts may be increased at the beginning of treatment with antidepressants, as all these medications take time to exert their effect, usually two weeks but sometimes longer.

You are more likely to have these thoughts:

• If you have previously had thoughts of self-harm or suicide.
• If you are a young adult. There is information from clinical trials that has shown an increased risk of suicidal behavior in young adults (under 25 years) who have a psychiatric disorder and are being treated with antidepressants.

Contact your doctor or go directly to the hospital as soon as you have any thoughts of self-harm or suicide.

It may be helpful to tell a close relative or friend that you are depressed and ask them to read this leaflet. You can ask them to tell you if they notice that your depression is worsening, or if they are concerned about changes in your behavior.

Children and adolescents

Valdoxan is not recommended for children under 7 years due to lack of information. There are no available data.

Valdoxan should not be used in children and adolescents from 7 to 17 years because its safety and efficacy have not been established.

Other medications and Valdoxan

Inform your doctor or pharmacist if you are using or have recently used or may need to take any other medication.

You should not take Valdoxan with certain medications (see also “Do not take Valdoxan” in section 2): fluvoxamine (another medication used to treat depression) and ciprofloxacin (an antibiotic) as they may modify the planned dose of agomelatine in your blood.

Make sure to inform your doctor if you are taking any of the following medications: propranolol (a beta-blocker used to treat hypertension), enoxacine (an antibiotic).

Make sure to inform your doctor if you smoke more than 15 cigarettes per day.

Valdoxan and alcohol

It is not recommended to drink alcohol while being treated with Valdoxan.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, or think you may be pregnant, consult your doctor or pharmacist before using this medication.

Breastfeeding should be discontinued if you take Valdoxan.

Driving and operating machinery

You may feel dizziness or drowsiness that may affect your ability to drive or operate machinery. Make sure your reaction is normal before driving or operating machinery.

Valdoxan contains lactose

If your doctor has told you that you have a certain sugar intolerance, consult with him before taking this medication.

Valdoxan contains sodium

Valdoxan contains less than 1 mmol of sodium (23 mg) per tablet; it is essentially “sodium-free”.

Follow exactly the administration instructions of this medication indicated by your doctor or pharmacist. In case of doubt, consult your doctor or pharmacist again.

The recommended dose of Valdoxan is one tablet (25 mg) before bedtime. In some cases, your doctor may prescribe a higher dose (50 mg), that is, two tablets that must be taken together before bedtime.

Administration Method

Valdoxan is for oral administration. You should swallow your tablet with the help of a glass of water.

You can take Valdoxan with or without food.

Treatment Duration

In most people with depression, Valdoxan starts to act on depression symptoms within two weeks of starting treatment.

Your depression should be treated for a sufficient period of at least 6 months to ensure that you no longer have symptoms.

Your doctor may continue prescribing Valdoxan when you feel better to prevent depression from coming back.

If you have kidney problems, your doctor will perform an individual evaluation to decide if it is safe for you to take Valdoxan.

Liver function monitoring (see also section 2):

Your doctor will ask for tests to check that your liver is functioning properly before starting treatment and, afterwards, periodically during treatment, usually after 3 weeks, 6 weeks, 12 weeks, and 24 weeks. If your doctor increases the dose to 50 mg, tests should be performed at the time of dose increase and, afterwards, periodically during treatment, usually after 3 weeks, 6 weeks, 12 weeks, and 24 weeks. Afterwards, tests will be performed if the doctor considers it necessary.

You should not use Valdoxan if your liver is not functioning properly.

How to switch from an antidepressant (SSRI / SNRI) to Valdoxan?

If your doctor changes your previous antidepressant medication from an SSRI or SNRI to Valdoxan, they will inform you about how to stop treatment with your previous medication when you start taking Valdoxan.

You may experience withdrawal symptoms related to the interruption of previous treatment for several weeks, even if the dose of your previous antidepressant medication is gradually reduced.

Withdrawal symptoms include: dizziness, numbness, sleep disturbance, agitation or anxiety, headache, nausea, vomiting, and tremors. These effects are generally mild to moderate and disappear spontaneously within a few days.

If treatment with Valdoxan starts while the dose of the previous medication is gradually reduced, possible withdrawal symptoms should not be confused with a lack of effect of Valdoxan at the beginning of treatment.

You should consult your doctor about the best way to interrupt your previous antidepressant treatment when starting treatment with Valdoxan.

If you take more Valdoxan than you should

If you have taken more Valdoxan tablets than you should, or if, for example, a child has taken the medication by accident, contact your doctor immediately.

The experience of overdose with Valdoxan is limited, but reported symptoms include upper stomach pain, drowsiness, fatigue, agitation, anxiety, tension, dizziness, cyanosis, or general discomfort.

If you forget to take Valdoxan

Do not take a double dose to compensate for the missed doses. Simply take the next dose at the usual time.

The printed calendar in the blister pack containing the tablets will help you remember when you last took a Valdoxan tablet.

If you interrupt treatment with Valdoxan

Do not stop taking your medication without consulting your doctor, even if you feel better.

If you have any other questions about the use of this medication, ask your doctor or pharmacist.

Like all medicines, this medicine may cause adverse effects, although not everyone will experience them.

The majority of adverse effects are mild or moderate. They usually appear in the first two weeks of treatment and are normally temporary.

These adverse effects include:

• Very Common Adverse Effects(may affect more than 1 in 10 people): headache.
• Common Adverse Effects(may affect up to 1 in 10 people): dizziness, drowsiness, difficulty sleeping (insomnia), nausea, diarrhea, constipation, abdominal pain, back pain, fatigue, anxiety, abnormal dreams, increased levels of liver enzymes in the blood, vomiting, weight gain.
• Uncommon Adverse Effects(may affect up to 1 in 100 people): migraine,tingling in the fingers of the hands and feet (paresthesia), blurred vision, restless legs syndrome (a disorder characterized by an irresistible urge to move the legs), tinnitus, excessive sweating (hyperhidrosis), eczema, pruritus, urticaria (hives), agitation, irritability, restlessness, aggressive behavior, nightmares, mania/hypomania (see also "Warnings and Precautions" in section 2), suicidal thoughts or behavior, confusion, weight loss, muscle pain.
• Rare Adverse Effects(may affect up to 1 in 1,000 people): severe skin rash (erythematous rash), facial edema (swelling) and angioedema (swelling of the face, lips, tongue, and/or throat that may cause difficulty breathing or swallowing), hepatitis, yellowing of the skin or white of the eyes (jaundice), liver insufficiency*, hallucinations, inability to remain still (due to physical and mental restlessness), inability to completely empty the bladder.

* A reduced number of cases led to liver transplant or death.Reporting Adverse Effects

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly through the national notification system included in theAppendix V.By reporting adverse effects, you can contribute to providing more information about the safety of this medicine.

Keep this medication out of the sight and reach of children.

Do not use this medication after the expiration date shown on the packaging and blister. The expiration date is the last day of the month indicated.

This medication does not require special storage conditions.

Medications should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the packaging and unused medications. By doing so, you will help protect the environment.

Composition of Valdoxan

• The active ingredient is agomelatine. Each film-coated tablet contains 25 mg of agomelatine.
• The other components are:

Appearance of Valdoxan and contents of the package

Valdoxan 25 mg film-coated tablets are oblong, yellow-orange tablets, with the company logo engraved in blue on one of their faces. Valdoxan 25 mg film-coated tablets are available in calendar blister packs. Packages containing 14, 28, 56, 84, or 98 film-coated tablets are available. A package of 100 film-coated tablets for hospital use is also available.

Only some package sizes may be marketed.

Marketing Authorization Holder

Les Laboratoires Servier

50, rue Carnot

92284 Suresnes cedex

France

Responsible Person for Manufacturing

Les Laboratoires Servier Industrie

905, route de Saran

45520 Gidy

France

Servier (Ireland) Industries Ltd

Gorey road

Arklow – Co. Wicklow – Ireland

Anpharm Przedsiebiorstwo Farmaceutyczne S.A.

03-236 Warszawa

ul. Annopol 6B

Poland

Laboratorios Servier, S.L.

Avda. de los Madroños, 33

28043 Madrid

Spain

For more information about this medication, please contact the local representative of the marketing authorization holder:

Last review date of this leaflet:

The detailed information about this medicine is available on the website of the European Medicines Agencyhttp://www.ema.europa.eu/.