BRINTELLIX 20 mg/ml ORAL SOLUTION DROPS

2. What you need to know before you take Brintellix

Do not take Brintellix:

• if you are allergic to vortioxetine or any of the other ingredients of this medicine (listed in section 6).
• if you are taking other medicines for depression known as monoamine oxidase inhibitors or selective MAO-A inhibitors. If in doubt, consult your doctor.

Warnings and precautions

Consult your doctor or pharmacist before taking Brintellix if:

• you are taking medicines with a serotonergic effect, such as:
• tramadol and similar medicines (strong painkillers).

• sumatriptan and similar medicines, with active ingredient names ending in "-triptan" (used to treat migraine).

• Taking these medicines with Brintellix may increase the risk of serotonin syndrome. This syndrome can be associated with hallucinations, involuntary jerks, rapid heartbeat, high blood pressure, fever, nausea, and diarrhea.
• you have had seizures.
• Your doctor will treat you with caution if you have a history of seizures or unstable/epileptic disorders. Seizures are a potential risk of medicines used to treat depression. Treatment should be discontinued in any patient who experiences seizures or an increase in their frequency.
• you have had mania.
• you have a tendency to bleed or bruise easily or if you are pregnant (see Pregnancy, breastfeeding, and fertility).
• you have low sodium levels in your blood.
• you are 65 years of age or older.
• you have severe kidney disease.
• you have severe liver disease or a liver disease called cirrhosis.
• you have increased eye pressure or glaucoma. If you experience eye pain and blurred vision during treatment, contact your doctor.

If you are receiving treatment with antidepressants, including vortioxetine, you may also experience feelings of aggression, agitation, anger, and irritability. If this happens, you should consult your doctor.

Suicidal thoughts and worsening of your depression

If you are depressed and/or suffer from anxiety disorders, you may sometimes have thoughts of harming or killing yourself. These may increase when you first start taking antidepressants, as these medicines take time to start working, usually around 2 weeks, although in some cases it may be longer.

You would be more likely to have these thoughts:

• If you have previously had thoughts of killing or harming yourself.
• If you are a young adult.

Clinical trial data have shown an increased risk of suicidal behavior in adults under 25 years of age with psychiatric disorders who were treated with an antidepressant.

If at any time you have thoughts of harming or killing yourself, contact your doctor or go directly to a hospital. It may be helpful for you to tell a relative or close friend that you are depressed or have an anxiety disorder and ask them to read this leaflet. You can ask them if they think your depression or anxiety has worsened or if they are worried about changes in your attitude.

Children and adolescents

Brintellix should not be used in pediatric patients (under 18 years of age) because its efficacy has not been established. The safety of Brintellix in children and adolescents from 7 to 17 years of age is described in section 4.

Taking Brintellix with other medicines

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.

Tell your doctor if you are taking any of the following medicines:

• phenelzine, iproniazid, isocarboxazid, nialamide, tranylcypromine (medicines for treating depression called non-selective monoamine oxidase inhibitors); you should not take any of these medicines with Brintellix. If you have taken any of these medicines, you should wait 14 days before starting to take Brintellix. After stopping Brintellix, you should wait 14 days before taking any of these medicines.
• moclobemide (a medicine for treating depression).
• selegiline, rasagiline (medicines for treating Parkinson's disease).
• linezolid (an antibiotic).
• medicines with a serotonergic effect, such as tramadol or similar medicines (strong painkillers) and sumatriptan and similar medicines with active ingredient names ending in "-triptan" (administered to treat migraine). Taking these medicines with Brintellix may increase the risk of serotonin syndrome (see section warnings and precautions).
• lithium (a medicine for treating depression and mental disorders) or tryptophan.
• medicines known to cause a decrease in sodium levels.
• rifampicin (an antibiotic).
• carbamazepine, phenytoin (a medicine for treating epilepsy or other conditions).
• warfarin, dipyridamole, phenprocoumon, some antipsychotics, phenothiazines, tricyclic antidepressants, low-dose acetylsalicylic acid, and non-steroidal anti-inflammatory drugs (anticoagulants and medicines used to relieve pain). These may increase the tendency to bleed.

Medicines that increase the risk of seizures:

• sumatriptan and similar medicines with active ingredient names ending in "-triptan".
• tramadol (a strong painkiller).
• mefloquine (an antimalarial medicine).
• bupropion (a medicine for treating depression, also used to help stop smoking).
• fluoxetine, paroxetine, and other medicines for treating depression called SSRIs/SNRIs, tricyclics.
• St. John's Wort (Hypericum perforatum) (a herbal medicine for treating depression).
• quinidine (a medicine for treating heart rhythm disorders).
• chlorpromazine, chlorprothixene, haloperidol (medicines for treating mental disorders belonging to the groups called phenothiazines, thioxanthenes, or butyrophenones).

Please talk to your doctor if you are taking any of the medicines mentioned, as your doctor needs to know if you are at risk of having seizures.

If you undergo a urine toxicology test, taking Brintellix may cause positive results for methadone when using some test methods, even though you are not taking methadone. If this happens, a more specific test can be performed.

Taking Brintellix with alcohol

It is not recommended to combine this medicine with alcohol.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor for advice before taking this medicine.

Pregnancy

Brintellix should not be used during pregnancy unless your doctor considers it absolutely necessary.

If you take medicines for depression, including Brintellix, during the last 3 months of pregnancy, you should be aware that the following effects may be seen in the newborn: breathing difficulties, blue discoloration of the skin, seizures, changes in body temperature, feeding difficulties, vomiting, low blood sugar, stiff or floppy muscles, exaggerated reflexes, tremors, nervousness, irritability, lethargy, constant crying, and sleep disturbances. If your baby shows any of these symptoms, contact your doctor immediately.

Make sure your midwife and/or doctor knows you are taking Brintellix. When taken during pregnancy, especially in the last 3 months, medicines like Brintellix may increase the risk of a serious condition in the baby called persistent pulmonary hypertension of the newborn (PPHN), making the baby breathe faster and turn blue. These symptoms usually start during the first 24 hours after birth. If this happens to your baby, you should contact your midwife and/or doctor immediately.

If you take Brintellix in the final stages of pregnancy, there may be an increased risk of heavy vaginal bleeding shortly after delivery, especially if you have a history of bleeding disorders. Your doctor or midwife should know you are taking Brintellix so they can advise you.

Breastfeeding

It is expected that the ingredients of Brintellix will pass into breast milk. Brintellix should not be used during breastfeeding. Your doctor will decide whether you should stop breastfeeding or stop using Brintellix, taking into account the benefit of breastfeeding for the child and the benefit of treatment for you.

Driving and using machines

Brintellix has little or no influence on the ability to drive or use machines. However, as dizziness has been reported, caution is recommended during these activities when starting treatment with Brintellix or changing the dose.

Brintellix contains ethanol

This medicine contains 85 mg of alcohol (96% ethanol) in each ml, which is equivalent to 10.1% v/v. The amount in 1 ml of this medicine is equivalent to less than 3 ml of beer or 1 ml of wine.

The small amount of alcohol in this medicine does not have a noticeable effect.

3. How to take Brintellix

Follow exactly the instructions for administration of this medicine given by your doctor. If you are unsure, consult your doctor or pharmacist again.

The recommended dose of Brintellix is 10 mg of vortioxetine once daily in adults under 65 years of age. Your doctor may increase the dose up to a maximum of 20 mg of vortioxetine per day or reduce it to a minimum of 5 mg of vortioxetine per day, depending on your response to treatment.

For elderly patients 65 years of age or older, the initial dose is 5 mg of vortioxetine once daily.

5 mg corresponds to 5 drops.

10 mg corresponds to 10 drops.

15 mg corresponds to 15 drops.

20 mg corresponds to 20 drops.

Method of administration

Brintellix can be taken with or without food.

The drops can be mixed with water, juice, or other non-alcoholic beverages. Brintellix oral drops should not be mixed with other medicines.

Put the bottle completely upside down. If the drops do not come out, gently tap the base of the bottle for the drops to fall.

Duration of treatment

Take Brintellix for the time your doctor has indicated.

Continue taking Brintellix even though it may take some time to start feeling better.

You should continue treatment for at least 6 months after feeling better again.

If you take more Brintellix than you should

If you take more Brintellix than you have been prescribed, consult your doctor immediately or go to the nearest hospital emergency department. Take the bottle and the remaining solution with you. Do this even if you do not feel any discomfort. The symptoms in case of overdose are: dizziness, nausea, diarrhea, stomach upset, itching all over the body, drowsiness, and flushing (redness of the skin).

After ingestion of doses several times higher than the prescribed dose, seizures (convulsions) and a rare condition called serotonin syndrome have been reported.

If you forget to take Brintellix

Take the next dose at the usual time. Do not take a double dose to make up for forgotten doses.

If you stop taking Brintellix

Do not stop taking Brintellix without consulting your doctor.

Your doctor may decide to reduce your dose before you stop taking this medicine altogether.

Some patients who have stopped taking Brintellix have experienced symptoms such as dizziness, headache, sensation of tingling or sensations similar to electric shocks (especially in the head), insomnia, nausea or vomiting, feeling of anxiety, irritability or agitation, feeling of tiredness or tremors. These symptoms may appear in the first week after stopping Brintellix.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

The side effects observed were mostly mild or moderate and occurred in the first two weeks of treatment. These effects were generally transient and did not require discontinuation of treatment.

The following side effects have been observed, with the frequencies indicated:

Very common: may affect more than 1 in 10 people

• nausea.

Common: may affect up to 1 in 10 people

• diarrhea, constipation, vomiting.
• dizziness.
• itching all over the body.
• abnormal dreams.
• increased sweating.
• indigestion.

Uncommon: may affect up to 1 in 100 people

• flushing (redness of the skin).
• night sweats.
• blurred vision.
• involuntary jerks (tremors).
• hallucinations (seeing, hearing, or feeling things that are not there).

Rare: may affect up to 1 in 1,000 people

• dilated pupils (mydriasis), which may increase the risk of glaucoma (see section 2).

Frequency not known: cannot be estimated from the available data

• low sodium levels in the blood (some of the symptoms may be a feeling of dizziness, weakness, confusion, drowsiness, or extreme tiredness, or nausea or vomiting; other more serious symptoms are fainting, seizures, or falls).
• serotonin syndrome (see section 2).
• allergic reactions, which can be severe, and cause swelling of the face, lips, tongue, or throat; difficulty breathing or swallowing, and/or a sudden drop in blood pressure (which can make you feel dizzy or faint).
• hives.
• excessive or unexplained bleeding (including bruising, nosebleeds, gastrointestinal bleeding, and vaginal bleeding).
• rash.

• sleep disorders (insomnia).

• agitation and aggression. If you experience these side effects, contact your doctor (see section 2).
• headache.

• increased levels of a hormone called prolactin in the blood.
• a constant need to move (akathisia).
• grinding teeth (bruxism).
• inability to open the mouth (trismus).
• restless legs syndrome (an irresistible urge to move the legs to stop unpleasant or uncomfortable sensations, which often occur at night).

There is an increased risk of bone fractures in patients taking this type of medicine.

Other side effects in children and adolescents

The side effects observed with vortioxetine in children and adolescents were similar to those observed in adults, except for abdominal pain-related events, which were observed more frequently in children and adolescents than in adults, and suicidal ideation, which was observed more frequently in adolescents than in adults.

Reporting of side effects

If you experience any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly through the national reporting system included in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Brintellix

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

Do not use this medicine after the expiry date which is stated on the carton after EXP. The expiry date refers to the last day of the month shown.

This medicine does not require any special storage conditions.

Once opened, the drops should be used within 8 weeks.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Packaging Contents and Additional Information

Composition of Brintellix

• The active ingredient is vortioxetine. Each drop of solution contains 1 mg of vortioxetine (as (D,L)-lactate).
• The other components are hydroxypropylbetadex, ethanol (96%) and purified water

Appearance and Packaging of the Product

Oral drops in solution

Transparent solution, almost colorless to slightly yellowish.

Brintellix oral drops in solution are available in 20 ml amber glass bottles with a screw cap and dropper (child-resistant closure).

Each bottle contains 15 ml of Brintellix oral drops in solution.

Marketing Authorization Holder and Manufacturer

• Lundbeck A/S

Ottiliavej 9

2500 Valby

Denmark

You can request more information about this medication by contacting the local representative of the marketing authorization holder:

Date of the Last Revision of this Leaflet:{MM/AAAA}

Other Sources of Information

Detailed information about this medication is available on the European Medicines Agency website: http://www.ema.europa.eu.