ZARELIS RETARD 75 mg PROLONGED-RELEASE TABLETS

Introduction

Package Leaflet: Information for the User

ZARELIS Retard 75 mg prolonged-release tablets

venlafaxine

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you

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

Contents of the pack and other information

1. What is Zarelis Retard and what is it used for
2. What you need to know before you take Zarelis Retard
3. How to take Zarelis Retard
4. Possible side effects
5. Storage of Zarelis Retard

1. Contents of the pack and further information.

1. What is Zarelis Retard and what is it used for

Zarelis Retard contains the active substance venlafaxine.

Zarelis Retard is an antidepressant that belongs to a group of medicines called serotonin and norepinephrine reuptake inhibitors (SNRIs). This group of medicines is used to treat depression and other conditions such as anxiety disorders. It is not fully understood how antidepressants work, but they may help to increase the 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) and panic disorder (panic attacks). Treating depressive and anxiety disorders properly is important to help you feel better. If left untreated, your condition may not improve or may worsen and become more difficult to treat.

2. What you need to know before you take Zarelis Retard

Do not take Zarelis Retard

• If you are allergic to venlafaxine or any of the other ingredients of this medicine (listed in section 6).
• If you are also taking or have taken in the last 14 days, any medicinal product known as an irreversible monoamine oxidase inhibitor (MAOI), used to treat depression or Parkinson's disease. Taking an irreversible MAOI with venlafaxine can cause serious or potentially life-threatening side effects. Additionally, you must wait at least 7 days after you stop taking venlafaxine before taking any irreversible MAOI (see also the section entitled “Other medicines and Zarelis Retard” and the information in that section on “Serotonin syndrome”).

Warnings and precautions

Talk to your doctor or pharmacist before starting to take venlafaxine

• If you are taking other medicines that, when taken with venlafaxine, could increase the risk of developing Serotonin syndrome (see the section “Other medicines and Zarelis Retard”).
• If you have a swallowing, stomach or intestinal disorder that reduces your ability to swallow or pass food through the normal movements of the intestine.
• 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 bruises or tendency to bleed easily) or 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 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.

Venlafaxine may cause a feeling of restlessness or difficulty sitting or standing still during the first few weeks of treatment. You should consult your doctor if this happens to you.

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

Suicidal thoughts 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 or killing yourself. These thoughts may increase when you first start taking antidepressants, because all these medicines take time to work, usually around two weeks but sometimes longer. These thoughts may also occur when you reduce your dose or during the end of treatment with venlafaxine.

This is more likely to happen:

• If you have previously had thoughts of suicide or self-harm.
• If you are a young adult. Information from clinical trials has shown an increased risk of suicidal behavior in young adults (less than 25 years of age) with psychiatric conditions who were treated with antidepressants.

If you have thoughts of self-harm or suicide at any time, contact your doctor or go to the hospital directly.

You may find it helpful to tell a relative or close friend that you are depressed or have an anxiety disorder and ask them to read this leaflet. You may also ask them to tell you if they think your depression or anxiety is getting worse, or if they are worried 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 be careful with your dental hygiene.

Diabetes

Your blood sugar levels may be altered due to venlafaxine. Therefore, it may be necessary to adjust the dose of the medicine used for diabetes.

Sexual problems

Some medicines in the same group as venlafaxine (called SNRIs) may cause symptoms of sexual dysfunction (see section 4). In some cases, these symptoms persist after stopping treatment.

Children and adolescents

Venlafaxine should not normally be used in the treatment of children and adolescents under 18 years of age. Additionally, you should know that in patients under 18 years of age, there is a greater risk of side effects such as suicidal attempts, suicidal thoughts, and hostility (mainly aggression, confrontational behavior, and irritation) when taking this class of medicines. Nevertheless, the doctor who prescribes it to you may prescribe this medicine to patients under 18 years of age when they decide it is the most convenient for the patient. If the doctor who prescribes it to you has prescribed this medicine to a patient under 18 years of age and you want to discuss this decision, please go back to your doctor. You must inform your doctor if any of the above symptoms develop or worsen when these patients under 18 years of age are taking venlafaxine. Additionally, the long-term effects on safety, including effects on growth, maturity, and cognitive and behavioral development, of this medicine have not yet been demonstrated.

Other medicines and Zarelis Retard

Tell your doctor or pharmacist if you are using, have recently used, or might use any other medicines.

Your doctor must decide if you can take Zarelis Retard with other medicines.

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

• Monoamine oxidase inhibitors, used to treat depression or Parkinson's disease, must not be used with venlafaxine.Tell your doctor if you have taken these medicines in the last 14 days (MAOI: see section “What you need to know before you take Zarelis Retard”)
• Serotonin syndrome:

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

Examples of these medicines include:

• Triptans (used for migraine)
• Other medicines for treating depression, for example, SNRIs, SSRIs, tricyclic antidepressants, or medicines containing lithium
• Medicines containing amphetamines (used to treat attention deficit hyperactivity disorder (ADHD), narcolepsy, and obesity)
• Medicines containing the antibiotic linezolid (used to treat infections)
• Medicines containing moclobemide, an MAOI (used to treat depression)
• Medicines containing sibutramine (used for weight loss)
• Medicines containing opioids (e.g., buprenorphine, tramadol, fentanyl, tapentadol, pethidine, or pentazocine) (used to treat severe pain).
• Medicines containing dextromethorphan (used to treat cough)
• Medicines containing methadone (used to treat opioid addiction or severe pain)
• Medicines containing methylthioninium chloride (methylene blue) (used to treat high levels of methemoglobin 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 disease with symptoms of auditory, visual, or perceptual unreality, false beliefs, unusual distrust, confused reasoning, and onset of withdrawal)

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, overactive reflexes, diarrhea, coma, nausea, vomiting.

Serotonin syndrome, in its most severe form, can resemble Neuroleptic Malignant Syndrome (NMS). The symptoms and signs of NMS can include a combination of fever, rapid heartbeat, sweating, severe muscle stiffness, confusion, increased level of muscle enzymes (determined in blood).

Tell your doctor immediately or go to the hospital if you think you are suffering from Serotonin syndrome.

You must tell your doctor if you are taking medicines that affect your heart rhythm.

Examples of these medicines include:

• Antiarrhythmics such as quinidine, amiodarone, sotalol, or dofetilide (used to treat irregular heartbeat).
• 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 medicines may also interact with venlafaxine and should be used with caution. It is especially important to tell your doctor or pharmacist if you are taking medicines containing:

• Ketoconazole (antifungal medicines).
• Haloperidol or risperidone (for treating psychiatric conditions).
• Metoprolol (a beta-blocker for treating high blood pressure and heart problems).

Using 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, if you think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine. You should only take venlafaxine after discussing with your doctor the possible benefits and risks to the unborn child.

Make sure your midwife and/or doctor knows that you are using venlafaxine. When similar medicines (called selective serotonin reuptake inhibitors: SSRIs) are taken during pregnancy, there may be an increased risk that the baby will suffer from a serious disease called persistent pulmonary hypertension of the newborn (PPHN), causing the child to breathe more rapidly and appear blue. These symptoms usually start during the first 24 hours after birth. If this happens to you, you must contact a doctor and/or midwife immediately.

If you take venlafaxine in the late stage 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 venlafaxine so they can advise you.

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

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

Driving and using machines

Do not drive or use tools or machines until you know how venlafaxine affects you.

Zarelis Retard contains lactose

If your doctor has told you that you have an intolerance to some sugars, consult them before taking this medicine.

3. How to take Zarelis Retard

Follow exactly the administration instructions of this medicine given by your doctor or pharmacist. In case of doubt, consult your doctor or pharmacist again.

The usual recommended initial 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, increase 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 gradually increase the dose. The maximum dose for generalized anxiety disorder, social anxiety disorder, and panic disorder is 225 mg/day.

Take venlafaxine at approximately the same time each day, either in the morning or evening. 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 it may be necessary that your dose of this medicine is different.

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

If you take more Zarelis Retard than you should

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

Overdose can put your life in danger, especially when taken with certain medicines and/or alcohol (see “Taking Zarelis Retard with other medicines”).

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

If you forget 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 a single dose as usual. Do not take a double dose to make up for a forgotten dose. Do not take more than the daily dose of venlafaxine that has been prescribed for you in one day.

If you stop taking Zarelis Retard

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

Your doctor will advise you on how to gradually stop treatment with venlafaxine. This may take several weeks or months. In some patients, the discontinuation 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 medicine, ask your doctor or pharmacist.

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them.

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

Uncommon (may affect up to 1 in 100 people)

• Swelling of the face, mouth, tongue, throat, hands, or feet and/or swollen rash with itching, difficulty swallowing or breathing.

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

• Chest oppression, wheezing, difficulty swallowing or breathing.
• Severe skin rash, itching, or hives (elevated areas of red or pale skin that often itch).
• Signs and symptoms 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, vomiting.

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

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

Frequency unknown (cannot be estimated from available data)

• Signs and symptoms 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 about include (the frequency of these adverse effects is included in the list below “other side effects that may occur”):

• Cough, breathing noise, and difficulty breathing that may be accompanied by an increased temperature.
• Tarry stools (deposits) 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, increased blood pressure.
• Eye problems, such as blurred vision, dilated pupils.
• Nervous system problems: such as dizziness, tingling, movement disorder (muscle spasms and stiffness), convulsions, or seizures.
• Psychiatric problems, such as hyperactivity and euphoria (unusual overexcitement).
• Withdrawal effects (see section “How to take Zarelis Retard, If you stop treatment with Zarelis Retard”).
• Prolonged bleeding – If you cut or injure yourself, the bleeding may take a little longer than usual to stop.

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 Adverse Effects That May Occur

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

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

Common (may affect up to 1 in 10 people)

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

Uncommon (may affect up to 1 in 100 people)

• Hyperactivity, accelerated thoughts, and decreased need for sleep (mania).
• Hallucinations; feeling separated (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 getting up too quickly), decreased coordination and balance.
• Vomiting blood, tarry stools (deposits) or blood in the stool, which may be a sign of internal bleeding.
• Sensitivity to sunlight, bruising, rash.
• Inability to control urination.
• Stiffness, spasms, and involuntary muscle movements. Slight changes in blood levels of liver enzymes.

Rare (may affect 1 in 1,000 patients)

• Seizures or convulsions.
• Cough, breathing noise, and shortness of breath 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 heartbeat, rapid or irregular, which can 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, 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 be due to a reduced number of platelets in the blood, leading to an increased risk of bruising or bleeding.
• Abnormal milk production.
• Unexpected bleeding, for example, bleeding from the gums, blood in the urine or vomit, or the appearance of bruising or broken blood vessels (broken veins).

Frequency unknown (cannot be estimated from available data)

• Suicidal thoughts and behavior. Cases of suicidal thoughts and behavior have been reported during therapy with venlafaxine or immediately after discontinuation of treatment (see section 2, What you need to know before you start taking Zarelis Retard).
• Aggression.
• Dizziness.
• Excessive vaginal bleeding shortly after childbirth (postpartum hemorrhage), see “Pregnancy and lactation” in section 2 for more information.

Venlafaxine sometimes produces unwanted effects that you may not be aware of, such as increased blood pressure or an abnormal heartbeat; slight changes in blood levels of liver enzymes, sodium, or cholesterol. Less frequently, Zarelis Retard may reduce the function of blood platelets, leading to an increased risk of bruising or bleeding. Therefore, your doctor may want to perform occasional blood tests, especially if you have been taking Zarelis Retard for a long time.

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

Reporting of adverse effects

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

5. Storage of Zarelis Retard

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

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

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

Do not throw any medicine down the drain or into the trash. Deposit the packaging and medicines that you no longer need at the SIGRE collection point in the pharmacy. If in doubt, ask your pharmacist how to dispose of the packaging and medicines that you no longer need. This way, you will help protect the environment.

6. Package contents and additional information

Zarelis Retard Composition

The active ingredient is venlafaxine.

Each tablet contains 75 mg of venlafaxine (as hydrochloride).

The other ingredients are:

Core: mannitol (E421), povidone K-90, macrogol 400, microcrystalline cellulose (E 460(i)), colloidal anhydrous silica, magnesium stearate (E 470b).

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

Product appearance and package contents

Prolonged-release tablets 7.5 mm, round, biconvex, white.

Zarelis Retard 75 mg is available in blisters of 10, 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 pack sizes may be marketed.

Marketing authorization holder:

ITALFARMACO, S.A.

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

Tel.: 916572323

Manufacturer:

Laboratorios LICONSA, S.A.

Avda. Miralcampo, Nº 7, Polígono Industrial 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 21, 8054 Graz,

Austria

This medicine is authorized in the Member States of the European Economic Area under the following names:

Date of last revision of this prospectus:February 2025

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