VENLAFAXINE COMBIX 75 mg TABLETS

Introduction

PACKAGE LEAFLET: INFORMATION FOR THE USER

Venlafaxine Combix 75 mg film-coated tablets EFG

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.

Contents of the pack

1. What is Venlafaxine Combix and what is it used for
2. What you need to know before you take Venlafaxine Combix
3. How to take Venlafaxine Combix
4. Possible side effects
5. Storage of Venlafaxine Combix
6. Pack contents and further information

1. What is Venlafaxine Combix and what is it used for

Venlafaxine Combix 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 thought that people who are depressed and/or anxious have lower levels of serotonin and noradrenaline in the brain. The exact mechanism of action of antidepressants is not fully understood, but they may help to increase the levels of serotonin and noradrenaline in the brain.

Venlafaxine Combix is a treatment for adults with depression. Treating depressive disorders adequately 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 Venlafaxine Combix

Do not take Venlafaxine Combix

• 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 within the last 14 days any medicines known as irreversible monoamine oxidase inhibitors (MAOIs) used to treat depression or Parkinson's disease. Taking an irreversible MAOI with Venlafaxine Combix can cause serious or potentially life-threatening side effects. Additionally, you must wait at least 7 days after stopping Venlafaxine Combix before taking any irreversible MAOI (see also section “Using Venlafaxine Combix with other medicines” and the information in that section on “Serotonin syndrome”).

Warnings and precautions

Consult your doctor or pharmacist before starting treatment with Venlafaxine Combix.

• If you are using other medicines that, when taken with venlafaxine Combix, may increase the risk of developing serotonin syndrome (see section “Using Venlafaxine Combix with other medicines”).
• 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 a history of seizures (fits).
• If you have a history of low sodium levels in the blood (hyponatremia).
• If you have a tendency to develop bruises or tend to bleed easily (history of bleeding disorders), 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 “Pregnancy, breastfeeding, and fertility”).
• If your cholesterol levels increase.
• 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.
• Diabetes: your blood sugar levels may be altered by venlafaxine. Therefore, the doses of your diabetes medicines may need to be adjusted.

Venlafaxine Combix may cause a feeling of restlessness or difficulty sitting or standing still. You should consult your doctor if this happens to you.

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

If any of these conditions apply to you, consult your doctor before taking Venlafaxine Combix.

Do not drink alcohol during treatment with Venlafaxine Combix, 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 anxiety disorders, you may sometimes have thoughts of harming yourself or suicide. This may increase when you start taking antidepressants, because these medicines take time to work, usually around two weeks, but sometimes longer.

This is more likely to happen:

• 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 disorders who were treated with antidepressants.

If you have thoughts of self-harm or suicide at any time, contact your doctor or go to the emergency department of the nearest 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 tooth decay. Therefore, you should be careful with your dental hygiene.

Use in children and adolescents under 18 years of age

Venlafaxine Combix 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 irritability) when taking this class of medicines. Nevertheless, the doctor 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 prescribes this medicine to a patient under 18 years of age and you wish to discuss this decision, please go back to your doctor. You should inform your doctor if any of the above symptoms develop or worsen when these patients under 18 years of age are taking Venlafaxine Combix. Additionally, the long-term effects on safety and regarding growth, maturation, and cognitive and behavioral development of this medicine have not yet been established.

Using Venlafaxine Combix with other medicines

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 Venlafaxine Combix with other medicines.

Do not start or stop taking any medicines, including those that can be bought without a prescription, natural remedies, and herbal products, before checking with your doctor or pharmacist.

• Irreversible monoamine oxidase inhibitors used to treat depression or Parkinson's disease should not be taken with Venlafaxine Combix. Tell your doctor if you have taken any of these medicines in the last 14 days. (MAOI: See section “What you need to know before you take Venlafaxine Combix”)

• Serotonin syndrome:

A potentially life-threatening condition, or reactions similar to 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)
• medicines for treating depression, e.g., SNRIs, SSRIs, tricyclic antidepressants, or medicines containing lithium
• medicines containing the antibiotic linezolid (used to treat infections)
• medicines containing moclobemide, a reversible MAOI (used to treat depression)
• medicines containing sibutramine (used for weight loss)
• medicines containing tramadol (a pain reliever)
• products containing St. John's Wort (also known as “Hypericum perforatum”, a natural or herbal remedy used to treat mild depression)
• products containing tryptophan (used for problems such as sleep and depression)
• antipsychotics (used to treat a disease with symptoms such as hearing, seeing, or feeling things that do not exist, mistaken beliefs, unusual suspicion, unclear reasoning, and tendency to withdraw).

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

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

The following medicines may also interact with Venlafaxine Combix and should be used with caution. It is especially important to mention to your doctor or pharmacist if you are taking medicines containing:

• ketoconazole (an antifungal medicine)
• haloperidol or risperidone (for treating psychiatric conditions)
• metoprolol (a beta-blocker for treating high blood pressure and heart problems)

Taking Venlafaxine Combix with food, drinks, and alcohol

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

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

Pregnancy, breastfeeding, and fertility

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 Combix after discussing the potential benefits and risks to the unborn child with your doctor.

Make sure your midwife and/or doctor knows you are taking Venlafaxine Combix. When taken during pregnancy, similar medicines (SSRIs) may increase the risk of a serious condition in babies called persistent pulmonary hypertension of the newborn (PPHN), making the baby breathe faster and turn blue. These symptoms usually start during the first 24 hours after the baby is born. If this happens to your baby, you must contact your midwife and/or doctor immediately.

If you are taking this medicine during pregnancy, other symptoms your baby may have when born are feeding problems and breathing problems. If your baby has these symptoms when born and you are worried, contact your doctor and/or midwife who will be able to advise you.

If you take Venlafaxine Combix 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 Combix so they can advise you.

Venlafaxine Combix passes into breast milk. There is a risk of an effect on the baby. Therefore, 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

During treatment with venlafaxine, you may feel drowsy or dizzy. Do not drive or use tools or machines until you know how the treatment with this medicine affects you.

Venlafaxine Combix 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 Venlafaxine Combix

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 is 75 mg per day in divided doses, two or three times a day. Your doctor may gradually increase the dose, and if necessary, even up to a maximum dose of 375 mg per day for depression.

Take Venlafaxine Combix at approximately the same time each day, either in the morning or evening.

Venlafaxine Combix 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 this medicine without consulting your doctor (see section “If you stop taking Venlafaxine Combix”).

If you take more Venlafaxine Combix than you should

Call your doctor or pharmacist immediately if you take more Venlafaxine Combix 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 with the simultaneous intake of certain medicines and/or alcohol (see “Taking Venlafaxine Combix 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 fits, and vomiting.

If you forget to take Venlafaxine Combix

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 more than the daily dose of Venlafaxine Combix that has been prescribed for you in one day.

If you stop taking Venlafaxine Combix

Do not stop taking your treatment or reduce the dose without your doctor's advice, even if you feel better. If your doctor thinks you no longer need Venlafaxine Combix, 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 if the dose is reduced too quickly. Some patients may experience symptoms such as fatigue, dizziness, unsteadiness, 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.

Your doctor will advise you on how to gradually stop taking Venlafaxine Combix. 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 side effects

Like all medicines, Venlafaxine Combix can cause side effects, although not everybody gets them.

Allergic Reactions

If any of the following occur, do not take any more Venlafaxina Combix. Tell your doctor immediately, or go to the emergency room of the nearest hospital:

• Chest tightness, wheezing, difficulty swallowing or breathing
• Swelling of the face, throat, hands, or feet
• Feeling nervous or anxious, dizziness, tingling sensations, sudden reddening of the skin and/or a feeling of heat
• Severe skin rash, itching, or hives (elevated areas of red or pale skin that often itch)
• Signs and symptoms of serotonin syndrome that may include agitation, hallucinations, loss of coordination, rapid heartbeat, increased body temperature, rapid changes in blood pressure, hyperactive reflexes, diarrhea, coma, nausea, vomiting. In its most severe form, serotonin syndrome can resemble Neuroleptic Malignant Syndrome (NMS). The signs and symptoms of NMS may include a combination of fever, rapid heartbeat, sweating, severe muscle stiffness, confusion, increased muscle enzymes (determined by a blood test).

Other adverse effects that you should report to your doctorare:

• Cough, wheezing, shortness of breath, and high temperature.
• Tarry stools (deposits) or blood in stools.
• Yellow eyes or skin, itching, or 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, seizures, or attacks.
• Psychiatric problems, such as hyperactivity and euphoria (unusual feeling of overexcitement).

Withdrawal effects (see section "How to take Venlafaxina Combix, If you stop treatment with Venlafaxina Combix").

• Prolonged bleeding - if you cut yourself or get injured, it may take a little longer than usual for the bleeding to stop.

Complete list of adverse effects

Very common (affects more than 1 in 10 patients)

• Dizziness; headache;
• Nausea; dry mouth.
• Sweating (including night sweats).

Common (affects between 1 and 10 in 100 patients)

• Decreased appetite.
• Confusion; feeling detached (or disconnected) from oneself; lack of orgasm; decreased libido; nervousness; insomnia; abnormal dreams.
• Drowsiness.
• Tremors; tingling; increased muscle tone.
• Visual disturbances including blurred vision; dilated pupils; inability of the eye to automatically change focus from distant to near objects.
• Ringing in the ears (tinnitus).
• Palpitations.
• Increased blood pressure; hot flashes.
• Vomiting; constipation; diarrhea.
• Increased frequency of urination; difficulty urinating.
• Menstrual irregularities, such as increased bleeding or irregular bleeding; abnormal ejaculation/orgasm (men); erectile dysfunction (impotence).
• Weakness (asthenia); fatigue; chills.
• Increased cholesterol.

Uncommon (affects between 1 and 10 in 1,000 patients)

• Hallucinations; feeling detached (or disconnected) from reality; agitation; abnormal orgasm (women); lack of feelings or emotions; feeling overexcited.
• Teeth grinding.
• A feeling of restlessness or inability to sit still or remain quiet; fainting; involuntary muscle movements; altered coordination and balance; altered taste perception.
• Rapid heartbeat; feeling dizzy (especially when getting up too quickly).
• Vomiting blood, tarry stools (deposits) or blood in stools, which may be a sign of internal bleeding.
• Generalized swelling of the skin, especially the face, mouth, tongue, throat area, or hands and feet, and/or relief rash with itching (hives); sensitivity to sunlight; bruising;
• skin rash; abnormal hair loss.
• Inability to urinate.
• Weight gain or loss.

Rare (affects between 1 and 10 in 10,000 patients)

• Seizures or attacks.
• Inability to control urination.
• Hyperactivity, accelerated thoughts, and decreased need for sleep (mania).

Frequency not known

• Reduced number of platelets in the blood leading to an increased risk of bruising or bleeding; blood disorders, e.g., gum bleeding, blood in urine or vomit, or the appearance of unexpected bruises or broken blood vessels (broken veins), which can lead to an increased risk of infection.
• Swelling of the face or tongue, shortness of breath or difficulty breathing, often with skin rashes (this can be a severe allergic reaction).
• Excessive water intake (known as SIADH).
• Decreased sodium levels in the blood.
• Suicidal ideation and suicidal behavior; cases of suicidal ideation and behavior have been reported during treatment with venlafaxine or shortly after stopping treatment (see section 2. "Before taking Venlafaxina Combix").
• Disorientation and confusion often accompanied by hallucinations (delirium); aggression.
• A high temperature with stiff muscles, confusion, or agitation, and sweating, or if you experience jerky muscle movements that you cannot control, may be symptoms of serious conditions known as neuroleptic malignant syndrome: euphoric feelings, drowsiness, rapid and sustained eye movement, clumsiness, restlessness, feeling drunk, sweating, or stiff muscles, which are symptoms of serotonin syndrome; stiffness; spasms and involuntary muscle movements.

• Severe eye pain and reduced or blurred vision.

• Dizziness.
• Decreased blood pressure; abnormal, rapid, or irregular heartbeat, which can lead to fainting.
• Cough, difficult breathing, shortness of breath, and high temperature, which are symptoms of lung inflammation associated with an increase in white blood cells (pulmonary eosinophilia).
• Severe back or abdominal 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), slight changes in blood levels of liver enzymes.
• Skin rash that can lead to severe blistering and peeling of the skin; itching; mild skin rash
• Unexplained muscle pain, discomfort, or weakness (rhabdomyolysis).
• Abnormal milk production.
• Excessive vaginal bleeding shortly after childbirth (postpartum hemorrhage), see "Pregnancy, breastfeeding, and fertility" in section 2 for more information.

Venlafaxina Combix 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, Venlafaxina Combix 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 Venlafaxina Combix 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 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 Venlafaxina Combix

Keep this medicine out of 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.

No special storage conditions are required.

Medicines should not be thrown away in drains or trash. Deposit the packaging and medicines you no longer need in the SIGRE Point of the pharmacy. In case of doubt, ask your pharmacist how to dispose of the packaging and medicines you no longer need. This way, you will help protect the environment.

6. Package contents and additional information

Venlafaxina Combix composition

The active ingredient is venlafaxine. Each tablet contains 84.84 mg of venlafaxine hydrochloride equivalent to 75 mg of venlafaxine.

The other components (excipients) are: microcrystalline cellulose (E460i), lactose monohydrate, sodium starch glycolate, magnesium stearate (E470b), yellow iron oxide (E172), and brown iron oxide (E172).

Appearance of Venlafaxina Combix and package contents

Venlafaxina Combix 75 mg is presented in the form of oblong tablets of beige color, speckled, scored on one side and smooth on the other.

Venlafaxina Combix 75 mg is presented in packages containing 60 tablets.

Marketing authorization holder and manufacturer

Marketing authorization holder

Laboratorios Combix, S.L.U.

C/ Badajoz 2. Edificio 2.

28223 Pozuelo de Alarcón (Madrid)

Spain

Manufacturer

Combino Pharm S.L.

Fructuós Gelabert 6-8

08970 Sant Joan Despí

Barcelona

SPAIN

OR

Combino Pharm (Malta) Ltd.

HF 60, Hal Far Industrial Estate

BBG07 Hal Far

MALTA

OR

ZYDUS FRANCE

Zac Les Hautes Pâturages

Parc d´Activités des Pleupliers

25 rue des Pleupliers

92000 Nanterre (France)

OR

Centre Spécialités Pharmaceutiques

ZAC des Suzots

35 rue de la Chapelle

63450 Saint Amant Tallende

France

This prospectus was approved in May 2023.

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