Package leaflet: Information for the user

Zarelis 37.5 mg Prolonged-release tablet, 75 mg Prolonged-release tablet, 150 mg Prolonged-release tablet, 225 mg Prolonged-release tablet

Venlafaxine
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 questions, ask your doctor or pharmacist.
This medicine has been prescribed for you only. Never give it to other people, even if their symptoms are the same as yours, because it may be harmful.
If you experience any side effects, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet:

What Zarelis is and what it is used for
What you need to know before taking Zarelis
How to take Zarelis
Possible side effects
How to store Zarelis
Contents of the pack and other information

1. What Zarelis is and what it is used for

Zarelis contains the active substance venlafaxine.
Zarelis is an antidepressant belonging to a group of medicines called serotonin and noradrenaline reuptake inhibitors (SNRIs). This group of medicines is used to treat 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 exact way antidepressants work is not fully understood; however, they may help by increasing the levels of serotonin and noradrenaline in the brain.
Zarelis is a treatment for adults with 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 left untreated, your condition may not resolve and may become worse 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 to any of the other ingredients of this medicine (listed in section 6).
if you are currently taking or have taken within the last 14 days any medicines known as irreversible monoamine oxidase inhibitors (MAOIs), used to treat depression or Parkinson’s disease. Taking an irreversible MAOI together with Zarelis may result in serious, even life-threatening, side effects. In addition, you must wait at least 7 days after stopping treatment with Zarelis before starting any irreversible MAOI (also see the section titled “Other medicines and Zarelis” and the information in that section regarding “Serotonin syndrome”).

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

If you are taking other medicines that, when taken together with Zarelis, may increase the risk of developing serotonin syndrome (see section “Other medicines and Zarelis”).
If you have swallowing difficulties, or stomach or intestinal disorders that reduce your ability to swallow or move food through the digestive tract normally.
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 (hyponatraemia).
If you tend to bruise easily or have a tendency to bleed easily (bleeding disorders), if you are taking 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 or someone in your family has had mania or bipolar disorder (feelings of over-excitement or euphoria).
If you have a history of aggressive behaviour.
Zarelis may cause a feeling of restlessness or inability to sit still during the first few weeks of treatment. If you experience these symptoms, inform 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 about harming yourself or committing suicide. These thoughts may increase when you first start taking antidepressants, as it takes time before these medicines begin to work—usually about two weeks, but sometimes longer. These thoughts may also occur when the dose is reduced or during discontinuation of treatment with Zarelis. You are more likely to have such thoughts:
- If you have previously had thoughts of suicide or self-harm.
- If you are young. Clinical studies have shown an increased risk of suicidal behaviour in young people (under 25 years) with psychiatric disorders who were 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 close relative or friend that you are depressed or have an anxiety disorder, and ask them to read this leaflet. You may ask them to inform you if they think your depression or anxiety is worsening, or if they 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 dental caries. Therefore, you should pay particular attention to your oral hygiene.

Diabetes
Blood glucose levels may be affected by the use of Zarelis. Therefore, the dosage of your diabetes medication may need to be adjusted.

Sexual dysfunction
Medicines such as Zarelis (so-called selective serotonin and noradrenaline reuptake inhibitors, SNRIs, or selective serotonin reuptake inhibitors, SSRIs) may cause symptoms of sexual dysfunction (see section 4). In some cases, these symptoms have persisted after discontinuation of treatment.

Children and adolescents
Zarelis is generally not intended for use in children and adolescents under 18 years of age.
Furthermore, you should know that patients under 18 years of age have a higher risk of experiencing adverse effects such as suicide attempts, suicidal thoughts, and hostility (mainly aggression, oppositional behaviour, and anger) when taking this type of medicine. Nevertheless, your doctor may prescribe this medicine to patients under 18 years of age if they consider it to be in the patient’s best interest. If your doctor has prescribed this medicine to a patient under 18 years of age and you wish to discuss it, please speak with your doctor. You must inform your doctor if any of the symptoms listed above appear or worsen while a patient under 18 years of age is taking Zarelis. In addition, the long-term effects of this medicine on growth, maturation, and mental and behavioural development in this age group have not been established.

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

Your doctor will decide whether you can take Zarelis together with other medicines.
Do not start or stop taking any other medicines—including over-the-counter medicines and herbal or natural remedies—without first consulting your doctor or pharmacist.

MAO inhibitors used to treat depression or Parkinson’s disease must not be taken with Zarelis. Inform your doctor if you have taken any of these medicines within the last 14 days (MAOIs: see section “What you need to know before taking Zarelis”).
Serotonin syndrome: A potentially life-threatening condition or reactions resembling Neuroleptic Malignant Syndrome (see section “Possible side effects”) may occur during treatment with venlafaxine, especially when taken together with other medicines. Examples of such medicines include:
- Triptans (used for migraine)
- Other medicines for depression, for example serotonin and noradrenaline reuptake inhibitors (SNRIs, SSRIs), tricyclic antidepressants, or medicines containing lithium
- Medicines containing amphetamines (used to treat 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, meperidine (pethidine), or pentazocine (used for severe pain)
- Medicines containing dextromethorphan (used to treat cough)
- Medicines containing methadone (used to treat opioid dependence or severe pain)
- Medicines containing methylene blue (used to treat high levels of methaemoglobin in the blood)
- Herbal preparations containing St. John’s wort (also known as Hypericum perforatum, a herbal remedy used to treat mild depression)
- Products containing tryptophan (used for sleep disorders and depression)
- Antipsychotics (used to treat symptoms such as hearing, seeing, or sensing things that are not there, having false beliefs, abnormal mistrust, unusual suspiciousness, confused thinking, or withdrawal)

Contact your doctor immediately or go to the nearest hospital emergency department if you think you may be experiencing serotonin syndrome.

You must inform your doctor if you are taking medicines that may affect heart rhythm.
Examples of such 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 interact with Zarelis and should be used with caution. It is particularly important that you inform your doctor or pharmacist if you are taking medicines containing:

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

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

Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, are planning to become pregnant, or are breastfeeding, consult your doctor or pharmacist before using this medicine.
You should use Zarelis only after discussing with your doctor the potential benefits and possible risks to the fetus.

Make sure your midwife and/or doctor knows that you are taking Zarelis. Medicines similar to Zarelis (SSRIs), if taken during pregnancy, may increase the risk of a serious condition in newborns called persistent pulmonary hypertension of the newborn (PPHN), which causes rapid breathing and a bluish skin colour in the baby. These symptoms usually occur within the first 24 hours after birth. If this happens to your baby, contact your midwife and/or doctor immediately.

If you take Zarelis during pregnancy, your baby may have breathing difficulties and feeding problems at birth. If you are concerned that your baby may be showing these symptoms at birth, contact your doctor and/or midwife, who will be able to assist you.

If you take Zarelis near the end of pregnancy, there may be an increased risk of heavy vaginal bleeding shortly after delivery, especially if you have bleeding disorders (a tendency to bleed easily). Inform your doctor or midwife 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 the medicine affecting the breastfed infant. Therefore, you should discuss this with your doctor, who will decide whether you should stop breastfeeding or stop treatment with this medicine.

Driving and using machines
Do not drive or operate tools or machinery until you know how this medicine affects you.

Zarelis contains lactose
This medicine contains lactose. If your doctor has diagnosed you with an intolerance to certain sugars, contact them before taking this medicine.

3. How to take Zarelis

Take this medicine exactly as prescribed by your doctor. If you have any doubts, consult your doctor or pharmacist.

The usual recommended starting dose for the treatment of depression, 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 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 it. The maximum dose for generalized anxiety disorder, social anxiety disorder, and panic disorder is 225 mg per day.

Take Zarelis at approximately the same time each day, either in the morning or in the evening. The tablets must be swallowed whole with liquid and must not be opened, broken, chewed, or dissolved.
You must take Zarelis with food.

If you have liver or kidney problems, discuss this with your doctor, as a dose adjustment of this medicine may be necessary.

Do not stop treatment with this medicine 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.

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 it is almost time for your next dose, skip the missed dose and take the next dose at the usual time. Do not take a double dose to make up for the forgotten dose.
Do not take more than the prescribed daily amount of Zarelis in a single day.

If you stop taking Zarelis
Do not stop treatment or reduce the dose without consulting your doctor, even if you feel better. If your doctor considers that you no longer need Zarelis, they may ask you to gradually reduce the dose before stopping treatment completely. It is known that adverse effects may occur when patients discontinue treatment with this medicine, especially if it is stopped abruptly or if the dose is reduced too quickly. Some patients may experience symptoms such as fatigue, dizziness, mental confusion, headache, insomnia, nightmares, dry mouth, loss of appetite, nausea, diarrhea, nervousness, agitation, confusion, tinnitus (ringing in the ears), tingling sensations, or rarely electric shock-like sensations, weakness, sweating, seizures, or flu-like symptoms, visual disturbances, and increased blood pressure (which may cause headache, dizziness, ringing in the ears, sweating, etc.).

Your doctor will advise you on how to gradually stop treatment with Zarelis. This may require a period of several weeks or months. In some patients, treatment may need to be discontinued very gradually over a period of months or longer.

If you experience any of these or other bothersome symptoms, consult your doctor for further advice.

If you have any doubts about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
If you experience any of the effects listed below, do not take any more Zarelis. Contact your doctor immediately or go to the nearest hospital emergency department.

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 patches on the skin that often itch)
Signs and symptoms of serotonin syndrome, which may include restlessness, hallucinations, loss of coordination, increased heart rate, elevated body temperature, rapid changes in blood pressure, overactive reflexes, diarrhea, coma, nausea, vomiting. In its most severe form, serotonin syndrome may present as Neuroleptic Malignant Syndrome (NMS). Signs and symptoms of NMS may include fever, increased heart rate, sweating, severe muscle rigidity, confusion, and increased muscle enzymes (detected via a blood test).
Signs of infection, such as high body temperature, chills, trembling, headache, sweating, flu-like symptoms. This could be due to blood disorders that may increase the risk of infections.
Severe skin rash, which may lead to blistering and serious peeling of the skin.
Unexplained pain, tenderness, or muscle 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” (also known as Takotsubo cardiomyopathy), which may include chest pain, shortness of breath, dizziness, fainting, irregular heartbeat.

Other side effects that you should report to your doctor include (the frequencies of these side effects are included in the list below “Other possible side effects”):

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 rapid 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), seizures
Psychiatric problems, such as hyperactivity and feeling unusually overexcited
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 alarmed if you see a tablet in your stool after taking Zarelis. As the tablet passes through the gastrointestinal tract, venlafaxine is slowly released. The tablet shell remains undissolved and is excreted in the stool. Therefore, even though you may see a tablet in your stool, the dose of venlafaxine has been absorbed.

Other possible side effects

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 from oneself; absence of orgasm; decreased libido; agitation; nervousness; abnormal dreams
Tremor, a feeling of restlessness or inability to sit still or remain motionless, tingling, altered taste, increased muscle tone
Vision disturbances, including blurred vision; dilated pupils; inability of the eye to focus 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 needing 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 detached from reality; abnormal orgasm; absence of sensations or emotions; feeling overexcited; teeth grinding
Fainting; involuntary muscle movements; impaired coordination and balance
Dizziness (especially when standing up too quickly); low blood pressure
Vomiting blood, black tarry stools, or blood in the stool, which may indicate gastrointestinal bleeding
Sensitivity to sunlight; bruising; abnormal hair loss
Inability to control urination
Muscle stiffness, spasms, and involuntary movements
Minor changes in blood levels of liver enzymes

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

Seizures or epileptic fits
Cough, wheezing, shortness of breath, which may be accompanied by fever
Disorientation and confusion, often accompanied by hallucinations (delirium)
Excessive water intake (known as SIADH)
Decreased blood sodium levels
Severe eye pain and reduced or blurred vision
Abnormal, rapid, or irregular heartbeat, which may lead to fainting
Severe abdominal or back pain (which may indicate a serious problem with the intestine, liver, or pancreas)
Itching, yellowing of the skin or eyes, dark urine, or flu-like symptoms, which are signs 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, increasing the risk of bruising or bleeding
Abnormal milk secretion (galactorrhea)
Unexpected bleeding, for example bleeding gums, blood in urine or vomit, or unexpected appearance of bruises or broken blood vessels (telangiectasia)

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

Suicidal thoughts and suicidal behaviour; cases of suicidal thoughts and behaviour have been reported during treatment with venlafaxine or shortly after stopping treatment (see section 2 “What you need to know before taking Zarelis”)
Aggression
Dizziness
Heavy vaginal bleeding shortly after childbirth (postpartum haemorrhage); see section 2, Pregnancy and breastfeeding, for further information.

Sometimes Zarelis may cause side effects that you may not notice, such as increases in blood pressure or abnormal heartbeat; minor changes in blood levels of liver enzymes, sodium, or cholesterol. Rarely, Zarelis may reduce the function of platelets in your blood, increasing the risk of bruising and bleeding. Therefore, your doctor may occasionally want to perform 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 any side effect not listed in this leaflet.

Reporting of side effects

If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. Reporting side effects can help provide more information on 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 stated on the pack. The expiry date refers to the last
day of that month.
This medicine does not require any special 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 via 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 substance is venlafaxine.
Each prolonged-release tablet of Zarelis 37.5, 75, 150 or 225 mg contains venlafaxine hydrochloride equivalent to 37.5 mg, 75 mg, 150 mg or 225 mg of venlafaxine.
The other components 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 (a mixture of hypromellose, monohydrate lactose, titanium dioxide (E171) and triacetin).

Description of the appearance of Zarelis and contents of the pack
37.5 mg prolonged-release tablets: white, round, biconvex tablets with a diameter of 7 mm
75 mg prolonged-release tablets: white, round, biconvex tablets with a diameter of 7.5 mm
150 mg prolonged-release tablets: white, round, biconvex tablets with a diameter of 9.5 mm
225 mg prolonged-release tablets: white, round, biconvex tablets with a diameter of 11 mm

Zarelis is available in blisters containing 10, 14, 20, 28, 30, 50, 56, 60, 100 and 500 tablets; and in plastic bottles containing 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 EEA Member States under the following names:
Sweden: Venlafaxin 1A Farma 37.5/75/150/225 mg depottabletter
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 comprimé à libération prolongée
Italy: Zarelis 37.5/75/150/225 mg Compressa a rilascio prolungato
Netherlands: Venlafaxine Liconsa 37.5/75/150 mg Tablet met verlengde afgifte
Venlafaxine Aurobindo 225 mg, Tablet met verlengde afgifte
Poland: Axyven
Portugal: Zarelix 37.5/75/150/225 mg comprimidos de libertação prolongada
UK: Venlalic XL 37.5/75/150/225 mg prolonged-release tablets

Patient Information Leaflet: Information for the user

Zarelis 300 mg Prolonged-Release Tablet

Venlafaxine
Please read 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 questions, ask your doctor or pharmacist.
This medicine has been prescribed for you only. Never give it to other people, even if their symptoms are the same as yours, because it could be dangerous.
If any adverse reaction occurs, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet:

What Zarelis is and what it is used for
What you need to know before taking Zarelis
How to take Zarelis
Possible side effects
How to store Zarelis
Contents of the pack and other information

3. What Zarelis is and what it is used for

Zarelis contains the active substance venlafaxine, which is an antidepressant belonging to a group of medicines called serotonin and noradrenaline reuptake inhibitors (SNRIs).
This group of medicines is used to treat 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 exact way antidepressants work is not fully understood, but they may help by increasing the levels of serotonin and noradrenaline in the brain.
Zarelis is a treatment for depression in adults. Appropriate treatment of depression is important to help you feel better. If left untreated, your condition may not improve and may become more severe and more difficult to treat.

4. What you should know before taking Zarelis

Do not take Zarelis

if you are allergic to venlafaxine or to any of the other ingredients of this medicine (listed in section 6).
if you are currently taking or have taken within the last 14 days any medicines known as irreversible monoamine oxidase inhibitors (I-MAO), used to treat depression or Parkinson’s disease. Taking an irreversible I-MAO together with Zarelis may cause serious, even life-threatening, side effects. In addition, you must wait at least 7 days after stopping treatment with venlafaxine before starting any irreversible I-MAO (also see the section titled “Other medicines and Zarelis” and the information contained therein regarding “Serotonin syndrome”).

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

If you are using other medicines that, when taken together with Zarelis, may increase the risk of developing serotonin syndrome (see section “Other medicines and Zarelis”)
If you have swallowing difficulties or stomach or intestinal problems that reduce your ability to swallow or pass food through the digestive tract normally
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 (hyponatraemia)
If you have a tendency to bruise easily or a tendency to bleed easily (bleeding disorders), if you are taking other medicines that may increase the risk of bleeding, e.g. warfarin (used to prevent thrombosis), or if you are pregnant (see “Pregnancy and Breast-feeding”)
If you have a history, or if someone in your family has had a history, of mania or bipolar disorder (feelings of over-excitement or euphoria)
If you have a history of aggressive behaviour. Zarelis may cause a feeling of restlessness or inability to sit still during the first few weeks of treatment. If you experience these symptoms, inform your doctor.

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

If you have previously had thoughts of suicide or of harming yourself.
If you are young. Data from clinical studies have shown an increased risk of suicidal behaviour in young people (under 25 years of age) with psychiatric disorders who were treated with an antidepressant.

If at any time you have thoughts of harming yourself or of suicide, contact your doctor or go to the hospital immediately.
It may help to tell a close relative or friend that you are depressed and ask them to read this leaflet. You may ask them to let you know if they think your depression is getting worse or if they 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 dental caries. You should therefore pay particular attention to your oral hygiene.

Diabetes
Blood glucose levels may be altered by the use of Zarelis. Therefore, the dosage of your diabetes medications may need to be adjusted.

Sexual dysfunction
Medicines such as Zarelis (so-called selective serotonin reuptake inhibitors SSRIs and serotonin-noradrenaline reuptake inhibitors SNRIs) may 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 recommended for use in children and adolescents under 18 years of age.
Furthermore, you should know that patients under 18 years of age have a higher risk of adverse reactions such as suicide attempts, suicidal thoughts and hostility (mainly aggression, oppositional behaviour and anger) when taking this type of medicine. Nevertheless, your doctor may prescribe this medicine for patients under 18 years of age if they consider it to be in the patient’s best interest. If your doctor has prescribed this medicine for a patient under 18 years of age and you wish to discuss it, please speak to your doctor. You must inform your doctor if any of the symptoms listed above appear or worsen while a patient under 18 years of age is taking venlafaxine. In addition, the long-term effects of this medicine on growth, maturation, and mental and behavioural development in this age group have not been established.

Other medicines and Zarelis
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.
Your doctor will decide whether you can use Zarelis with other medicines.
Do not start or stop treatment with other medicines, including over-the-counter medicines and herbal or natural remedies, without first consulting your doctor or pharmacist.

Monoamine oxidase inhibitors used to treat depression or Parkinson’s disease must not be taken with venlafaxine. Inform your doctor if you have taken these medicines within the last 14 days (I-MAOs: see section “What you should know before taking Zarelis”).
Serotonin syndrome: A potentially life-threatening condition or reactions resembling Neuroleptic Malignant Syndrome (see section “Possible side effects”) may occur during treatment with venlafaxine, particularly when taken together with other medicines. Examples of such medicines include:
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 to treat attention deficit hyperactivity disorder (ADHD), narcolepsy and obesity)
Medicines containing linezolid, an antibiotic (used to treat infections)
Medicines containing moclobemide, an I-MAO (used to treat depression)
Medicines containing sibutramine (used for weight loss)
Medicines containing tramadol, fentanyl, tapentadol, meperidine, or pentazocine (used to treat severe pain)
Medicines containing dextromethorphan (used to treat cough)
Medicines containing methadone (used to treat opioid dependence or severe pain)
Medicines containing methylene blue (used to treat high levels of methaemoglobin in the blood)
Herbal preparations containing St. John’s wort (also known as Hypericum perforatum, a herbal remedy used to treat mild depression)
Products containing tryptophan (used for sleep disorders and depression)
Antipsychotics (used to treat symptoms such as hearing, seeing or sensing things that are not there, having false beliefs, abnormal distrust, unusual suspiciousness or confused thinking, or withdrawal)

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 may present as neuroleptic malignant syndrome (NMS). Signs and symptoms of NMS may include fever, rapid heartbeat, sweating, severe muscle rigidity, confusion and increased muscle enzymes (detected through a blood test).
Inform your doctor immediately, or go to the nearest hospital emergency department if
you think you may have serotonin syndrome.
You must inform your doctor if you are taking medicines that can affect heart rhythm.
Examples of such 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 interact with Zarelis and should be used with caution. It is particularly important that you inform your doctor or pharmacist if you are taking medicines containing:

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

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

Pregnancy and breast-feeding
If you are pregnant, think you may be pregnant, planning to become pregnant or breast-feeding, consult your doctor or pharmacist before using this medicine.
You should use Zarelis only after discussing with your doctor the potential benefits and potential risks to the fetus.
Ensure that your midwife and/or doctor knows that you are taking Zarelis. Similar medicines (SSRIs) taken during pregnancy may increase the risk of a serious condition in newborns called persistent pulmonary hypertension of the newborn (PPHN), which causes rapid breathing and a bluish skin colour in the baby. These symptoms usually occur within the first 24 hours after birth. If this happens to your baby, contact your midwife and/or doctor immediately.
If you are taking Zarelis during pregnancy, your baby may have breathing difficulties and feeding problems at birth. If you are concerned that your baby may be showing these symptoms at birth, contact your doctor and/or midwife, who will be able to assist you.
If you take Zarelis near the end of your pregnancy, there may be an increased risk of heavy bleeding shortly after delivery, especially if you have bleeding disorders (a tendency to bleed easily). Inform your doctor or midwife 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 the medicine affecting the breastfed infant. Therefore, you must discuss this with your doctor, who will decide whether you should discontinue breast-feeding or stop treatment with this medicine.

Driving and using machines
Do not drive and do not operate tools or machinery until you know how this medicine affects you.

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

3. How to take Zarelis

Take this medicine exactly as directed by your doctor. If you have any doubts, consult your doctor or pharmacist.
The usual recommended starting dose for the treatment of depression 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.
Take Zarelis at approximately the same time each day, either in the morning or in the evening. The tablet must be swallowed whole with liquid and must not be broken, chewed or dissolved.
You must take Zarelis with food.
If you have liver or kidney problems, discuss this with your doctor, as a dose adjustment of venlafaxine may be necessary.
Do not stop treatment with Zarelis without consulting your doctor (see the 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.
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 it is almost time for your next dose when you remember, skip the missed dose and take the next dose at the usual time. Do not take a double dose to make up for a forgotten dose.
Do not take more Zarelis in one day than the amount prescribed for that day.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
If you experience any of the side effects listed below, do not take any more Zarelis. Contact your doctor immediately or go to the nearest hospital emergency department.

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 skin rash, itching, hives (raised red or pale patches on the skin which often itch)
Signs and symptoms of serotonin syndrome, which may include restlessness, hallucinations, loss of coordination, rapid heartbeat, increased body temperature, rapid changes in blood pressure, overactive reflexes, diarrhoea, coma, nausea, vomiting. In its most severe form, serotonin syndrome may present as Neuroleptic Malignant Syndrome (NMS). Signs and symptoms of NMS may include fever, rapid heartbeat, sweating, severe muscle rigidity, confusion, and increased muscle enzymes (detected through a blood test).
Signs of infection, such as high body temperature, chills, shaking, headache, sweating, flu-like symptoms. This could be due to blood disorders that may lead to an increased risk of infections.
Severe skin rash, which may lead to blistering and serious peeling of the skin.
Unexplained pain, tenderness or muscle 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 report to your doctor include (the frequencies of these side effects are included in the list below “Other possible side effects”):

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 rapid 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), seizures
Psychiatric problems, such as hyperactivity and feeling unusually excited
Withdrawal symptoms (see section “How to take Zarelis, if you stop treatment with Zarelis”)
Prolonged bleeding – if you cut or injure yourself, it may take longer than usual for the bleeding to stop.

Do not be alarmed if you see a tablet in your stools after taking Zarelis. As the tablet passes through the gastrointestinal tract, venlafaxine is slowly released. The tablet shell remains undissolved and is eliminated in the stools. Therefore, even if you see a tablet in your stools, your dose of venlafaxine has been absorbed.

Other possible side effects
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 separated) from oneself; absence of orgasm; decreased libido; agitation
Nervousness; abnormal dreams
Tremor, a feeling of restlessness or inability to sit still, tingling; altered taste; increased muscle tone
Vision disturbances, including blurred vision; dilated pupils; inability of the eye to focus from far to near objects
Ringing in the ears (tinnitus)
Fast heartbeat; palpitations
Increased blood pressure; hot flushes
Shortness of breath; yawning
Vomiting; diarrhoea
Moderate skin rashes; itching
Increased frequency of needing 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 detached from reality; abnormal orgasm; absence of sensations or emotions; feeling overexcited; teeth grinding
Fainting; involuntary muscle movements; altered coordination and balance
Dizziness (especially when standing up too quickly); low blood pressure
Vomiting blood, black tarry stools or blood in stools, which may be a sign of intestinal bleeding
Sensitivity to sunlight; bruising; abnormal hair loss
Inability to control urination
Muscle stiffness, spasms and involuntary movements
Minor changes in blood levels of liver enzymes

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

Seizures or epileptic fits
Cough, wheezing and shortness of breath which may be accompanied by fever
Disorientation and confusion often accompanied by hallucinations (delirium)
Excessive water intake (known as SIADH)
Decreased blood sodium levels
Severe eye pain and reduced or blurred vision
Abnormal, rapid or irregular heartbeat, which may lead to fainting
Severe 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, resulting in an increased risk of bruising or bleeding
Abnormal milk secretion (galactorrhea)
Unexpected bleeding, for example bleeding gums, blood in urine or vomit, or unexpected appearance of bruises or broken blood vessels (telangiectasia)

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

Suicidal thoughts and suicidal behaviour; cases of suicidal thoughts and suicidal behaviour have been reported during treatment with venlafaxine or immediately after stopping treatment (see section 2 “What you should know before taking Zarelis”)
Aggression
Dizziness
Heavy vaginal bleeding shortly after childbirth (postpartum haemorrhage); 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; minor changes in blood levels of liver enzymes, sodium or cholesterol. More rarely, Zarelis may reduce the function of platelets in your blood, leading to an increased risk of bruising and bleeding. Therefore, your doctor may occasionally wish to carry out blood tests, particularly if you have been taking Zarelis for a long time.

If you experience any side effect, tell your doctor or pharmacist. This includes any side effect not listed in this leaflet.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via 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 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 via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

8. Contents of the pack and other information

What Zarelis contains
The active substance is venlafaxine.
Each prolonged-release tablet of Zarelis contains 300 mg of venlafaxine (as hydrochloride).
The other components 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 contents of the pack
300 mg prolonged-release tablet: round, biconvex, white
Zarelis is available in blisters containing 10, 14, 20, 28, 30, 42, 50, 56, 60, 98, 100 and 500
prolonged-release tablets.
Not all pack sizes may be marketed.

Marketing Authorization Holder
Italfarmaco S.p.A.
Viale F. Testi, 330, 20126 - Milan, Italy
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 authorized in EEA Member States under the following names:
Sweden: Venlafaxin 1A Farma 300mg depottabletter
Estonia: Venlafaxine Liconsa
UK: Venlalic XL 300 mg prolonged-release tablets
Greece: Serosmine Δισκίο παρατεταμένης αποδέσμευσης 300 mg /TAB
Italy: Zarelis
Netherlands: Venlafaxine Liconsa 300mg tabletten met verlengde afgifte
Portugal: Zarelix 300mg comprimidos de libertação prolongada