Package Insert: Information for the User

ZARELIS Retard 225 mg prolonged-release tablets

venlafaxine

Read this package insert carefully before you start taking this medicine, because it contains important information for you

• Keep this package insert, as you may need to read it again.
• If you have any questions, consult your doctor or pharmacist.
• This medicine has been prescribed for you only and should not be given to others even if they have the same symptoms as you, as it may harm them.
• If you experience any side effects, consult your doctor or pharmacist, even if they are not listed in this package insert. See section 4.

6. Contents of the pack and additional information

Zarelis Retard contains the active substance venlafaxine.

Zarelis Retard is an antidepressant that belongs to a group of medications called serotonin and norepinephrine reuptake inhibitors (SNRIs). This group of medications is used to treat depression and other conditions such as anxiety disorders. The exact mechanism of action of antidepressants is not fully understood, but they may help increase levels of serotonin and norepinephrine in the brain.

Zarelis Retard is a treatment for adults with depression.Zarelis Retard is also a treatment for adults with the following anxiety disorders:generalized anxiety disorder,social anxiety disorder (fear or avoidance of social situations) andpanic disorder (panic attacks). Treating depressive and anxiety disorders properly is important to help you feel better. If left untreated, your condition may not go away or may worsen and become more difficult to treat.

Do not take Zarelis Retard

• If you are allergic to venlafaxine or any of the other ingredients of this medication (described in section 6).
• If you are also taking or have taken in the last 14 days, any medication known as an irreversible monoamine oxidase inhibitor (IMAO), used to treat depression or Parkinson's disease. Taking an IMAO irreversible with Zarelis Retard may produce severe or potentially life-threatening side effects. Additionally, you should wait at least 7 days after stopping Zarelis Retard before taking any IMAO irreversible (see also the section called “Other medications” and Zarelis Retard and the information in that section on “Serotonin syndrome”).

Warnings and precautions

Speak with your doctor or pharmacist before starting to take Zarelis Retard

• If you are using other medications that taken with Zarelis Retard may increase the risk of developing Serotonin syndrome (see the section “Other medications and Zarelis Retard ”).
• If you have a swallowing disorder, stomach or intestinal disorder that reduces your ability to swallow or pass food through normal intestinal movements.
• If you have eye problems, such as certain types of glaucoma (increased pressure in the eye).
• If you have a history of high blood pressure.
• If you have a history of heart problems.
• If you have an abnormal heart rhythm.
• If you have a history of seizures (convulsions).
• If you have a history of low sodium levels in the blood (hyponatremia).
• If you have a history of bleeding disorders (tendency to develop ecchymoses or tendency to bleed easily) or if you are using other medications that may increase the risk of bleeding, e.g., warfarin (used to prevent blood clots) or if you are pregnant (see section “Pregnancy and breastfeeding”).
• If you have a history of, or if someone in your family has had, mania or bipolar disorder (feeling overexcited or euphoric).
• If you have a history of aggressive behavior.

Zarelis Retard may cause a feeling of restlessness or difficulty sitting or staying still during the first weeks of treatment. You should consult your doctor if this occurs.

Do not drink alcohol during treatment with Zarelis Retard, as it may cause extreme fatigue and unconsciousness. Taking it with certain medications and/or alcohol may worsen the symptoms of depression and other conditions, such as anxiety disorders.

Thoughts of suicide and worsening of your depression or anxiety disorder

If you are depressed and/or have an anxiety disorder, you may sometimes have thoughts of harming yourself or committing suicide. These thoughts may increase when you start taking antidepressants, as all these medications take time to work, usually two weeks but sometimes longer. These thoughts may also occur when you reduce your dose or during the end of treatment with Zarelis Retard.

It is more likely to happen:

• If you have had previous thoughts of suicide or self-harm.
• If you are a young adult. Clinical trial information has shown an increased risk of suicidal behavior in young adults (less than 25 years old) with psychiatric disorders treated with antidepressants.

If you have thoughts of harming yourself or committing suicide at any time, contact your doctor or go to the hospital directly.

You may find it helpful to tell a close family member or friend that you are depressed or have an anxiety disorder, and ask them to read this leaflet. You can also ask them to tell you if they think your depression or anxiety is getting worse, or if they are concerned about changes in your behavior.

Dry mouth

Dry mouth has been reported in 10% of patients treated with venlafaxine. This may increase the risk of dental decay (caries). Therefore, you should take care with your dental hygiene.

Diabetes

Your blood glucose levels may be affected by Zarelis Retard. Therefore, you may need to adjust the dose of your diabetes medication.

Sexual problems

Some medications in the group to which Zarelis Retard belongs (called IRSN) may cause symptoms of sexual dysfunction (see section 4). In some cases, these symptoms persist after stopping treatment.

Children and adolescents

Zarelis Retard should not be used normally in the treatment of children and adolescents under 18 years old. Additionally, you should know that in patients under 18 years old, there is a higher risk of adverse effects such as suicidal thoughts, ideas of suicide, and hostility (predominantly aggression, confrontational behavior, and irritability) when taking this type of medication. However, the doctor who prescribes it may prescribe it to patients under 18 years old when they decide it is the best option for the patient. If the doctor who prescribes it has prescribed it to a patient under 18 years old and wants to discuss this decision, please return to your doctor. You should inform your doctor if any of the symptoms listed above develop or worsen in these patients under 18 years old who are taking Zarelis Retard. Additionally, the long-term effects of this medication on growth, maturation, and cognitive and behavioral development have not yet been demonstrated.

Other medications and Zarelis Retard

Inform your doctor or pharmacist if you are using, have used recently, or may use any other medication.

Your doctor should decide if you can take Zarelis Retard with other medications.

Do not start or stop taking any medication, including those sold without a prescription, natural remedies, and herbal products, before checking with your doctor or pharmacist.

• Irreversible monoamine oxidase inhibitors, used to treat depression and Parkinson's disease, should not be used with Zarelis Retard. Inform your doctor if you have taken these medications in the last 14 days (IMAO: see section “What you need to know before starting to take Zarelis Retard”).
• Serotonin syndrome:

Serotonin syndrome, a potentially life-threatening state, or Malignant Neuroleptic Syndrome (MNS) (see section “Possible side effects”), may occur with treatment with venlafaxine, particularly when taken with other medications.

Examples of these medications include:

• Triptans (used for migraines)
• Other medications for treating depression, such as ISRN, ISRS, tricyclic antidepressants, or medications containing lithium
• Medications containing amphetamines (used to treat attention deficit hyperactivity disorder (ADHD), narcolepsy, and obesity)
• Medications containing the antibiotic linezolid (used to treat infections)
• Medications containing moclobemide, an IMAO (used to treat depression)
• Medications containing sibutramine (used for weight loss)
• Medications containing opioids (e.g., buprenorphine, tramadol, fentanyl, tapentadol, pethidine, or pentazocine) (used to treat severe pain)
• Medications containing dextromethorphan (used to treat cough)
• Medications containing methadone (used to treat opioid addiction or severe pain)
• Medications containing methylene blue (used to treat elevated methemoglobin levels in the blood)
• Products containing St. John's Wort (also known as “Hypericum perforatum”, a natural remedy or herbal product used to treat mild depression)
• Products containing tryptophan (used for problems such as sleep and depression)
• Antipsychotics (used to treat a disorder with auditory, visual, or perceptual hallucinations, delusions, unusual distrust, confused thinking, and withdrawal symptoms)

The signs and symptoms of Serotonin syndrome may include a combination of the following: restlessness, hallucinations, loss of coordination, rapid heartbeat, increased body temperature, rapid changes in blood pressure, hyperactive reflexes, diarrhea, coma, nausea, and vomiting.

Serotonin syndrome, in its most severe form, may resemble Malignant Neuroleptic Syndrome (MNS). The symptoms and signs of MNS may include a combination of fever, rapid heart rate, sweating, severe muscle rigidity, confusion, and increased levels of muscle enzymes (determined in blood).

Inform your doctor immediately or go to the nearest hospital if you think you are experiencing Serotonin syndrome.

You should inform your doctor if you are taking medications that affect heart rate.

Examples of these medications include:

• Antiarrhythmics such as quinidine, amiodarone, sotalol, or dofetilide (used to treat heart rhythm disorders).
• Antipsychotics such as thioridazine (see also above the section “Serotonin syndrome”).
• Antibiotics such as erythromycin or moxifloxacin (used to treat bacterial infections).
• Antihistamines (used to treat allergies).

The following medications may also interact with Zarelis Retard and should be used with caution. It is especially important to mention to your doctor or pharmacist if you are taking medications that contain:

• Ketoconazole (antifungal medications).
• Haloperidol or risperidone (used to treat psychiatric disorders).
• Metoprolol (a beta-blocker used to treat high blood pressure and heart problems).

Use of Zarelis Retard with food, drinks, and alcohol

Zarelis Retard should be taken with food (see section 3 “How to take Zarelis Retard”).

Do not drink alcohol during treatment with Zarelis Retard. Taking it with alcohol may cause extreme fatigue and unconsciousness, and worsen the symptoms of depression and other conditions, such as anxiety disorders.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, or if you think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist before taking this medication. You should only take Zarelis Retard after discussing with your doctor the possible benefits and risks for the unborn baby.

Make sure your midwife and/or doctor know that you are using Zarelis Retard. When taking similar medications (called serotonin reuptake inhibitors: SSRIs) during pregnancy, there may be an increased risk of a serious condition called persistent pulmonary hypertension of the newborn (PPHN), causing the baby to breathe faster and appear blue. These symptoms usually start within the first 24 hours after birth. If this happens to you, you should contact a doctor and/or midwife immediately.

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

If you are taking this medication during pregnancy, other symptoms that your baby may have when born are feeding problems and breathing difficulties. If your baby has these symptoms when born and you are concerned, contact your doctor and/or midwife who can advise you.

Zarelis Retard passes into breast milk. There is a risk of an effect on the baby, so you should discuss the case with your doctor, and they will decide whether you should stop breastfeeding or stop taking this medication.

Driving and operating machinery

Do not drive or operate tools or machines until you know how Zarelis Retard affects you.

Zarelis Retard contains lactose

This medication contains lactose. If your doctor has told you that you have intolerance to certain sugars, consult with him before taking this medication.

Follow exactly the administration instructions of this medication as indicated by your doctor or pharmacist. In case of doubt, consult your doctor or pharmacist again.consulte de nuevo a su médico o farmacéutico.

The usual initial dose recommended for the treatment of depression, generalized anxiety disorder, and social anxiety disorder is 75 mg per day. Your doctor may increase the dose gradually and, if necessary, raise it 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 increase it gradually. The maximum dose for generalized anxiety disorder, social anxiety disorder, and panic disorder is 225 mg/day.

Take Zarelis Retard approximately at the same time every day, either in the morning or at night. The tablets should be swallowed whole with liquids and should not be opened, crushed, chewed, or dissolved.

Zarelis Retard should be taken with food.

If you have liver or kidney problems, talk to your doctor as your dose of this medication may be different.

Do not stop taking Zarelis Retard without consulting your doctor (see section “If you interrupt treatment with Zarelis Retard”).

If you take more Zarelis Retard than you should

Immediately contact your doctor or pharmacist if you take more medication than prescribed by your doctor. You can also contact the Toxicological Information Service, phone 91 562 04 20, indicating the medication and the amount taken.

A overdose can put your life in danger, especially with the simultaneous taking of certain medications and/or alcohol (see Taking Zarelis Retard with other medications).

The symptoms of a possible overdose may include palpitations, changes in alertness (ranging from drowsiness to coma), blurred vision, seizures or attacks, and vomiting.

If you forgot to take Zarelis Retard

If you have not taken a dose, take it as soon as you remember. However, if it is already time for your next dose, skip the missed dose and take only one dose as usual. Do not take a double dose to compensate for a missed dose. Do not take more than the daily dose of Zarelis Retard prescribed in a day.

If you interrupt treatment with Zarelis Retard

Do not stop taking your treatment or reduce the dose without consulting your doctor, even if you feel better. If your doctor thinks you no longer need Zarelis Retard, they may ask you to reduce the dose gradually before stopping treatment completely. It is known that adverse effects occur when people stop using this medication, especially when it is stopped suddenly or if the dose is reduced very quickly. Some patients may experience symptoms such as suicidal thoughts, aggression, fatigue, dizziness, instability, headaches, insomnia, nightmares, dry mouth, loss of appetite, nausea, diarrhea, nervousness, agitation, confusion, ringing in the ears, tingling, or, in rare cases, electrical discharge sensations, weakness, sweating, seizures, or symptoms similar to the flu, vision problems, and increased blood pressure (which can cause headaches, dizziness, ringing in the ears, sweating, etc.).

Your doctor will advise you on how to gradually stop treatment with Zarelis Retard. This may take several weeks or months. In some patients, the interruption may need to be very gradual over periods of several 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 other questions about the use of this medication, ask your doctor or pharmacist.

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

If any of the following effects occur, do not take more Zarelis Retard. Inform your doctor immediately, or go to the nearest hospital emergency room:

Rare (may affect up to 1 in 100 people)

• Swelling of the face, mouth, tongue, throat, hands, or feet, and/or itchy, swollen, and blistered skin, 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, or urticaria (raised, red, or pale areas of skin that often itch).
• The symptoms and signs of serotonin syndrome may include hyperactivity, hallucinations, lack of coordination, rapid heart rate, increased body temperature, rapid changes in blood pressure, hyperactive reflexes, diarrhea, coma, nausea, and vomiting.

Serotonin syndrome, in its most severe form, may resemble Malignant Neuroleptic Syndrome (MNS). The symptoms and signs of MNS may include a combination of fever, rapid heart rate, sweating, severe muscle rigidity, confusion, and increased levels of muscle enzymes (determined by blood tests).

• Symptoms of infection, such as fever, chills, shivering, headache, sweating, or symptoms similar to the flu. This may be due to a blood disorder that can increase the risk of infection.
• Severe rash, which may lead to the formation of severe blisters and skin peeling.
• Unexplained muscle pain, discomfort, or weakness. This may be a sign of rhabdomyolysis.

Unknown frequency (cannot be estimated from available data)

• Symptoms and signs of a condition called "stress cardiomyopathy" that may include chest pain, shortness of breath, dizziness, fainting, irregular heartbeats.

Other side effects that you should inform your doctor include(the frequency of these side effects are included in the lower list “other side effects that may occur”):

• Coughing, wheezing, and difficulty breathing that may be accompanied by an increased temperature.
• Stool that is black and tarry, or blood in the stool.
• Itching, yellow eyes or skin, dark urine, which are symptoms of liver inflammation (hepatitis).
• Heart problems, such as rapid or irregular heart rate, or high blood pressure.
• Eye problems, such as blurred vision, dilated pupils.
• Nervous system problems: dizziness, numbness, movement disorder(muscle spasms and rigidity), seizures, or attacks.
• Psychiatric problems, such as hyperactivity and euphoria (unusual overexcitement).
• Withdrawal effects from treatment (see section “How to takeZarelis Retard, If you interrupt treatment with Zarelis Retard”).
• Prolonged bleeding – If you cut or injure yourself, the bleeding may take a little longer to stop.
• Heavy vaginal bleeding shortly after delivery (postpartum hemorrhage), see “Pregnancy and breastfeeding” in section 2 for more information.

Do not worry if you see a tablet in your stool after taking this medicine. As the tablets pass through your gastrointestinal tract, the venlafaxine is slowly released. The tablet shape does not dissolve and is eliminated in the stool. Therefore, even if you see the tablet in the stool, the dose of the medicine has been absorbed.

Other side effects that may occur

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

• Dizziness, headaches,sleepiness.
• Insomnia.
• Nausea, dry mouth, constipation.
• Sweating (including night sweats).

Common (may affect up to 1 in 10 people)

• Loss of appetite.
• Confusion; feeling disconnected (or detached) from oneself, anorgasmia, decreased libido, agitation.
• Nervousness, abnormal dreams.
• Tremors, a feeling of restlessness or inability to sit or stay still, altered perception of taste,, increased muscle tone.
• Eye problems including blurred vision; dilated pupils, difficulty focusing from far to near.
• Ringling in the ears (tinnitus).
• Rapid heart rate, palpitations.
• Increased blood pressure; hot flashes.
• Difficulty breathing, yawning.
• Vomiting; diarrhea.
• Mild skin rash, itching.
• Increased frequency of urination, inability to urinate, difficulty urinating.
• Irregular menstrual periods, such as increased bleeding or irregular bleeding; abnormal ejaculation / orgasm (men); erectile dysfunction (impotence).
• Weakness (asthenia); fatigue; chills.
• Weight gain or loss.
• Increased cholesterol.

Rare (may affect up to 1 in 100 people)

• Hyperactivity, rapid thoughts, and decreased need for sleep (mania).
• Hallucinations; feeling disconnected (or detached) from reality; abnormal orgasm ; lack of feelings or emotions; overexcitement or euphoria; teeth grinding.
• Fainting, involuntary muscle movements, altered coordination and balance.
• Feeling dizzy (especially when standing up too quickly), decreased coordination and balance.
• Vomiting blood, stool that is black and tarry, or blood in the stool that may be a sign of internal bleeding.
• Sensitivity to sunlight, petechiae, rash.
• Inability to control urination.
• Rigidity, spasms, and involuntary muscle movements.Changes in liver enzyme levels.

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

• Seizures or attacks.
• Coughing, wheezing, and difficulty breathing that may be accompanied by a high temperature.
• Disorientation and confusion, often accompanied by hallucinations (delirium).
• Excessive water intake (known as SIADH).
• Decreased sodium levels in the blood.
• Severe eye pain and reduced or blurred vision.
• Abnormal heart rhythm, rapid or irregular heart rate, which may lead to fainting.
• Severe abdominal or back pain (which may indicate a serious problem in the intestine, liver, or pancreas).
• Itching, yellow eyes or skin, dark urine, symptoms similar to the flu, which are symptoms of liver inflammation (hepatitis).

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

• Prolonged bleeding, which may be due to a reduced number of platelets in the blood that leads to petechiae or bleeding.
• Abnormal milk production.
• Unexpected bleeding, such as bleeding gums, blood in urine or vomit, or the appearance of petechiae or vessel rupture (broken veins).

Unknown frequency (cannot be estimated from available data)

• Suicidal thoughts and behavior. Cases of suicidal thoughts and behavior have been reported during treatment with venlafaxine or shortly after discontinuation of treatment (see section 2, What you should know before starting to take Zarelis Retard).
• Aggression.
• Dizziness.
• Heavy vaginal bleeding shortly after delivery (postpartum hemorrhage), see “Pregnancy and breastfeeding” in section 2 for more information.

Zarelis Retardmay sometimes cause unwanted effects that you may not be aware of, such as increased blood pressure or abnormal heart rhythm; mild changes in liver enzyme levels, sodium, or cholesterol. Less frequently, Zarelis Retardmay reduce the function of platelets in the blood, which increases the risk of petechiae or bleeding. Therefore, your doctor may wish to perform occasional blood tests, particularly if you have been taking Zarelis Retard for a long time.

If you experience any of the side effects, inform your doctor or pharmacist. This includes any side effects not listed in this leaflet.

Reporting of side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through theSpanish System for the Pharmacovigilance of Medicines for Human Use:https://www.notificaram.es.By reporting side effects, you can contribute to providing more information on the safety of this medicine.

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

Do not usethis medication after the expiration date that appears on the packaging, after CAD. The expiration date is the last day of the month indicated.

This medication does not require any special storage temperature. Store in the original packaging to protect it from moisture.

Do not dispose of any medication through the drains or in the trash. Deposit the containers and medications you no longer need at the SIGRE collection pointof the pharmacy. If in doubt, ask your pharmacist how to dispose of the containers and medications you no longer need. In this way, you will help protect the environment.

Composition of Zarelis Retard

The active ingredient is venlafaxine.

Each tablet contains 225 mg of venlafaxine (as hydrochloride).

The other components are:

Core:mannitol (E421), povidone K-90, macrogol 400, microcrystalline cellulose, anhydrous colloidal silica, magnesium stearate.

Covering:cellulose acetate, macrogol 400, Opadry Y 30 18037 (a mixture of hypromellose, lactose monohydrate, titanium dioxide (E171), and triacetin).

Appearance of the product and contents of the package

Prolonged-release tablets 11 mm in diameter, round, biconvex, white.

Zarelis Retard 225 mg is available in blisters of10, 14, 20, 28, 30, 50, 56, 60, 70, 98, 100, and 500 tablets, and in plastic bottles of 10, 14, 20, 28, 30, 50, 56, 60, 100, and 500 tablets.

Only some package sizes may be marketed.

Marketing Authorization Holder:

ITALFARMACO, S.A.

San Rafael, 3 – 28108 Alcobendas (Madrid), SPAIN

Tel.: 916572323

Responsible for manufacturing:

Laboratorios LICONSA, S.A.

Avda.Miralcampo, Nº 7, Industrial Estate Miralcampo

19200 Azuqueca de Henares (Guadalajara), SPAIN

or

Sandoz A/S

Edvard Thomsens Vej 14
2300 København S,

Denmark

or

Genericon Pharma

Gesellschaft m.b.H.,

Hafnerstrasse 211, 8054 Graz,

Austria

This medicine is authorized in the member states of the European Economic Area with the following names:

Austria: Venlafaxin Genericon 225 mg, Retardtabletten

Sweden: Venlafaxine AGP 225 mg depottabletter

Spain: Zarelis Retard 225 mg prolonged-release tablets

Germany:Venlafaxin AAA-Pharma 225 mg Retardtabletten

Finland: Subelan 225 mg depottabletti

Belgium:Sybexlan 225 mg tablets with prolonged release / comprimés à libération prolongée/ Retardtabletten

Luxembourg: Sybexlan 225 mg tablets with prolonged release / comprimés à libération prolongée/ Retardtabletten

Last review date of this leaflet:June 2023

Detailed information about this medicine is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)http://www.aemps.gob.es