Leaflet: information for the user

ZARELIS Retard 37.5 mg prolonged-release tablets

venlafaxine

Read this leaflet carefully before you start to take this medicine because it contains important information for you.

• Keep this leaflet, 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; do not give it 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 leaflet. See section 4.

6. Contents of the pack and additional information.

Zarelis Retard contains the active ingredient venlafaxine.

Venlafaxine 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 noradrenaline 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) 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 components of this medication (listed in section 6).
• If you take or have taken in the last 14 days irreversible monoamine oxidase inhibitors (IMAOs), used to treat depression or Parkinson's disease. Taking IMAOs with venlafaxine may cause severe and even life-threatening side effects. Additionally, you should wait at least 7 days after stopping venlafaxine before taking any IMAO (see also the section "Other medications and Zarelis retard" and the information in this section on "Serotonin syndrome").

Warnings and precautions

Consult your doctor or pharmacistbeforestarting to take this medication:

• If you are taking other medications that, taken with venlafaxine, 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 eye pressure).
• If you have a history of high blood pressure.
• If you have a history of heart problems.
• If you have been informed of abnormal heart arrhythmias.
• 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 petechiae or tendency to bleed easily) or if you are taking other medications that may increase the risk of bleeding, such as warfarin (used to prevent blood clots) or if you are pregnant (see the 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 restlessness or an inability to sit or stand still during the first few weeks of treatment. You should consult your doctor if this occurs.

Do not drink alcohol during treatment with venlafaxine, 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 depression or anxiety disorder

If you are depressed and/or have anxiety disorders, you may have thoughts of self-harm or suicide. These thoughts may increase when you start taking antidepressants, as all these medications take time to take effect, usually two weeks but sometimes longer. These thoughts may also occur when your dose is reduced or during the discontinuation of treatment with venlafaxine.

You may be more likely to have these thoughts:

• If you have had previous thoughts of suicide or self-harm.
• If you are a young adult. The information from clinical trials has shown an increased risk of suicidal behavior in young adults (less than 25 years old) with psychiatric conditions 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 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 worsening, 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 good care of your dental hygiene.

Diabetes

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

Sexual problems

Some medications, such as venlafaxine (called SSRIs), may cause symptoms of sexual dysfunction (see section 4). In some cases, these symptoms persist after stopping treatment.

Children and adolescents

Venlafaxine should not be used normally in the treatment ofchildren and adolescents under 18 years old. Additionally, you should know that patients under 18 years oldhave agreater risk of side effects such as suicidal behavior,suicidal thoughtsand hostility (predominantly aggression, confrontational behavior and anger).

Despite this, your doctor may prescribe this medication to patients under 18 years old when they decide it is the best option for the patient. If your doctor has prescribed this medication to a patient under 18 years old and you want to discuss this decision,please consult withyour doctor again. You should inform your doctor if any of the symptoms listed above appear or worsen in these patients under 18 years old who are taking venlafaxine. Additionally, the long-term effects of this medication on growth, maturation and cognitive development in this age group have not been demonstrated.

Other medications and Zarelis Retard

Inform your doctor or pharmacist if you are taking, have taken recently or may need to take any other medication.

Your doctor should decide if you can take venlafaxinewith other medications.

Do not start or stop taking another medication, including those available over the counter, natural remedies and herbal products, before consulting with your doctor or pharmacist.

• Inhibitors of monoamine oxidase, used to treat depression or Parkinson's disease,should not be used with venlafaxine.Inform your doctor if you have taken these medications in the last 14 days (IMAOs: see the section "What you need to know before starting to take Zarelis Retard").
• Serotonin syndrome:

A potentially fatal condition, or Serotonin Syndrome (SS), may occur with treatment with venlafaxine, particularly when taken with other medications.

Examples of these medications include:

• Triptans (used for migraines)
• Other medications for depression, such as SSRIs, SNRIs, 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 (such as 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 high levels of methemoglobin in the blood)
• Products containing St. John's Wort (also known asHypericum 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 conditions with symptoms such as hearing, seeing or feeling things that are not real, false beliefs, unusual suspicion, unclear thinking and retraction)

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, vomiting.

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

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

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

Examples of these medications include:

• Antiarrhythmics such as quinidine, amiodarone, sotalol or dofetilide (used to treat abnormal heart rhythms).
• 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 venlafaxineand 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 conditions).
• Metoprolol (a beta-blocker used to treat high blood pressure and heart problems).

Use of Zarelis Retard with food, drinks and alcohol

Venlafaxineshould 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 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, consult your doctor or pharmacist before taking this medication. You should only take venlafaxineafter discussing with your doctor the possible benefits and risks for the unborn child.

Make sure your midwife and/or doctor know that you are taking venlafaxine. When you take similar medications (SSRIs) during pregnancy, you may increase the risk of the baby developing 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 your baby, you should contact a doctor and/or midwife immediately.

If you take venlafaxine in the final stages of pregnancy, you may increase the risk of excessive 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 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 problems. If your baby has these symptoms when born and you are concerned, contact your doctor and/or midwife who can advise you.

Venlafaxinepasses into breast milk. There is a risk of effect on the baby, so you should consult with your doctor and they will decide if you should stop breastfeeding or stop taking this medication.

Driving and operating machines

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

Zarelis Retard contains lactose

If your doctor has told you that you have intolerance to certain sugars, consult your doctor before taking this medication.

Follow exactly the administration instructions of this medication as indicated by your doctor. In case of doubt, consult your doctor or pharmacist again.

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

Venlafaxine should be taken with food.

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

Do not stop taking venlafaxine 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.

Overdose can be life-threatening, especially with the simultaneous use of certain medications and/or alcohol (see “Other medications and Zarelis Retard”).

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

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

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 the missed doses. Do not take more than the daily dose of venlafaxine 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 believes you no longer need venlafaxine, they may ask you to reduce the dose gradually before interrupting 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, numbness or, in rare cases, electric shock 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 discontinue treatment with venlafaxine. 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 bothersome symptoms, consult your doctor for further guidance.

If you have any other doubts about the use of this medication, ask your doctor or pharmacist.

Like all medications, this medication may cause side effects, although not everyone will experience them.

If any of the following effects occur, do not take more venlafaxine.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 inflamed skin, difficulty swallowing or breathing.

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

• Pressure in the chest, 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 Neuroleptic Malignant Syndrome (NMS). The symptoms and signs of NMS 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, tremors, headache, sweating, or symptoms similar to the flu. This may be due to a blood disorder that can increase the risk of infection.
• Severe skin rash, which may lead to 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.

You should inform your doctor of any other side effects you experience (the frequency of these side effects is included in the following list "Other side effects that may occur"):

• Coughing, wheezing, and difficulty breathing, which may be accompanied by an increased temperature.
• Black stools 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 heartbeats, increased blood pressure.
• Eye problems, such as blurred vision, dilated pupils.
• Nervous system problems, such as dizziness, numbness, movement disorder (muscle spasms or rigidity), convulsions, or seizures.
• Psychiatric problems, such as hyperactivity and unusual overexcitement.
• Withdrawal symptoms from treatment (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 longer than usual to stop.
• Heavy vaginal bleeding after childbirth (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 medication. 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 medication dose has been absorbed.

Other side effects that may occur

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

• Dizziness, headache, somnolence.
• Insomnia.
• Nausea, dry mouth, constipation.
• Sweating (including night sweats).

Common (may affect up to 1 in 10 people)

• Loss of appetite.
• Confusion; feeling detached (or disconnected) from oneself, anorgasmia, decreased libido, agitation, nervousness, abnormal dreams.
• Tremor, a feeling of restlessness or inability to sit or remain still; paresthesia; alteration of taste; increased muscle tone.
• Eye problems, including blurred vision, dilated pupils, difficulty focusing from far to near.
• Tinnitus (ringing in the ears).
• 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 (men), erectile dysfunction (impotence).
• Weakness (asthenia), fatigue, chills.
• Weight gain or loss.
• Increased cholesterol.

Rare (may affect up to 1 in 100 people)

• Hyperactivity, accelerated thoughts, and decreased need for sleep (mania).
• Hallucinations; feeling detached (or disconnected) from reality; abnormal orgasm; lack of feelings or emotions; overexcitement or euphoria; bruxism.
• Fainting; involuntary muscle movements; alteration of coordination and balance.
• Feeling dizzy (especially when standing up too quickly); increased blood pressure.
• Vomiting blood, black stools or blood in the stool, which may be a sign of internal bleeding.
• Sensitivity to sunlight, bruises, abnormal hair loss.
• Inability to control urination.
• Rigidity, spasms, and involuntary muscle movements.
• Mild changes in liver enzyme levels.

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

• Convulsions or seizures.
• Coughing, wheezing, and difficulty breathing, which may be accompanied by a high temperature.
• Disorientation and confusion, often accompanied by hallucinations (delirium).
• SIADH (excessive water intake).
• Decreased sodium levels in the blood.
• Severe eye pain and reduced or blurred vision.
• Abnormal heartbeats, rapid or irregular heartbeats, 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, leading to an increased risk of ecchymoses or bleeding.
• Abnormal milk production.
• Unexpected bleeding, such as bleeding gums, blood in urine or vomit, or the appearance of ecchymoses 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 venlafaxine therapy or shortly after discontinuation of treatment (see section 2, What you should know before starting to take Zarelis Retard).
• Aggression.
• Dizziness.
• Heavy vaginal bleeding after childbirth (postpartum hemorrhage), see section 2 "Pregnancy and breastfeeding" for more information.

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

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 the Spanish 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 medication.

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

Do not use this medication after the expiration date that appears on the box after “CAD”. The expiration date is the last day of the month indicated.

This medication 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.

Medications should not be disposed of through drains or trash. Deposit the containers and medications you no longer need at the SIGRE point of the pharmacy. 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 principle is venlafaxine.

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

The other components (excipients) are:

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

Appearance of the product and content of the container

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

Zarelis Retard 37.5 mg is available in blisters of10, 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.

Only some sizes of containers may be commercially marketed.

Holder of the marketing authorization and responsible for manufacturing

Holder of the marketing authorization:

ITALFARMACO, S.A.

San Rafael, 3 – 28108 Alcobendas (Madrid),

Spain

Responsible for manufacturing:

Laboratorios LICONSA, S.A.

AvenidaMiralcampo, Nº 7, Industrial Park Miralcampo

19200 Azuqueca de Henares (Guadalajara),

Spain

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

Sweden: Venlafaxin Liconsa 37.5 mg prolonged-release tablets

Spain: Zarelis Retard 37.5 mg prolonged-release tablets

Germany: Venlafaxin AAA-Pharma 37.5 mg Retard tablets

Finland: Venlafaxin Sandoz 37.5 mg prolonged-release tablets

Date of the last review of this leaflet:11/2024

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