Varesta

Package leaflet: Information for the patient

Varesta, 5 mg, coated tablets
Varesta, 10 mg, coated tablets
Varesta, 15 mg, coated tablets
Varesta, 20 mg, coated tablets
Vortioxetine
Please read all of this leaflet carefully before taking this medicine, because it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
• If you experience any side effects, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of the leaflet

1. What Varesta is and what it is used for
2. What you need to know before taking Varesta
3. How to take Varesta
4. Possible side effects
5. How to store Varesta
6. Contents of the pack and other information

1. What Varesta is and what it is used for

Varesta contains the active substance vortioxetine. It belongs to a group of medicines called antidepressants.
Varesta is used to treat major depressive episodes in adults.
Varesta has been shown to relieve many symptoms of depression, including sadness, inner tension (feeling of anxiety), sleep disturbances (reduced amount of sleep), decreased appetite, difficulty concentrating, feelings of worthlessness, loss of interest in favourite activities, and feeling slowed down.

2. What you need to know before taking Varesta

Do not take Varesta:

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

Warnings and precautions

Before starting Varesta, talk to your doctor or pharmacist if you:

• are taking other medicines with serotonergic activity, such as:
  • tramadol and similar medicines (strong painkillers).
  • sumatriptan and similar medicines whose active substance names end in “-triptan” (used to treat migraine).

Taking these medicines together with Varesta may increase the risk of serotonin syndrome. This syndrome may include hallucinations, involuntary muscle contractions, rapid heartbeat, high blood pressure, fever, nausea, and diarrhoea.

• have had seizures (epileptic fits). Treatment will be carried out with caution if you have had seizures or if you currently have uncontrolled seizures/epilepsy. Antidepressant medicines carry a risk of seizures. Treatment should be stopped in any patient who experiences seizures for the first time or whose seizure frequency increases.
• have experienced mania.
• have a tendency to bleeding or bruising, or if you are pregnant (see "Pregnancy, breastfeeding and fertility").
• have low sodium levels in the blood.
• are 65 years of age or older.
• have severe kidney disease.
• have severe liver disease or cirrhosis of the liver.
• currently have or have previously had increased eye pressure or glaucoma. If during treatment you experience eye pain or blurred vision, contact your doctor.

Patients taking antidepressants, including vortioxetine, may also experience aggression, agitation, anger, and irritability. In such cases, talk to your doctor.

Suicidal thoughts and worsening of depression

Patients with depression and/or anxiety disorders may sometimes experience thoughts of self-harm or suicide. These thoughts may increase after starting antidepressant treatment, as all such medicines take time to work, usually about two weeks, and sometimes longer.

The risk of suicidal thoughts is higher if:

• you have previously had thoughts of self-harm or suicide.
• you are a young adult.

Clinical trial data indicate an increased risk of suicidal behaviour in adults under 25 years of age with psychiatric disorders treated with antidepressants.

If you ever experience thoughts of self-harm or suicide, contact your doctor immediately or go to hospital. It may be helpful to inform your family or friends about your depression or anxiety disorder and ask them to read this leaflet. You may ask them to inform you if they notice your depression or anxiety worsening or if they observe any concerning changes in your behaviour.

Children and adolescents

Do not use Varesta in children and adolescents (under 18 years of age) due to lack of demonstrated efficacy. The safety of Varesta in children and adolescents aged 7 to 17 years is described in section 4.

Varesta 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 used to treat depression, known as non-selective MAO inhibitors). Do not take any of these medicines together with Varesta. If you have taken any of these medicines, you must wait 14 days before starting Varesta. After stopping treatment with Varesta, you must wait 14 days before starting any of these medicines.

• moclobemide (a medicine used to treat depression).

• selegiline, rasagiline (medicines used to treat Parkinson’s disease).

• linezolid (an antibiotic used to treat bacterial infections).

• serotonergic medicines, e.g. tramadol and similar medicines (strong painkillers), and sumatriptan and similar medicines whose active substance names end in “-triptan” (used to treat migraine). Taking these medicines together with Varesta may increase the risk of serotonin syndrome (see Warnings and precautions).

• lithium (used to treat depression and psychiatric disorders) or tryptophan.

• medicines that lower sodium levels.

• rifampicin (used to treat tuberculosis and other infections).

• carbamazepine, phenytoin (medicines used to treat epilepsy and other conditions).

• warfarin, dipyridamole, phenprocoumon, certain antipsychotics, phenothiazines, tricyclic antidepressants, low-dose acetylsalicylic acid, and non-steroidal anti-inflammatory drugs (NSAIDs) (blood-thinning medicines and painkillers). These may increase the risk of bleeding.

Medicines that increase the risk of seizures:

• sumatriptan and similar medicines containing an active substance ending in “-triptan”.
• tramadol (a strong painkiller).
• mefloquine (used for prevention and treatment of malaria).
• bupropion (used to treat depression and to help people stop smoking).
• fluoxetine, paroxetine, and other antidepressants known as SSRIs/SNRIs, tricyclic antidepressants.
• St. John’s wort (Hypericum perforatum) (a herbal remedy used to treat depression).
• quinidine (used to treat heart rhythm disorders).
• chlorpromazine, chlorprothixene, haloperidol (medicines used for psychiatric disorders, belonging to the phenothiazine, thioxanthene, and butyrophenone groups).

Tell your treating doctor if you are taking any of the above medicines, as they should be aware that you are already at increased risk of seizures.

If you are undergoing urine screening tests while taking Varesta, some analytical methods may give a false positive result for methadone, even if you are not taking methadone. In such cases, a more specific test can be performed.

Taking Varesta with alcohol

Do not take 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, talk to your doctor before taking this medicine.

Pregnancy

Do not use Varesta during pregnancy unless your doctor considers it absolutely necessary.
Women who have taken antidepressants, including Varesta, during the last three months of pregnancy should be aware of the risk of the following symptoms in the newborn: breathing difficulties, bluish skin colour, seizures, changes in body temperature, feeding difficulties, vomiting, low blood sugar, muscle stiffness or floppiness, increased reflexes, tremors, shivering, irritability, lethargy, constant crying, drowsiness, and sleep difficulties. If any of these symptoms occur in the newborn, contact your doctor immediately.

Inform your midwife and/or doctor that you are taking Varesta. Medicines like Varesta taken during pregnancy, especially during the last three months, may increase the risk of a serious condition in newborns called persistent pulmonary hypertension of the newborn (PPHN), which causes the baby to breathe rapidly and have bluish skin. These symptoms usually appear within the first 24 hours after birth. If such symptoms occur, inform your midwife and/or doctor immediately.

Taking Varesta towards the end of pregnancy may increase the risk of severe vaginal bleeding shortly after delivery, especially if you have a history of bleeding disorders. If you are taking Varesta, inform your doctor or midwife so they can provide appropriate advice.

Breastfeeding

Varesta is expected to pass into human milk. Do not take Varesta while breastfeeding. Your doctor will decide whether you should stop breastfeeding or stop taking Varesta, taking into account the benefits of breastfeeding for the child and the benefits of treatment for the mother.

Driving and using machines

Varesta has no effect or negligible effect on the ability to drive and use machines. However, caution is advised when performing these activities after starting treatment with Varesta or after a dose change, as side effects such as dizziness have been reported.

Varesta contains sodium

This medicine contains less than 1 mmol (23 mg) of sodium per coated tablet, i.e. it is considered "sodium-free".

3. How to take Varesta

This medicine should always be taken as prescribed by your doctor. If in doubt, consult your
doctor or pharmacist.
The recommended dose of Varesta is 10 mg of vortioxetine as a single daily dose in adults under
65 years of age. Your doctor may increase the dose of the medicine up to a maximum of 20 mg of
vortioxetine per day or reduce it to the minimum dose of 5 mg of vortioxetine per day, depending
on the patient's response to treatment.
For people aged 65 years or older, the starting dose is 5 mg of vortioxetine once daily.
Method of administration
Take one tablet with a glass of water.
The tablet may be taken with or without food.
Duration of treatment
Continue taking Varesta for as long as your doctor recommends.
Keep taking Varesta even if you do not feel better for some time.
Treatment should be continued for at least 6 months after you start feeling better.
The 10 mg, 15 mg and 20 mg tablets may be divided into equal doses.
Taking more Varesta than prescribed
If you have taken more Varesta than prescribed, contact your doctor immediately or go to the
accident and emergency department of your nearest hospital. Take the medicine pack and any
remaining tablets with you. Do this even if you do not have any symptoms of discomfort.
Symptoms of overdose include dizziness, nausea, diarrhoea, stomach discomfort, itching of the
whole body, drowsiness and facial flushing.
After taking doses several times higher than recommended, seizures and a rare condition called
serotonin syndrome have been reported.
If you miss a dose of Varesta
Take the next dose at the usual time. Do not take a double dose to make up for the missed dose.
Stopping Varesta
Do not stop taking Varesta without consulting your doctor.
Your doctor may decide to gradually reduce the dose before stopping this medicine completely.
In some patients who stopped taking Varesta, symptoms such as dizziness, headache,
pins-and-needles sensation or an electric-shock-like feeling (especially in the head), inability to
sleep, nausea or vomiting, feeling anxious, irritable or agitated, fatigue or tremor have occurred.
These symptoms may occur within the first week after stopping Varesta.
If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
The observed adverse reactions were generally mild to moderate and occurred during the first two weeks of treatment. Reactions were usually transient and did not lead to discontinuation of treatment.

The adverse reactions listed below have been reported with the following frequencies:

Very common: may affect more than 1 in 10 people

• nausea

Common: may affect up to 1 in 10 people

• diarrhoea, constipation, vomiting
• dizziness
• itching of the skin
• unusual dreams
• excessive sweating
• indigestion

Uncommon: may affect up to 1 in 100 people

• flushing (redness of the face)
• night sweats
• blurred vision
• involuntary tremor
• hallucinations (seeing, hearing or feeling things that are not there)

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

• dilated pupils (pupil dilation), which may increase the risk of developing glaucoma (see section 2)

Frequency not known: frequency cannot be estimated from the available data

• low levels of sodium in the blood (symptoms may include dizziness, weakness, confusion, drowsiness, severe fatigue, nausea or vomiting; more serious symptoms include fainting, seizures or falls)
• serotonin syndrome (see section 2)
• allergic reactions, which may be severe, causing swelling of the face, lips, tongue or throat, difficulty breathing or swallowing, and/or sudden drop in blood pressure (causing dizziness or a feeling of emptiness in the head)
• urticaria (hives)
• excessive or unexplained bleeding (including bruising, nosebleeds, gastrointestinal bleeding and vaginal bleeding)
• rash
• sleep problems (insomnia)
• agitation and aggression. If these adverse reactions occur, contact your doctor (see section 2)
• headache
• increased levels of a hormone called prolactin in the blood
• constant need for movement (akathisia)
• teeth grinding (bruxism)
• inability to open the mouth (trismus)
• restless legs syndrome (an urge to move the legs to relieve painful or unusual sensations, often occurring at night)
• milky discharge from the breasts (galactorrhoea)

In patients taking this type of medicine, an increased risk of bone fractures has been observed.

An increased risk of sexual disorders has been reported with the 20 mg dose, and in some patients, this adverse reaction was observed even with lower doses.

Additional adverse reactions in children and adolescents

Adverse reactions of vortioxetine in children and adolescents were similar to those observed in adults, except for abdominal pain, which was reported more frequently than in adults, and suicidal thoughts, which were observed more frequently in adolescents than in adults.

Reporting of adverse reactions

If any adverse reactions occur, including any adverse reactions not listed in this leaflet, inform your doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products:

Al. Jerozolimskie 181C, 02-222 Warsaw
Tel: +48 22 49 21 301
Fax: +48 22 49 21 309
Website:

Adverse reactions can also be reported to the marketing authorization holder.

Reporting adverse reactions helps to provide more information on the safety of the medicine.

5. How to store Varesta

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the pack following the word
EXP. The expiry date refers to the last day of the stated month.
No special storage instructions are required for this medicine.
Medicines must 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. Contents of the packaging and other information

What Varesta contains

• The active substance is vortioxetine. Varesta 5 mg, coated tablets: Each coated tablet contains 5 mg of vortioxetine (as vortioxetine hydrobromide). Varesta 10 mg, coated tablets: Each coated tablet contains 10 mg of vortioxetine (as vortioxetine hydrobromide). Varesta 15 mg, coated tablets: Each coated tablet contains 15 mg of vortioxetine (as vortioxetine hydrobromide). Varesta 20 mg, coated tablets: Each coated tablet contains 20 mg of vortioxetine (as vortioxetine hydrobromide).
• The other ingredients (excipients) are: mannitol, microcrystalline cellulose, sodium carboxymethyl starch, hydroxypropyl cellulose, magnesium stearate (E470b) in the tablet core; and hypromellose, polyethylene glycol 400, titanium dioxide (E171), red iron oxide (E172) – only in 5 mg, 15 mg and 20 mg coated tablets, and yellow iron oxide (E172) – only in 10 mg and 15 mg coated tablets in the coating. See section 2 "Varesta contains sodium".

What Varesta looks like and contents of the pack
Varesta 5 mg, coated tablets (tablets)
Light grey-pink, oval, biconvex coated tablets, marked with "5" on one side.
Tablet dimensions: approximately 9 mm x 6 mm.
Varesta 10 mg, coated tablets (tablets)
Light brownish-yellow, oval, biconvex coated tablets, marked with "10" on one side and a division line on the other.
Tablet dimensions: approximately 9 mm x 6 mm.
The tablet can be divided into equal doses.
Varesta 15 mg, coated tablets (tablets)
Light brownish-orange, oval, biconvex coated tablets, marked with "15" on one side and a division line on the other.
Tablet dimensions: approximately 9 mm x 6 mm.
The tablet can be divided into equal doses.
Varesta 20 mg, coated tablets (tablets)
Brown-red, oval, biconvex coated tablets, marked with "20" on one side and a division line on the other.
Tablet dimensions: approximately 9 mm x 6 mm.
The tablet can be divided into equal doses.
Varesta is available in cardboard packaging containing:

• 14, 28, 30, 56, 60, 90 and 98 coated tablets in non-perforated or perforated blisters.

Not all pack sizes may be marketed.
Marketing Authorisation Holder and Manufacturer
KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia
For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:
KRKA-POLSKA Sp. z o.o.
ul. Równoległa 5
02-235 Warszawa
Tel. 22 57 37 500