ZARELIS RETARD 37.5 mg PROLONGED-RELEASE TABLETS

Introduction

Package Leaflet: Information for the User

ZARELIS Retard 37.5 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 Zarelis Retard is and what it is used for
2. What you need to know before you take Zarelis Retard
3. How to take Zarelis Retard
4. Possible side effects
5. Storing Zarelis Retard

1. Contents of the pack and further information.

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

Zarelis Retard contains the active substance venlafaxine.

Venlafaxine 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.

Venlafaxine is a treatment for adults with depression. Venlafaxine 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 depression and anxiety disorders properly is important to help you feel better. If left untreated, your condition may not improve or may get worse 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 taking or have taken in the last 14 days irreversible monoamine oxidase inhibitors (MAOIs), used to treat depression or Parkinson's disease. Taking MAOIs with venlafaxine can cause serious and potentially life-threatening side effects. Also, you must wait at least 7 days after stopping venlafaxine before taking any MAOI (see also section “Other medicines and Zarelis Retard” and the information in this section on “Serotonin syndrome”).

Warnings and precautions

Consult your doctor or pharmacist before starting to take this medicine:

• If you are taking other medicines that, when taken with venlafaxine, could increase the risk of developing serotonin syndrome (see 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 been informed that you have abnormal heart rhythms.
• If you have a history of seizures (fits).
• 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 a family member 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 an inability to sit or stand 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 venlafaxine, as it may cause extreme fatigue and unconsciousness. Taking it with certain medicines and/or alcohol may worsen 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 yourself or suicide. 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 your dose is reduced or when you stop taking venlafaxine.

You may be more likely to think this way:

• If you have previously had thoughts of suicide or self-harm.
• If you are a young adult. Clinical trial data have 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 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 might 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 by venlafaxine. Therefore, it may be necessary to adjust the dose of your diabetes medication.

Sexual problems

Some medicines like 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. Also, you should know that patients under 18 have an increased risk of side effects such as suicide attempts, suicidal thoughts, and hostility (mainly aggression, confrontational behavior, and anger) when they take this class of medicines.

Despite this, your doctor may prescribe this medicine to patients under 18 when they decide that it is the best for the patient. If your doctor has prescribed this medicine to a patient under 18 and you wish to discuss this decision, please consult your doctor again. You should inform your doctor if any of the above symptoms appear or worsen when these patients under 18 are taking venlafaxine. Also, the long-term safety effects of this medicine regarding growth, maturation, and cognitive development in this age group have not been demonstrated.

Other medicines and Zarelis Retard

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 venlafaxine with other medicines.

Do not start or stop taking any other medicines, including those that can be bought without a prescription, herbal remedies, and supplements, before consulting your doctor or pharmacist.

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

A potentially life-threatening condition, or Neuroleptic Malignant Syndrome (NMS), (see section “Possible side effects”), may occur with venlafaxine treatment, 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 herbal remedy or supplement used to treat mild depression)
• Products containing tryptophan (used for problems such as sleep and depression)

• Antipsychotics (used to treat a condition with symptoms such as hearing, seeing, or feeling things that are not real, mistaken beliefs, unusual suspicion, unclear reasoning, and 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 levels of muscle enzymes (determined in blood).

Tell your doctor immediately or go to the emergency department of the nearest hospital if you think you are experiencing serotonin syndrome.

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

Examples of these medicines include:

• Anti-arrhythmics such as quinidine, amiodarone, sotalol, or dofetilide (used to treat abnormal heart rhythms).
• Antipsychotics such as thioridazine (see also above section “Serotonin syndrome”).
• Antibiotics such as erythromycin or moxifloxacine (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 mention to your doctor or pharmacist if you are taking medicines containing:

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

Using Zarelis Retard with food, drinks, and alcohol

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

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

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, 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 the potential benefits and risks with your doctor.

Make sure your midwife and/or doctor knows you are taking venlafaxine. When you take similar medicines (SSRIs) during pregnancy, it may increase the risk of your baby having a serious condition called persistent pulmonary hypertension of the newborn (PPHN), causing the baby to breathe faster and appear blue. These symptoms usually start during the first 24 hours after birth. If this happens to your baby, you should contact a doctor and/or midwife immediately.

If you take venlafaxine 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 venlafaxine so they can advise you.

If you are taking this medicine during pregnancy, other symptoms your baby may have when born are problems with feeding and problems with breathing. 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 consult your doctor and they will decide whether you should stop breastfeeding or stop treatment with 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 your doctor before taking this medicine.

3. How to take Zarelis Retard

Take this medicine exactly as your doctor has told you. If you are not sure, check with 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, 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 in the evening. The tablets should be swallowed whole with liquids and should not be divided, crushed, chewed, or dissolved.

Venlafaxine should be taken with food.

If you have liver or kidney problems, consult your doctor, as you may need a different dose of this medicine.

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 of this medicine than your doctor prescribed.

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

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

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicology Information Service, phone 91 562 04 20, indicating the medicine and the amount taken.

If you forget to take Zarelis Retard

If you miss 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 forgotten doses. Do not take more than the daily dose of venlafaxine that your doctor has prescribed in one day.

If you stop taking 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 venlafaxine, they may ask you to reduce the dose gradually before stopping treatment completely. It is known that side effects occur when people stop using this medicine, especially when it is stopped suddenly or 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, seizures, or flu-like symptoms, vision problems, and increased blood pressure (which can cause headache, dizziness, ringing in the ears, sweating, etc.).

Your doctor will advise you on how to gradually stop taking venlafaxine. This may take several weeks or months. In some patients, the discontinuation may need to be done very gradually 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 tightness, 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 heartbeat, 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 heartbeat, sweating, severe muscle stiffness, confusion, increased levels of muscle enzymes (determined by a blood test).

• Signs of infection, such as increased temperature, chills, tremors, 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 severe blisters and skin peeling.
• Unexplained muscle pain, discomfort, or weakness. This may be a sign of rhabdomyolysis.

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

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

Other adverse effects that you should report to your doctor include(the frequency of these adverse effects is included in the following list “Other adverse 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 heartbeat, increased blood pressure.
• Eye problems, such as blurred vision, dilated pupils.
• Nervous system problems, such as dizziness, tingling, movement disorder (muscle spasms or stiffness), convulsions, or seizures.
• Psychiatric problems, such as hyperactivity and unusual overexcitement.
• Effects of treatment withdrawal (see section “How to take Zarelis Retard, If you interrupt 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 form 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 sit or stay still; tingling; altered sense of taste; increased muscle tone.
• Eye disorders including blurred vision, dilated pupils, difficulty focusing 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 standing up too quickly); increased blood pressure.
• Vomiting blood, tarry stools (deposits), or blood in the stool, which may be a sign of internal bleeding.
• Sensitivity to sunlight, bruising, abnormal hair loss.
• Inability to control urination.
• Stiffness, spasms, and involuntary muscle movements.
• Mild changes in blood levels of liver enzymes.

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

• Seizures or convulsions.
• Cough, breathing noise, 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, rapid, or irregular heartbeat that 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, 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 that leads 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 not known (cannot be estimated from the available data)

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

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

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 is not listed in this leaflet. 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 box after “EXP”. The expiration date is the last day of the month indicated.

This medicine does not require any special storage temperature.

Blister: Store in the original packaging to protect it from moisture.

Bottle: Keep the bottle properly closed to protect it from moisture.

Medicines should not be disposed of through wastewater or household waste. Deposit the packaging and medicines that you no longer need at the SIGRE collection point in the pharmacy. Ask your pharmacist how to dispose of the packaging and medicines that you no longer need. This will help protect the environment.

6. Package Contents and Additional Information

Composition of Zarelis Retard

The active ingredient is venlafaxine.

Each prolonged-release tablet contains 37.5 mg of venlafaxine (as hydrochloride).

The other ingredients (excipients) are:

• Core: mannitol (E421), povidone K-90, macrogol 400, microcrystalline cellulose (E 460(i)), colloidal anhydrous silica, and magnesium stearate (E 470b).
• Coating material: cellulose acetate, macrogol 400, hypromellose, lactose monohydrate, titanium dioxide (E171), and triacetin.

Appearance of the Product and Package Contents

The 37.5 mg prolonged-release tablets are 7 mm, round, biconvex, and white.

Zarelis Retard 37.5 mg is available in blisters of 10, 14, 20, 28, 30, 50, 56, 60, 100, and 500 tablets; and in plastic bottles of 10, 14, 20, 28, 30, 50, 56, 60, 100, and 500 tablets.

Not all pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder:

ITALFARMACO, S.A.

San Rafael, 3 – 28108 Alcobendas (Madrid),

Spain

Manufacturer:

LICONSA Laboratories, S.A.

Miralcampo Avenue, No. 7, Miralcampo Industrial Estate

19200 Azuqueca de Henares (Guadalajara),

Spain

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

Date of the last revision of this leaflet: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

Other Sources of Information

Detailed information about this medicine is available on the website of the European Medicines Agency: https://www.ema.europa.eu