VENLAFAXINE RETARD PHARMA COMBIX 75 mg PROLONGED-RELEASE HARD CAPSULES

Introduction

Package Leaflet: Information for the User

Venlafaxine Retard Pharma Combix 75 mg prolonged-release hard capsules 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 experience 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

1. What is Venlafaxine Retard Pharma Combix and what is it used for
2. What you need to know before you take Venlafaxine Retard Pharma Combix
3. How to take Venlafaxine Retard Pharma Combix
4. Possible side effects
5. Storage of Venlafaxine Retard Pharma Combix
6. Contents of the pack and other information

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

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

Venlafaxine Retard is a treatment for adults with depression. It is also a treatment for adults with the following anxiety disorders: generalized anxiety disorder, social anxiety disorder (fear or avoidance of social situations), 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 Venlafaxine Retard Pharma Combix

Do not take Venlafaxine Retard Pharma 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 Retard can cause serious or even life-threatening side effects. Also, you must wait at least 7 days after stopping Venlafaxine Retard before taking any MAOI (see also section “Taking other medicines” and the information in that section on “Serotonin Syndrome”).

Warnings and precautions

Consult your doctor or pharmacist before starting treatment with Venlafaxine Retard:

• If you are taking other medicines that, when taken with Venlafaxine Retard, could increase the risk of developing serotonin syndrome (see section “Taking Venlafaxine Retard 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 been told that your heart rhythm is abnormal.
• If you have a history of seizures (fits).
• If you have a history of low sodium levels in your blood (hyponatraemia).
• If you have a tendency to develop bruises or have a tendency to bleed easily (history of bleeding disorders), or if you are taking other medicines that may increase the risk of bleeding, e.g. warfarin (used to prevent blood clots), or if you are pregnant (see “Pregnancy, breast-feeding and fertility”).
• If you have a history of mania or bipolar disorder (feeling overexcited or elated).
• If you have a history of aggressive behaviour.

Venlafaxine Retard 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.

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

Do not drink alcohol while taking Venlafaxine Retard Pharma Combix, as it may cause extreme tiredness and unconsciousness. Taking it with certain medicines and/or with alcohol may worsen the symptoms of depression and other conditions, such as anxiety disorders.

Thoughts of suicide and worsening of your depression or anxiety disorder

If you are depressed and/or have an anxiety disorder, you may sometimes have thoughts of harming or killing yourself. These may be increased when first starting treatment with antidepressants, since these medicines all take time to work, usually about 2 weeks, but sometimes longer.

This is more likely to happen:

• If you have previously had thoughts about killing or harming yourself.
• If you are a young adult. Information from clinical trials has shown an increased risk of suicidal behaviour in adults aged less than 25 years with psychiatric conditions who were treated with an antidepressant.

If you have thoughts of harming or killing yourself at any time, contact your doctor or go to a hospital straight away.

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 behaviour.

Dry mouth

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

Diabetes

Your blood glucose levels may be altered by Venlafaxine Retard. Therefore, the doses of your diabetes medicines may need to be adjusted.

Children and adolescents

Venlafaxine Retard should not normally be used in the treatment of children and adolescents under 18 years. In addition, you should know that in patients under 18 years, there is an increased risk of side effects such as suicide attempt, suicidal thoughts and hostility (predominantly aggression, confrontation and irritability) when they take this class of medicines. Despite this, your doctor may prescribe this medicine to patients under 18 years when he decides that it is the best option for the patient. If your doctor has prescribed this medicine to a patient under 18 years and you want to discuss this, 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 are taking Venlafaxine Retard.

Furthermore, the long-term safety of Venlafaxine Retard in relation to growth, maturation, and cognitive and behavioural development in this age group has not been demonstrated.

Taking Venlafaxine Retard Pharma Combix with other medicines

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 Retard with other medicines.

Do not start or stop taking any medicines, including those bought 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 taken with Venlafaxine Retard. Tell your doctor if you have taken any of these medicines within the last 14 days. (MAOIs: see section “What you need to know before taking Venlafaxine Retard”).

• Serotonin Syndrome:

A potentially life-threatening condition or reactions similar to 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 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 tramadol, fentanyl, tapentadol, pethidine or pentazocine (used for severe pain)
• Medicines containing dextromethorphan (used to treat coughs)
• Medicines containing methadone (used for treating addiction to opioids or for treating severe pain)
• Medicines containing methylene blue (used to treat high levels of methaemoglobin in the blood)
• Products containing St John's Wort (also known as Hypericum perforatum, a 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 suspiciousness, 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 heart beat, increased body temperature, rapid changes in blood pressure, overactive reflexes, diarrhoea, 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 heart beat, sweating, severe muscle stiffness, confusion, increased muscle enzymes (determined by a blood test).

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

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 irregular heart beats)
• Antipsychotics such as thioridazine (see also Serotonin Syndrome above)
• Antibiotics such as erythromycin or moxifloxacin (used to treat bacterial infections)
• Antihistamines (used to treat allergies)

The following medicines may also interact with Venlafaxine Retard 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 Retard Pharma Combix with food, drinks and alcohol

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

Do not drink alcohol while taking Venlafaxine Retard Pharma Combix. Taking it with alcohol may cause extreme tiredness and unconsciousness, and may worsen the symptoms of depression and other conditions, such as anxiety disorders.

Pregnancy, breast-feeding and fertility

If you are pregnant or breast-feeding, 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 Retard after discussing the potential benefits and risks with your doctor.

Make sure your midwife and/or doctor knows you are taking Venlafaxine Retard. When taken during pregnancy, similar drugs (SSRIs) may increase the risk of a serious condition in babies, called persistent pulmonary hypertension of the newborn (PPHN), which makes 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, in addition to breathing problems, another symptom your baby may have when born is problems with feeding. 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 Retard Pharma Combix in the final stages of pregnancy, you may have a higher risk of heavy vaginal bleeding after giving birth, especially if you have a history of bleeding disorders. Your doctor or midwife should know that you are taking Venlafaxine Retard Pharma Combix so that they can advise you.

Venlafaxine Retard passes into breast milk. There is a risk of an effect on the baby. Therefore, you should discuss the case with your doctor and he will decide whether you should stop breast-feeding or stop Venlafaxine Retard treatment.

Driving and using machines

Venlafaxine Retard may cause sedation and dizziness. Therefore, you should be informed that if you experience sedation or dizziness, you should avoid potentially hazardous tasks such as driving or using machines.

3. How to take Venlafaxine Retard Pharma Combix

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 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 Retard at approximately the same time each day, either in the morning or in the evening. The capsules should be swallowed whole with liquids and should not be opened, crushed, chewed or dissolved.

Venlafaxine Retard should be taken with food.

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

Do not stop taking this medicine without talking to your doctor (see section “If you stop taking Venlafaxine Retard”).

If you take more Venlafaxine Retard Pharma Combix than you should

In case of overdose or accidental ingestion, contact your doctor or pharmacist immediately or call the Toxicology Information Service, telephone 91 562 04 20, stating the medicine and the amount taken, or go to the casualty department of your nearest hospital.

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

The symptoms of a possible overdose may include rapid heart beat, changes in level of consciousness (ranging from drowsiness to coma), blurred vision, fits or seizures and vomiting.

If you forget to take Venlafaxine Retard Pharma Combix

If you miss a dose, take it as soon as you remember. However, if it is almost 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 Retard that has been prescribed for you in one day.

If you stop taking Venlafaxine Retard Pharma Combix

Do not stop taking your treatment or reduce the dose without the advice of your doctor, even if you feel better. If your doctor thinks that you no longer need Venlafaxine Retard, he may ask you to reduce the dose gradually before stopping treatment altogether. 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 tiredness, dizziness, headache, insomnia, nightmares, dry mouth, loss of appetite, nausea, diarrhoea, nervousness, agitation, confusion, ringing in the ears, tingling or, in rare cases, electric shock sensations, weakness, sweating, fits or flu-like symptoms.

Your doctor will advise you how to stop taking Venlafaxine Retard gradually. If you experience any of these or other symptoms that are troublesome for you, contact your doctor for further advice.

If you have any further questions on 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 Retard Pharma Combix. Tell your doctor immediately, or go to the emergency room 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.

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

• Chest tightness, breathing noise, difficulty swallowing or breathing.
• Severe skin rash, itching or hives (elevated areas of reddened or pale skin that often itch).
• Signs and symptoms of serotonin syndrome that may include agitation, hallucinations, loss of coordination, rapid heart rate, increased body temperature, rapid changes in blood pressure, hyperactive reflexes, diarrhea, coma, nausea and/or 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).

• 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.

Other adverse effects that you should report to your doctorare (the frequency of these adverse effects is included in the list below “other adverse effects that may occur”):

• Cough, breathing noise, difficulty breathing and increased temperature.
• Tarry stools (deposits) or blood in stools.
• 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.
• Nerve problems: such as dizziness, tingling, movement disorder (muscle spasms and stiffness), convulsions or seizures.
• Psychiatric problems, such as hyperactivity and euphoria (unusual feeling of overexcitement).
• Withdrawal effects (see section “How to take Venlafaxine Retard Pharma Combix, if you interrupt treatment with Venlafaxine Retard Pharma Combix”).
• Prolonged bleeding, if you cut or injure yourself, it may take a little longer than usual for the bleeding to stop.

Do not worry if you notice white balls or small granules in your stools after taking this medicine. Inside the capsules of Venlafaxine Retard Pharma Combix, there are spheroids (small white balls) that contain the active ingredient (venlafaxine). These spheroids are released from the capsule in the stomach. As they circulate through the stomach and intestines, venlafaxine is slowly released. The "shell" of the spheroid does not dissolve and is excreted in the stools. Therefore, although you see spheroids in the stools, 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, headache.
• Nausea, dry mouth.
• Excessive sweating (including night sweats).

Common (may affect up to 1 in 10 people)

• Decreased appetite.
• Confusion, feeling strange, lack of orgasm, decreased libido, nervousness, insomnia, abnormal dreams.
• Drowsiness, tremor, 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 urination frequency, 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 (may affect up to 1 in 100 people)

• Hallucinations, feeling detached from reality, agitation, abnormal orgasm (women), lack of feelings or emotions, feeling overexcited, teeth grinding.
• A feeling of restlessness or inability to remain seated or still, fainting, involuntary muscle movements, altered coordination and balance, altered taste perception.
• Rapid heartbeat, feeling dizzy (especially when getting up too quickly).
• Breathing difficulties.
• Vomiting blood, tarry stools (deposits) or blood in stools, which may be a sign of internal bleeding.
• Sensitivity to sunlight, bruising, skin rash, abnormal hair loss.
• Inability to urinate.
• Weight gain or loss.

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

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

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

• 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.
• 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 treatment interruption (see section 2. “What you need to know before taking Venlafaxine Retard Pharma Combix”).
• Disorientation and confusion often accompanied by hallucinations (delirium), aggression.
• Stiffness, spasms and involuntary muscle movements.
• Severe eye pain and reduced or blurred vision.
• Dizziness.
• Decreased blood pressure, abnormal heartbeat, rapid or irregular, which may lead to fainting; unexpected bleeding, for example, bleeding from the gums, blood in urine or vomit, or the appearance of unexpected bruising or broken blood vessels (broken veins).
• Cough, breathing noise, shortness of breath and high temperature, which are symptoms of lung inflammation associated with an increase in white blood cells (pulmonary eosinophilia).
• 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), slight changes in liver enzyme blood levels.
• Itching, mild skin rash.
• Abnormal milk production.
• Heavy vaginal bleeding shortly after childbirth (postpartum hemorrhage), see “Pregnancy, breastfeeding and fertility” in section 2 for more information.

Venlafaxine Retard Pharma Combix sometimes produces unwanted effects that you may not be aware of, such as increased blood pressure or an abnormal heartbeat; slight changes in liver enzyme, sodium or cholesterol blood levels. Less frequently, Venlafaxine Retard Pharma 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 Venlafaxine Retard Pharma 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 Venlafaxine Retard Pharma Combix

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. 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 will help protect the environment.

6. Package contents and additional information

Composition of Venlafaxine Retard Pharma Combix 75 mg

• The active ingredient is venlafaxine. Each prolonged-release capsule contains 84.855 mg of venlafaxine hydrochloride, equivalent to 75 mg of venlafaxine base.
• The other ingredients (excipients) are:
• • Capsule content: microcrystalline cellulose, hydroxypropylcellulose, ethylcellulose, hypromellose, talc.

• Capsule shell: gelatin, red iron oxide (E172), titanium dioxide (E171) and sodium lauryl sulfate.
• • Capsule printing ink: Shellac Lacquer (E904), dehydrated alcohol (E1510), isopropyl alcohol, butyl alcohol, black iron oxide (E172), propylene glycol (E1520), potassium hydroxide (E525) and ammonium hydroxide (E527).

Appearance of the product and package contents

Hard gelatin capsules of size 1, opaque, with body and cap of peach color, with the printing “75 mg” printed in black ink on the body of the capsule. The capsules contain white or off-white microgranules.

Venlafaxine Retard Pharma Combix 75 mg is available in packages of 30 hard capsules, in PVC/PVDC-Aluminum blisters.

Marketing authorization holder

Laboratorios Combix, S.L.U.

C/ Badajoz 2, Edificio 2

28223 Pozuelo de Alarcón (Madrid)

Spain

Manufacturer

Zydus France

ZAC Les Hautes Patures

Parc d'activités des Peupliers

25 Rue des Peupliers

92000 Nanterre

France

or

Centre Spécialités Pharmaceutiques

ZAC des Suzots

35 rue de la Chapelle

63450 Saint Amant Tallende

France

Date of the last revision of this prospectus: 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.