ZARELIS 75 mg Extended-Release Tablet

Зміст інструкції

1. Zarelis 37.5 mg Extended-Release Tablet, 75 mg Extended-Release Tablet, 150 mg Extended-Release Tablet, 225 mg Extended-Release Tablet
   1. What is Zarelis and what is it used for
   2. What you need to know before taking Zarelis
   3. How to take Zarelis
   4. Possible Undesirable Effects
   5. How to store Zarelis
   6. Package contents and other information
2. Zarelis 300 mg Extended-release tablet
   1. What is Zarelis and what it is used for
   2. What you need to know before taking Zarelis
   3. How to take Zarelis
   4. Possible side effects
   5. How to store Zarelis
   6. Package contents and other information

Zarelis 37.5 mg Extended-Release Tablet, 75 mg Extended-Release Tablet, 150 mg Extended-Release Tablet, 225 mg Extended-Release Tablet

Venlafaxine

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

• Keep this leaflet. 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 the same symptoms as you, as it could be harmful.
• If you get any side effects, even those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What is Zarelis and what is it used for

Zarelis contains the active ingredient venlafaxine
Zarelis is an antidepressant belonging to a group of medicines called serotonin and noradrenaline reuptake inhibitors (SNRIs). This group of medicines is used
for the treatment of depression and other conditions, such as anxiety disorders. It is believed that
people who are depressed and/or anxious have lower levels of serotonin and noradrenaline in the
brain. It is not fully understood how antidepressants work, however they can
be helpful by raising the levels of serotonin and noradrenaline in the brain.
Zarelis is a treatment for adults suffering from depression. Zarelis is also a treatment for adults
with the following anxiety disorders: generalized anxiety disorder, social anxiety disorder (fear of or
tendency to avoid social situations) and panic disorder (panic attacks). Appropriate
treatment of depression or anxiety disorders is important to help you feel better. If not
treated, your condition may not resolve and may become more severe and more difficult to treat.

2. What you need to know before taking Zarelis

Do not take Zarelis

• if you are allergic to venlafaxine or any of the other ingredients of this medicine (listed in section 6).
• if you are taking, or have taken within the last 14 days, any medicines known as irreversible monoamine oxidase inhibitors (IMAO), used to treat depression or Parkinson's disease. Taking an irreversible IMAO with Zarelis may cause serious or even life-threatening side effects. You must also wait at least 7 days after stopping treatment with Zarelis before taking any irreversible IMAO (also see

the section entitled “Other medicines and Zarelis” and the information contained in that
section relating to “Serotonin syndrome”).

Warnings and precautions
Talk to your doctor or pharmacist before taking Zarelis.

• If you are taking other medicines that, when taken with Zarelis, may increase the risk of developing serotonin syndrome (see the section “Other medicines and Zarelis”)
• If you have difficulty swallowing, stomach or intestinal disorders that reduce the ability to swallow or pass food with normal intestinal movements. If you have eye problems, such as certain types of glaucoma (increased pressure inside the eye)
• If you have a history of high blood pressure
• If you have a history of heart problems
• If you have been told you have an abnormal heart rhythm
• If you have a history of seizures
• If you have a history of low sodium levels in your blood (hyponatremia)
• If you have a tendency to bruise easily or a tendency to bleed easily (bleeding disorders), if you are using other medicines that may increase the risk of bleeding, e.g. warfarin (used to prevent blood clots), or if you are pregnant (see "Pregnancy and breastfeeding").
• If you have a history of mania or bipolar disorder (feeling overexcited or euphoric)
• If you have a history of aggressive behaviour.
• Bla bla Zarelis may cause a feeling of restlessness or inability to sit still during the first few weeks of treatment. If you experience these symptoms, you should tell your doctor. Suicidal thoughts and worsening of your depression or anxiety disorder If you are depressed and/or suffer from anxiety disorders, you may sometimes have thoughts of harming yourself or committing suicide. These may increase when you start using antidepressants for the first time, as it takes time for these medicines to start working, usually about two weeks but sometimes longer. These thoughts may also occur when the dose is reduced or during discontinuation of Zarelis treatment. You are more likely to have these thoughts:
• If you have had previous thoughts of suicide or self-harm.
• If you are young. Information obtained from clinical studies has shown an increased risk of suicidal behaviour in young people (under 25 years of age) with psychiatric disorders who had been treated with an antidepressant.

If at any time you have thoughts of harming yourself or committing suicide, contact your doctor or go
to the nearest hospital immediately.
It may help to tell a relative or close friend that you are depressed or suffering from an
that your depression or anxiety is getting worse, or if you are concerned about changes
in your behaviour.
Dry mouth
Dry mouth occurs in 10% of patients treated with venlafaxine. This may increase
the risk of tooth decay. You should therefore pay particular attention to your oral hygiene.
Diabetes
Blood glucose levels may be altered by the use of Zarelis. Therefore, the dosages of your
diabetes medicines may need to be adjusted.
Sexual dysfunction
Medicines such as Zarelis (so-called selective serotonin reuptake inhibitors SSRIs and serotonin and noradrenaline reuptake inhibitors SNRIs) can cause symptoms of sexual dysfunction (see
section 4). In some cases, these symptoms have been observed to persist after discontinuation of
treatment .
Children and adolescents
Zarelis is normally not to be used for children and adolescents under 18 years of age.
In addition, you should know that patients under 18 years of age have a greater risk of side
effects, such as suicide attempts, suicidal thoughts and hostility (mainly aggression,
oppositional behaviour and anger) when taking this type of medicine. Despite this, the
doctor may prescribe this medicine for patients under 18 years of age because they believe that
this is in their best interest. If the doctor has prescribed this medicine to a patient with
less than 18 years of age, and you want to discuss this, talk to your doctor. You should tell your doctor if you
experience or worsen any of the symptoms listed above when a patient under 18
years of age is taking Zarelis. Furthermore, the long-term effects of this
medicine on growth, maturation and mental and behavioural development in this age group have not been demonstrated.

Other medicines and Zarelis
Tell your doctor or pharmacist if you are taking, have recently taken or might take
any other medicines.
The doctor will decide whether you can use Zarelis with other medicines.
Do not start or stop taking other medicines, including medicines you obtain without
prescription and herbal or traditional medicines, before asking your doctor or pharmacist.

• Monoamine oxidase inhibitors that are used to treat depression or Parkinson's disease must not be taken with Zarelis. Tell your doctor if you have taken these medicines in the last 14 days (IMAOs: see the section “What you need to know before taking Zarelis”).
• Serotonin syndrome: A potentially life-threatening condition or reactions of the type Neuroleptic Malignant Syndrome (see the section “Possible side effects”) may occur with venlafaxine treatment, especially when it is taken with other medicines. Examples of these medicines are:
• Triptans (used for migraine)
• Other medicines for the treatment of depression, for example serotonin and noradrenaline reuptake inhibitors (SNRIs, SSRIs), tricyclic antidepressants, or medicines containing lithium
• Medicines containing amphetamines (used for the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy and obesity)
• Medicines containing linezolid, an antibiotic (used to treat infections)
• Medicines containing moclobemide, an IMAO (used to treat depression)
• Medicines containing sibutramine (used for weight loss)
• Medicines containing tramadol, fentanyl, tapentadol, pethidine or pentazocine (used to treat severe pain)
• Medicines containing dextromethorphan (Used for the treatment of cough)
• Medicines containing methadone (used for the treatment of opioid substance dependence or severe pain)
• Medicines containing methylene blue (used to treat high levels of methemoglobin in the blood)
• St John's wort preparations (also called Hypericum Perforatum,a remedy based on a medicinal plant used to treat mild depression)
• Products containing tryptophan (used for disorders such as sleep disorders and depression)
• Antipsychotics (used to treat symptoms such as hearing, seeing or perceiving things that do not exist, having false beliefs, unusual distrust, unusual suspicion or confused thinking, or detachment)

Signs and symptoms of serotonin syndrome may include a combination of: restlessness,
hallucinations, loss of coordination, rapid heartbeat, increased body temperature,
rapid fluctuations in blood pressure, hyperactive reflexes, diarrhea, coma, nausea, vomiting.
In its most severe form, serotonin syndrome can manifest as neuroleptic
malignant syndrome (NMS). Signs and symptoms of NMS may include fever, acceleration
of the heartbeat, sweating, severe muscle rigidity, confusion and increased muscle enzymes
(assessed through a blood test).

Immediately inform your doctor, or go to the nearest hospital emergency room if
you think you have serotonin syndrome.
You must inform your doctor if you are taking medicines that can affect the heart rate.
Examples of these medicines include:

• Antiarrhythmics such as quinidine, amiodarone, sotalol or dofetilide (used to treat abnormal heart rhythm)
• Antipsychotics such as thioridazine (see also above: Serotonin Syndrome)
• Antibiotics such as erythromycin or moxifloxacin (used to treat bacterial infections)
• Antihistamines (used to treat allergies)

The following medicines may also interfere with Zarelis and must be used with
caution. It is particularly important that you tell your doctor or pharmacist if you are using
medicines that contain:

• ketoconazole, (an antifungal medicine)
• haloperidol or risperidone (for the treatment of psychiatric disorders)
• metoprolol (a beta-blocker for the treatment of high blood pressure and heart problems).

Zarelis with food, drinks and alcohol
You should take Zarelis with food (see the section “How to take Zarelis”).
You should not drink alcohol while taking Zarelis.

Pregnancy and breastfeeding
If you are pregnant, suspect you are pregnant or are planning a pregnancy, ask your doctor or
pharmacist for advice before using this medicine.
You should only use Zarelis after discussing the potential benefits and potential risks
to the fetus with your doctor.
Make sure your midwife and/or your doctor knows that you are taking Zarelis. If taken
during pregnancy, similar medicines (SSRIs) may increase the risk of a serious condition
in babies, called persistent pulmonary hypertension of the newborn (PPHN), which causes
accelerated breathing in the baby and a bluish skin colour. These symptoms usually occur
within the first 24 hours after the baby's birth. If this happens to your baby, you should
contact your midwife and/or doctor immediately.
If you are using Zarelis near the end of pregnancy, there may be an increased risk of
heavy vaginal bleeding shortly after delivery, especially if you suffer from bleeding disorders
(easy bleeding). Inform your doctor or midwife/obstetrician that you are
taking Zarelis, so they can advise you on what to do.
Zarelis is excreted in breast milk. There is a risk of effects of the drug on the breastfed baby.
Therefore, you should discuss this with your doctor, who will decide whether to stop breastfeeding or
therapy with this medicine.

Driving and using machines
Do not drive and do not use tools or machines until you understand what effects this medicine has on
you.

Zarelis contains lactose
This medicine contains lactose. If you have been diagnosed with intolerance to some
sugars, contact your doctor before taking this medicine.

3. How to take Zarelis

Take this medicine following exactly the instructions of your doctor. If you have any doubts, ask your
doctor or pharmacist.
The usual starting dose recommended for the treatment of depression, and generalized anxiety
disorder and social anxiety disorder is 75 mg per day. Your doctor may gradually increase the dose
and, if necessary, up to a maximum dose of 375 mg per day for depression.
If you are being treated for panic disorder, your doctor will start with a lower dose (37.5 mg) and
then gradually increase the dose. The maximum dose for generalized anxiety
disorder, social anxiety disorder and panic disorder is 225 mg per day.
Take Zarelis at about the same time each day, in the morning or evening. The tablets must be
swallowed whole with a liquid and must not be opened, broken, chewed or dissolved.
You must take Zarelis with food.
If you have liver or kidney problems, talk to your doctor, as an adjustment
of the dose of this medicine may be necessary.
Do not stop treatment with this medicine without consulting your doctor (see the
paragraph “If you stop taking Zarelis”).

If you take more Zarelis than you should
Contact your doctor or pharmacist immediately if you take more medicine than you have been
prescribed by your doctor.
Symptoms of a possible overdose may include increased heart rate,
changes in state of consciousness (ranging from drowsiness to coma), blurred vision, seizures
and vomiting.

If you forget to take Zarelis
If you forget to take a dose, take it as soon as you remember. However, if you are due to take the
next dose when you remember the forgotten dose, skip the forgotten dose and take one
dose as usual. Do not take a double dose to make up for a forgotten dose
Do not take more than the amount of Zarelis prescribed for that day in a single day.

If you stop taking Zarelis
Do not stop treatment or reduce the dose without your doctor's advice, even if you feel
better. If your doctor thinks you no longer need Zarelis, they may ask you to reduce the dose
gradually before stopping treatment completely. It is known that undesirable effects occur when patients stop treatment with this medicine, especially when it is
stopped abruptly or when the dose is reduced too quickly. Some patients may experience
symptoms such as fatigue, dizziness, confusion, headache, insomnia, nightmares, dryness of the mouth, loss of appetite, nausea, diarrhea, nervousness, agitation, confusion, tinnitus (ringing in the
ears), tingling or rarely sensations of electric shock, weakness, sweating, seizures or
flu-like symptoms, vision problems and increased blood pressure (which can
cause headache, dizziness, ringing in the ears, sweating, etc.).
Your doctor will explain how you should gradually stop treatment with Zarelis. This
may take a period of several weeks or months. In some patients it may be necessary
to stop treatment very gradually over periods of months or more.
If you experience any of these or other symptoms that bother you, consult your doctor for
further advice.
If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4. Possible Undesirable Effects

Like all medicines, this medicine can cause undesirable effects, although not everyone will experience them.
If you experience any of the following effects, do not take any more Zarelis. Contact your doctor
immediately, or go to the nearest hospital emergency room.

Uncommon (may affect up to 1 in 100 people)

• Swelling of the face, mouth, tongue, throat, hands or feet, and/or itchy rash, difficulty swallowing or breathing

Rare (may affect up to 1 in 1000 people)

• Chest tightness, wheezing, difficulty swallowing or breathing
• Severe rash, itching, urticaria (raised, red or pale skin patches that often itch)
• Signs and symptoms of serotonin syndrome which may include restlessness, hallucinations, loss of coordination, increased heart rate, increased body temperature, rapid changes in blood pressure, overactive reflexes, diarrhea, coma, nausea, vomiting. In its most severe form, serotonin syndrome can manifest as Neuroleptic Malignant Syndrome (NMS). The signs and symptoms of NMS may include fever, increased heart rate, sweating, severe muscle rigidity, confusion, and increased muscle enzymes (evaluated through a blood test).
• Signs of infection, such as high body temperature, chills, shivering, headache, sweating, flu-like symptoms. This could be a result of blood disorders that could lead to an increased risk of

infection.

• Severe rash, which can lead to blistering and severe skin peeling.
• Unexplained muscle pain, tenderness or weakness. This could be a sign of rhabdomyolysis Frequency not known (cannot be estimated from the available data)
• Signs and symptoms of a condition called “stress cardiomyopathy” which may include chest pain, shortness of breath, dizziness, fainting, irregular heartbeat.

Other undesirable effects, about which you should inform your doctor, include (the frequencies of these
undesirable effects are included in the list below “Other undesirable effects that may
occur”):

• Cough, wheezing and difficulty breathing which may be accompanied by fever
• Black (tarry) stools or blood in the stools
• Itching, yellowing of the skin or eyes, itching, dark urine, which may be symptoms of liver inflammation (hepatitis)
• Heart problems, such as fast or irregular heartbeat, increased blood pressure
• Eye problems, such as blurred vision, dilated pupils
• Nervous system problems, such as dizziness, tingling, movement disorders (muscle stiffness or spasms), convulsions
• Psychiatric problems, such as hyperactivity and feeling unusually excited
• Withdrawal symptoms (see section “How to take Zarelis, if you stop taking Zarelis”)
• Prolonged bleeding - if you cut or injure yourself, it may take longer than usual for the bleeding to stop.

Do not be concerned if you see a tablet in your stool after taking Zarelis. As the tablet
travels the length of the gastrointestinal tract, the venlafaxine is released slowly. The
tablet form remains undissolved and is eliminated in the stool. Therefore, even if you can
see a tablet in your stool, the dose of venlafaxine has been absorbed.
Other undesirable effects that may occur

Very common (may affect more than 1 in 10 people)

• Dizziness; headache; drowsiness
• Insomnia
• Nausea; dry mouth, constipation
• Sweating (including night sweats)

Common (may affect up to 1 in 10 people)

• Decreased appetite
• Confusion; feeling detached (or estranged) from oneself; anorgasmia; decreased libido; agitation; Nervousness; abnormal dreams
• Tremor, a feeling of restlessness or inability to sit still or remain immobile. tingling; altered taste; increased muscle tone
• Visual disturbances, including blurred vision; dilated pupils; inability of the eye to focus on objects, from far to near
• Ringing in the ears (tinnitus)
• Fast heartbeat; palpitations
• Increased blood pressure; flushing
• Shortness of breath; yawning
• Vomiting; diarrhea
• Moderate rashes; itching
• Increased frequency of the need to urinate; inability to urinate; difficulty urinating
• Menstrual irregularities such as increased bleeding, or increased irregular bleeding; Abnormal ejaculation/orgasm (in males); erectile dysfunction (impotence)
• Weakness (asthenia); fatigue; chills
• Weight gain; weight loss
• Increased cholesterol

Uncommon (may affect up to 1 in 100 people)

• Hyperactivity, racing thoughts and reduced need for sleep (mania)
• Hallucinations; feeling of detachment from reality; abnormal orgasm; absence of sensations or emotions; feeling of overstimulation; teeth grinding
• Fainting; involuntary muscle movements; impaired coordination and balance
• Feeling of dizziness (especially when getting up too quickly); low blood pressure
• Vomiting blood, presence of tarry stools or blood in the stools, which may be a symptom of intestinal bleeding
• Sensitivity to sunlight; bruising; abnormal hair loss
• Inability to control urination
• Rigidity, spasms and involuntary movements of the muscles
• Small changes in blood levels of liver enzymes

Rare (may affect up to 1 in 1,000 people)

• Convulsions or seizures
• Cough, wheezing, shortness of breath which may be accompanied by fever
• Disorientation and confusion often accompanied by hallucinations (delirium)
• Excessive intake of water (known as SIADH)
• Decreased blood levels of sodium
• Intense eye pain and decreased or blurred vision
• Abnormal, fast or irregular heartbeat, which can lead to fainting
• Intense abdominal or back pain (which may indicate a serious problem with the intestine, liver or pancreas)
• Itching, yellowing of the skin and eyes, dark urine, or flu-like symptoms, which are symptoms of liver inflammation (hepatitis)

Very rare (may affect up to 1 in 10,000 people)

• Prolonged bleeding, which could lead to a reduction in platelets in the blood, leading to an increased risk of bruising or bleeding
• Abnormal secretion of breast milk
• Unexpected bleeding, such as bleeding gums, blood in the urine or vomit, or unexpected appearance of bruises or broken blood vessels (spider veins)

Not known (frequency cannot be estimated from the available data)

• Suicidal ideation and suicidal behaviors; cases of suicidal ideation and suicidal behaviors have been reported during therapy with venlafaxine or immediately after discontinuation of treatment (see section 2 “What you need to know before taking Zarelis”)
• Aggression
• Vertigo
• Abundant vaginal bleeding shortly after childbirth (postpartum hemorrhage), see section 2, Pregnancy and breastfeeding, for further information.

Sometimes Zarelis causes undesirable effects that you may not notice, such as increases in blood
pressure or abnormal heartbeat; slight changes in blood levels of liver enzymes, sodium or
cholesterol. Less frequently, Zarelis can reduce the function of platelets in your blood,
resulting in an increased risk of bruising and bleeding. Therefore, on occasion your
doctor may want to have blood tests done, especially if you have been taking Zarelis for a long time.
If you experience any undesirable effect, inform your doctor or pharmacist. This includes

Reporting of undesirable effects
If you experience any undesirable effect, including those not listed in this leaflet, please
contact your doctor or pharmacist. You can also report undesirable effects directly through the
national reporting system at https://www.aifa.gov.it/content/segnalazioni-
reazioni-avverse .. Reporting undesirable effects can help provide more information
about the safety of this medicine.

5. How to store Zarelis

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 packaging. The expiry date refers to the last day of that month.
This medicine does not require any particular storage temperature.
Blister: Store in the original packaging to protect the medicine from moisture.
Plastic bottle: Keep the bottle tightly closed to protect the medicine from moisture.
Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Zarelis contains
The active ingredient is venlafaxine.
Each Zarelis extended-release tablet of 37.5, 75, 150 or 225 mg contains venlafaxine
hydrochloride corresponding to 37.5 mg, 75 mg, 150 mg or 225 mg of venlafaxine.
The other ingredients are:
Tablet core: Mannitol (E421), Povidone K-90, Macrogol 400, Microcrystalline Cellulose,
Anhydrous colloidal silica, Magnesium stearate.
Tablet coating: Cellulose acetate, Macrogol 400, Opadry Y 30 18037 (mixture of
hypromellose, lactose monohydrate, titanium dioxide (E171) and triacetin).

Description of Zarelis and package contents
37.5 mg extended-release tablets: round, biconvex, white tablets with a diameter of 7
mm
75 mg extended-release tablets: round, biconvex, white tablets with a diameter of 7.5
mm
150 mg extended-release tablets: round, biconvex, white tablets with a diameter of 9.5
mm
225 mg extended-release tablets: round, biconvex, white tablets with a diameter of 11
mm
Zarelis is available in blisters of 10, 14, 20, 28, 30, 50, 56, 60, 100 and 500 tablets; and in plastic
bottles of 10, 14, 20, 28, 30, 50, 56, 60, 100 and 500 tablets.
Not all pack sizes may be marketed

Marketing Authorisation Holder
Italfarmaco S.p.A.
Viale F. Testi, 330, 20126 - Milan
Tel: +39.02.64431
Fax: +39.02.644346
e-mail: [email protected]

Manufacturer:
Laboratorios LICONSA, S.A.
Avda. Miralcampo, Nº 7, Polígono Industrial Miralcampo
19200 Azuqueca de Henares (Guadalajara), SPAIN
Italfarmaco S.p.A.
Viale F. Testi, 330
20126 Milan - Italy

This medicinal product is authorised in the Member States of the EEA under the following names:
Sweden: Venlafaxin 1A Farma 37.5/75/150/225 mg prolonged-release tablet
Estonia: Venlafaxine Liconsa 37.5/75/150/225 mg, toimeainet prolongeeritult vabastavad tabletid
Greece: Serosmine Δισκίο παρατεταμένης αποδέσμευσης 37.5/75/150/225 mg/TAB
France: VENLAFAXINE BIPHAR 37.5/75/150/225 mg prolonged-release tablet
Italy: Zarelis 37.5/75/150/225 mg Extended-release tablet
Netherlands: Venlafaxine Liconsa 37.5/75/150 mg Tablet with extended release
Venlafaxine Aurobindo 225 mg, Tablet with extended release
Poland: Axyven
Portugal: Zarelix 37.5/75/150/225 mg prolonged-release tablets
UK: Venlalic XL 37.5/75/150/225 mg prolonged-release tablets

Zarelis 300 mg Extended-release tablet

Venlafaxine

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

• Keep this leaflet. 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 their symptoms are the same as yours because it may be harmful.
• If you get any side effects, even those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet:

• 7. What Zarelis is and what it is used for
• 8. What you need to know before you take Zarelis
• 9. How to take Zarelis
• 10. Possible side effects
• 11. How to store Zarelis
• 12. Contents of the pack and other information

3. What is Zarelis and what it is used for

Zarelis contains the active ingredient venlafaxine which is an antidepressant belonging to a group of
medicines called serotonin and noradrenaline reuptake inhibitors (SNRI).
This group of medicines is used for the treatment of depression and other conditions,
such as anxiety disorders. It is believed that people who are depressed and/or anxious have lower
levels of serotonin and noradrenaline in the brain. The way antidepressants work is not fully understood,
however they can help by raising the levels of serotonin and
noradrenaline in the brain.
Zarelis is a treatment for adults suffering from depression. Appropriate treatment of
depression is important to help you feel better. If left untreated, your condition may not
resolve and may become more serious and more difficult to treat.

4. What you need to know before taking Zarelis

Do not take Zarelis

• if you are allergic to venlafaxine or any of the other ingredients of this medicine (listed in section 6).
• if you are taking, or have taken within the last 14 days, any medicines known as irreversible monoamine oxidase inhibitors (IMAO), used to treat depression or Parkinson's disease. Taking an irreversible MAOI with Zarelis may cause serious or even life-threatening side effects. You must also wait at least 7 days after stopping treatment with venlafaxine before taking any irreversible MAOI (also see the section entitled “Other medicines and Zarelis” and the information contained in that section regarding “Serotonin Syndrome”).

Warnings and precautions
Talk to your doctor or pharmacist before taking Zarelis.

• If you are using other medicines that, when taken with Zarelis, may increase the risk of developing serotonin syndrome (see the section “Other medicines and Zarelis”)
• If you suffer from problems with swallowing, the stomach or intestines that reduce the ability to swallow or pass food with normal intestinal movements
• If you have eye problems, such as certain types of glaucoma (increased pressure inside the eye)
• If you have a history of high blood pressure
• If you have a history of heart problems
• If you have been told you have an abnormal heart rhythm
• If you have a history of seizures
• If you have a history of low sodium levels in your blood (hyponatremia)
• If you have a tendency to bruise easily or a tendency to bleed easily (bleeding disorders), if you are using other medicines that may increase the risk of bleeding, e.g. warfarin (used to prevent blood clots), or if you are pregnant (see “Pregnancy and breastfeeding”)
• If you have a history of mania or bipolar disorder (feeling overexcited or euphoric)
• If you have a history of aggressive behaviour. Zarelis may cause a feeling of restlessness or inability to sit still or remain calm during the first weeks of treatment. If you experience these symptoms, you should tell your doctor.

Suicidal thoughts and worsening of your depression
If you are depressed, you may sometimes have thoughts of harming yourself or committing suicide. These may increase
when you first start taking antidepressants, as it takes time for these types of medicines to start working, usually about two weeks but sometimes longer. These thoughts may also occur when the dose is reduced or when stopping treatment with Zarelis.
You are more likely to have these thoughts:

• If you have had thoughts of suicide or self-harm in the past.
• If you are young. Information obtained from clinical studies has shown an increased risk of suicidal behaviour in young people (under 25 years of age) with psychiatric disorders who had been treated with an antidepressant.

If at any time you have thoughts of harming yourself or committing suicide, contact your doctor or go
to the nearest hospital immediately.
It may help to tell a relative or close friend that you are depressed and ask them to watch out for
any changes in your behaviour that concern them.
Dry mouth
Dry mouth occurs in 10% of patients treated with venlafaxine. This may increase the
risk of tooth decay. Therefore, you should pay particular attention to your oral hygiene.
Diabetes
Blood glucose levels may be altered by the use of Zarelis. Therefore, the dosages of your
diabetes medicines may need to be adjusted.
Sexual dysfunction
Medicines such as Zarelis (so-called selective serotonin reuptake inhibitors SSRIs and
serotonin and noradrenaline reuptake inhibitors SNRIs) can cause symptoms of sexual dysfunction (see
section 4). In some cases, these symptoms have been observed to persist after discontinuation of
treatment .
Children and adolescents
Zarelis is normally not used for children and adolescents under the age of 18 years.
In addition, you should know that patients under the age of 18 years have an increased risk of side
effects, such as suicide attempts, suicidal thoughts and hostility (mainly aggressiveness,
oppositional behaviour and anger) when taking this type of medicine. Despite this, the
doctor may prescribe this medicine for patients under the age of 18 years, because they believe that
this is in their best interest. If the doctor has prescribed this medicine to a patient under the age of 18 years, and you want to discuss this, talk to your doctor. You should inform your doctor if any of the symptoms listed above occur or worsen when a patient under the age of 18
years is taking venlafaxine. Furthermore, the long-term effects of this
medicine on growth, maturation and mental and behavioural development in this age group have not been demonstrated.

Other medicines and Zarelis
Tell your doctor or pharmacist if you are taking, have recently taken or might take
any other medicines.
The doctor will decide whether you can use Zarelis with other medicines.
Do not start or stop taking other medicines, including medicines you obtain without
a prescription and herbal remedies or traditional medicines, before asking your
doctor or pharmacist.

• Monoamine oxidase inhibitors that are used to treat depression or Parkinson's disease must not be taken with venlafaxine. Tell your doctor if you have taken these medicines in the last 14 days (MAOIs: see the section “What you need to know before taking Zarelis”).
• Serotonin Syndrome: A potentially life-threatening condition or reactions of the type Neuroleptic Malignant Syndrome (see the section “Possible side effects”) may occur with treatment with venlafaxine, especially when it is taken with other medicines. Examples of these medicines are:
• Triptans (used for migraine)
• Other medicines for the treatment of depression, for example serotonin reuptake inhibitors and noradrenaline (SNRIs, SSRIs), tricyclic antidepressants, or medicines containing lithium
• Medicines containing amphetamines (used for the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy and obesity)
• Medicines containing linezolid, an antibiotic (used to treat infections)
• Medicines containing moclobemide, an MAOI (used to treat depression)
• Medicines containing sibutramine (used for weight loss)
• Medicines containing tramadol, fentanyl, tapentadol, pethidine, or pentazocine (used to treat severe pain)
• Medicines containing dextromethorphan (Used for the treatment of cough)
• Medicines containing methadone (used for the treatment of opioid substance dependence or severe pain)
• Medicines containing methylene blue (used to treat high levels of methaemoglobin in the blood)
• Preparations based on St. John's wort (also called Hypericum Perforatum,a remedy based on

a medicinal plant used to treat mild depression)

• Products containing tryptophan (used for sleep disorders and depression)
• Antipsychotics (used to treat symptoms such as hearing, seeing or perceiving things that do not exist, having false beliefs, unusual distrust, unusual suspicion or confused thinking, or detachment)

Signs and symptoms of serotonin syndrome may include a combination of: restlessness,
hallucinations, loss of coordination, rapid heartbeat, increased body temperature,
rapid fluctuations in blood pressure, overactive reflexes, diarrhoea, coma, nausea, vomiting.
In its most severe form, serotonin syndrome can manifest as neuroleptic malignant syndrome (NMS). Signs and symptoms of NMS may include fever, acceleration
of the heartbeat, sweating, severe muscle rigidity, confusion and increased muscle enzymes (assessed through a blood test).

Immediately inform your doctor, or go to the nearest hospital emergency room if
you think you have serotonin syndrome.
You must inform your doctor if you are taking medicines that may affect your heart rhythm.
Examples of these medicines include:

• Antiarrhythmics such as quinidine, amiodarone, sotalol or dofetilide (used to treat abnormal heart rhythm)
• Antipsychotics such as thioridazine (see also above: Serotonin Syndrome)
• Antibiotics such as erythromycin or moxifloxacin (used to treat bacterial infections)
• Antihistamines (used to treat allergies)

The following medicines may also interfere with Zarelis and must be used with
caution. It is particularly important that you tell your doctor or pharmacist if you are using
medicines that contain:

• ketoconazole, (an antifungal medicine)
• haloperidol or risperidone (for the treatment of psychiatric disorders)
• metoprolol (a beta-blocker for the treatment of high blood pressure and heart problems).

Zarelis with food, drinks and alcohol
You should take venlafaxine with food (see the section “How to take Zarelis”).
You should not drink alcohol while taking Zarelis.

Pregnancy and breastfeeding
If you are pregnant, suspect you are pregnant, are planning to become pregnant or are breastfeeding,
ask your doctor or pharmacist for advice before using this medicine.
You should only use Zarelis after discussing the potential benefits and risks
to the fetus with your doctor.
Make sure your midwife and/or doctor knows that you are taking Zarelis. If taken
during pregnancy, similar medicines (SSRIs) may increase the risk of a serious condition
in babies, called persistent pulmonary hypertension of the newborn (PPHN), which causes
accelerated breathing in the baby and a bluish skin colour. These symptoms usually occur
within the first 24 hours after the baby's birth. If this happens to your baby, you should
contact your midwife and/or doctor immediately.
If you are taking Zarelis near the end of pregnancy, there may be an increased risk of
heavy bleeding shortly after delivery, especially if you suffer from bleeding disorders (easy
bleeding). Inform your treating doctor or midwife/obstetrician that you are taking Zarelis
so that they can advise you on what to do.
Zarelis is excreted in breast milk. There is a risk of effects on the breastfed baby.
Therefore, you should discuss this with your doctor, who will decide whether to stop
breastfeeding or the treatment with this medicine.

Driving and using machines
Do not drive and do not use tools or machines until you understand how this medicine affects
you.

Zarelis contains lactose.
If you have been diagnosed with intolerance to certain sugars, contact your doctor before taking
this medicine.

3. How to take Zarelis

Take this medicine following exactly the instructions of your doctor. If you have any doubts, ask your
doctor or pharmacist.
The usual starting dose recommended for the treatment of depression is 75 mg per day. The
doctor may gradually increase the dose and, if necessary, up to a maximum dose of 375
mg per day.
Take Zarelis at about the same time each day, in the morning or evening. The tablet must be swallowed
whole with a liquid and must not be broken, chewed or dissolved.
You must take Zarelis with food.
If you have liver or kidney problems, talk to your doctor, as a dose adjustment of venlafaxine may be necessary.
Do not stop treatment with Zarelis without consulting your doctor (see section “If you stop taking Zarelis”).

If you take more Zarelis than you should
Contact your doctor or pharmacist immediately if you take more medicine than prescribed by your
doctor.
Symptoms of a possible overdose may include increased heart rate, changes in consciousness (ranging from
drowsiness to coma), blurred vision, seizures and vomiting.

If you forget to take Zarelis
If you forget to take a dose, take it as soon as you remember. However, if you are due to take the
next dose when you remember the forgotten dose, skip the forgotten dose and take one dose as usual. Do
not take a double dose to make up for a missed dose. Do not take more than the amount of Zarelis
prescribed for that day in one day.

If you stop taking Zarelis
Do not stop treatment or reduce the dose without your doctor's advice, even if you feel
better. If your doctor thinks you no longer need Zarelis, they may ask you to reduce the dose
gradually before stopping treatment completely. It is known that side effects occur when patients stop
taking this medicine, especially when it is stopped abruptly or when the dose is reduced too quickly. Some
patients may experience symptoms such as fatigue, dizziness, confusion, headache, insomnia, nightmares,
dry mouth, loss of appetite, nausea, diarrhea, nervousness, agitation, confusion, tinnitus (ringing in the
ears), tingling or rarely sensations of electric shock, weakness, sweating, seizures or
flu-like symptoms, vision problems and increased blood pressure (which can
cause headache, dizziness, ringing in the ears, sweating, etc.).
Your doctor will explain how to gradually stop treatment with Zarelis. This
may take several weeks or months. In some patients, it may be necessary
to stop treatment very gradually over months or longer.
If you experience any of these or other symptoms that bother you, seek your doctor's advice.
If you have any further questions on 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 everyone will experience them.
If you experience any of the following effects, do not take any more Zarelis. Contact your
doctor immediately, or go to the nearest hospital emergency room.

Uncommon (may affect up to 1 in 100 people)

• Swelling of the face, mouth, tongue, throat, hands or feet, and/or itchy rash, difficulty swallowing or breathing

Rare (may affect up to 1 in 1,000 people)

• Chest tightness, wheezing, difficulty swallowing or breathing
• Severe rash, itching, hives (raised, red or pale skin patches that often itch)
• Signs and symptoms of serotonin syndrome which may include restlessness, hallucinations, loss of coordination, increased heart rate, increased body temperature, rapid changes in blood pressure, overactive reflexes, diarrhea, coma, nausea, vomiting. In its most severe form, serotonin syndrome can manifest as Neuroleptic Malignant Syndrome (NMS). The signs and symptoms of NMS may include fever, increased heart rate, sweating, severe muscle rigidity, confusion, and increased muscle enzymes (assessed through a blood test).
• Signs of infection, such as high body temperature, chills, shaking, headache, sweating, flu-like symptoms. This could be a result of blood disorders that could lead to an increased risk of infections.
• Severe rash, which can lead to blistering and severe skin peeling.
• Unexplained muscle pain, tenderness or weakness. This could be a sign of rhabdomyolysis

Frequency not known (cannot be estimated from the available data)

• Signs and symptoms of a condition called “stress cardiomyopathy” which may include

chest pain, shortness of breath, dizziness, fainting, irregular heartbeat.
Other side effects that you should inform your doctor about include (the frequencies of these
side effects are included in the list below “Other side effects that may occur”):

• Cough, wheezing and difficulty breathing which may be accompanied by fever
• Black (tarry) stools or blood in the stools
• Itching, yellowing of the skin or eyes, dark urine, which may be symptoms of liver inflammation (hepatitis)
• Heart problems, such as fast or irregular heartbeat, increased blood pressure
• Eye problems, such as blurred vision, dilated pupils
• Nervous system problems, such as dizziness, tingling, movement disorders (muscle stiffness or spasms), convulsions
• Psychiatric problems, such as hyperactivity and feeling unusually excited
• Withdrawal symptoms (see section “How to take Zarelis, if you stop taking Zarelis”)
• Prolonged bleeding - if you cut or injure yourself, it may take longer than usual for the bleeding to stop.

Do not worry if you see a tablet in your stool after taking Zarelis. As the tablet
passes through the gastrointestinal tract, the venlafaxine is released slowly. The shape of the
tablet remains undissolved and is eliminated in the stool. Therefore, even if you see a
tablet in your stool, your dose of venlafaxine has been absorbed.
Other side effects that may occur

Very common (may affect more than 1 in 10 people)

• Dizziness; headache; drowsiness
• Insomnia
• Nausea; dry mouth, constipation
• Sweating (including night sweats)

Common (may affect up to 1 in 10 people)

• Decreased appetite
• Confusion; feeling detached (or estranged) from oneself; anorgasmia; decreased libido; agitation;
• Nervousness; abnormal dreams
• Tremor, a feeling of restlessness or inability to sit still or remain immobile. tingling; altered taste; increased muscle tone
• Visual disturbances, including blurred vision; dilated pupils; inability of the eye to focus on objects, from far to near
• Ringing in the ears (tinnitus)
• Increased heart rate; palpitations
• Increased blood pressure; hot flushes
• Shortness of breath; yawning
• Vomiting; diarrhea
• Moderate rashes; itching
• Increased frequency of urination; inability to urinate; difficulty urinating
• Menstrual irregularities such as increased bleeding, or increased irregular bleeding; Abnormal ejaculation/orgasm (in males); erectile dysfunction (impotence)
• Weakness (asthenia); fatigue; chills
• Weight gain; weight loss
• Increased cholesterol

Uncommon (may affect up to 1 in 100 people)

• Hyperactivity, racing thoughts and reduced need for sleep (mania)
• Hallucinations; feeling of detachment from reality; abnormal orgasm; absence of sensations or emotions; feeling of overstimulation; teeth grinding
• Fainting; involuntary muscle movements; impaired coordination and balance
• Feeling dizzy (especially when getting up too quickly); low blood pressure
• Vomiting blood, presence of tarry stools or blood in the stools, which may be a symptom of intestinal bleeding
• Sensitivity to sunlight; bruising; abnormal hair loss
• Inability to control urination
• Rigidity, spasms and involuntary movements of the muscles
• Small changes in blood levels of liver enzymes

Rare (may affect up to 1 in 1,000 people)

• Convulsions or seizures
• Cough, wheezing and shortness of breath which may be accompanied by fever
• Disorientation and confusion often accompanied by hallucinations (delirium)
• Excessive intake of water (known as SIADH)
• Decreased blood levels of sodium
• Intense eye pain and decreased or blurred vision
• Abnormal heartbeat, fast or irregular, which can lead to fainting
• Intense abdominal or back pain (which may indicate a serious problem with the intestine, liver or pancreas)
• Itching, yellowing of the skin and eyes, dark urine, or flu-like symptoms, which are symptoms of liver inflammation (hepatitis)

Very rare (may affect up to 1 in 10,000 people)

• Prolonged bleeding, which may lead to a reduction in platelets in the blood, leading to an increased risk of bruising or bleeding
• Abnormal secretion of breast milk
• Unexpected bleeding, such as bleeding gums, blood in the urine or vomit, or unexpected appearance of bruises or broken blood vessels (spider veins)

Frequency not known (cannot be estimated from the available data)

• Suicidal ideation and suicidal behaviors; cases of suicidal ideation and suicidal behaviors have been reported during therapy with venlafaxine or immediately after discontinuation of treatment (see section 2 “What you need to know before taking Zarelis”)
• Aggression
• Vertigo
• Abundant vaginal bleeding shortly after childbirth (postpartum hemorrhage), see section 2, Pregnancy and breastfeeding, for further information.

Sometimes Zarelis causes side effects that you may not notice, such as increases in blood
pressure or abnormal heartbeat; slight changes in blood levels of liver enzymes, sodium or
cholesterol. Less frequently, Zarelis can reduce the function of platelets in your blood,
leading to an increased risk of bruising and bleeding. Therefore, on certain occasions your
doctor may want to have blood tests, especially if you have been taking Zarelis for a long time.
If you experience any side effect, tell your doctor or pharmacist. This includes

Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any side effects not listed
in this leaflet. You can also report side effects directly through the national reporting system at
https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse . By reporting side effects you can help
provide more information on the safety of this medicine.

7. How to store Zarelis

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 packaging after the word
EXP. The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
Store in the original packaging to protect the medicine from moisture.
Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

8. Package contents and other information

What Zarelis contains
The active ingredient is venlafaxine.
Each Zarelis prolonged-release tablet contains 300 mg of venlafaxine (as hydrochloride).
The other ingredients are:
Mannitol (E421), Povidone, Macrogol, Microcrystalline cellulose, Anhydrous colloidal silica,
Magnesium stearate, Cellulose acetate, Hypromellose, Lactose monohydrate, Titanium dioxide (E171)
and Triacetin.

Description of the appearance of Zarelis and package contents
300 mg prolonged-release tablet: round, biconvex, white
Zarelis is available in blisters of 10, 14, 20, 28, 30, 42 50, 56, 60, 98, 100 and 500 prolonged-release tablets
Not all pack sizes may be marketed

Marketing Authorisation Holder
Italfarmaco S.p.A.
Viale F. Testi, 330, 20126 - Milan
Tel: +39.02.64431
Fax: +39.02.644346
e-mail: [email protected]

Manufacturer:
Laboratorios LICONSA, S.A.
Avda. Miralcampo, Nº 7, Polígono Industrial Miralcampo
19200 Azuqueca de Henares (Guadalajara), SPAIN

This medicinal product is authorised in the Member States of the EEA under the following names:
Sweden: Venlafaxin 1A Farma 300mg depot tablet
Estonia: Venlafaxine Liconsa
UK: Venlalic XL 300 mg prolonged-release tablets
Greece: Serosmine prolonged-release tablet 300 mg /TAB
Italy: Zarelis Netherlands: Venlafaxine Liconsa 300mg tablets with prolonged release
Portugal: Zarelix 300mg prolonged-release tablets