Package Insert: Information for the User

Venlafaxine Extended-Release Tablets 150 mg

Read this entire package insert carefully before taking this medication, as it contains important information for you.

• Keep this package insert, as you may need to refer to it again.
• If you have any questions, consult your doctor or pharmacist.
• This medication has been prescribed for you only and should not be given to others who may have the same symptoms, as it may harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are not listed in this package insert. See section 4.

Contents of the package and additional information

Venlafaxina Retard 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. It is believed 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 increase the levels of serotonin and noradrenaline in the brain.

Venlafaxina 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 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 Venlafaxina Retard Pharma Combix

• If you are allergic to venlafaxine or any of the other ingredients in this medication (listed in section 6).
• If you are also taking or have taken in the last 14 days, any medication known as an irreversible monoamine oxidase inhibitor (IMAO) used to treat depression or Parkinson's disease. Taking an IMAO irreversible with Venlafaxina Retard may produce severe or potentially life-threatening side effects. Additionally, you should wait at least 7 days after stopping Venlafaxina Retard before taking any IMAO (see also the section "Use of other medications" and the information in that section on "Serotonin Syndrome").

Warnings and precautions

Consult your doctor or pharmacist before starting to take Venlafaxina Retard:

• If you are taking other medications that, taken with Venlafaxina Retard, may increase the risk of developing serotonin syndrome (see the section "Taking Venlafaxina Retard with other medications").
• 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 your heart rhythm is altered.
• 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 tendency to develop bleeding or bruising easily (history of bleeding disorders), 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 "Pregnancy, breastfeeding, and fertility").
• If you have a history of mania or bipolar disorder (feeling overexcited or euphoric).
• If you have a history of aggressive behavior.

Venlafaxina Retard may cause restlessness or difficulty sitting or staying still during the first few weeks of treatment. You should consult your doctor if this occurs.

Some medications in the group to which Venlafaxina Retard belongs (called ISRS/IRSN) may cause sexual dysfunction symptoms (see section 4). In some cases, these symptoms persist after stopping treatment.

Do not drink alcohol during treatment with Venlafaxina Retard Pharma Combix, as it may cause extreme fatigue and unconsciousness. Taking it with certain medications and/or alcohol may worsen 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 sometimes have thoughts of harming yourself or committing suicide. This may increase when starting to take antidepressants, as all these medications take time to become effective, usually two weeks but sometimes longer.

You are more likely to experience this:

• If you have previously had thoughts of suicide or self-harm.
• If you are a young adult. Clinical trial information has shown an increased risk of suicidal behavior in young adults (less than 25 years old) with psychiatric disorders treated with antidepressants.

Immediately contact your doctor or go to the nearest hospital emergency room if you have thoughts of harming yourself or committing suicide at any time.

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 tooth decay (caries). Therefore, you should take care of your dental hygiene.

Diabetes

Your blood glucose levels may be altered by Venlafaxina Retard. Therefore, your diabetes medication doses may need to be adjusted.

Children and adolescents

Venlafaxina Retard should not be used normally in the treatment of children and adolescents under 18 years old. Additionally, you should know that in patients under 18 years old, there is a higher risk of adverse effects such as suicidal attempts, suicidal thoughts, and hostility (primarily aggression, confrontational behavior, and irritability) when taking this type of medication. However, the doctor who prescribes this medication may decide to prescribe it to patients under 18 years old when they deem it most suitable for the patient. If the doctor who prescribes this medication to a patient under 18 years old wants to discuss this decision, please return to your doctor. You should inform your doctor if any of the symptoms listed above develop or worsen in these patients under 18 years old who are taking Venlafaxina Retard.

Furthermore, long-term safety in relation to growth, maturation, and cognitive and behavioral development has not been demonstrated.

Taking Venlafaxina Retard Pharma Combix with other medications

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 Venlafaxina Retard with other medications.

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

A potentially life-threatening state, or reactions similar to Neuroleptic Malignant Syndrome (NMS) (see section "Possible side effects") may occur with treatment with venlafaxine, particularly when taken with other medications.

Examples of these medications include:

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.

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

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

Inform your doctor if you are taking medications that may alter your heart rhythm. Some examples of these medications include:

The following medications may interact with Venlafaxina Retard and should be used with caution. It is especially important to mention to your doctor or pharmacist if you are taking medications that contain:

Taking Venlafaxina Retard Pharma Combix with food, drinks, and alcohol

Venlafaxina Retard should be taken with food (see section 3 "How to take Venlafaxina Retard Pharma Combix").

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

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, or think you may be pregnant, consult your doctor or pharmacist before using this medication. You should only take Venlafaxina Retard after discussing the possible benefits and risks for the unborn child with your doctor.

Make sure your midwife and/or doctor know that you are taking Venlafaxina Retard. When taken during pregnancy, similar medications (ISRS) may increase the risk of a severe condition in newborns, called persistent pulmonary hypertension of the newborn (PPHN), causing the baby to breathe faster and turn blue. These symptoms usually start within the first 24 hours after the baby is born. If this happens to your baby, you should immediately contact your midwife and/or doctor.

If you are taking this medication during pregnancy, in addition to breathing problems, another symptom your baby may have when born is feeding difficulties. If your baby has these symptoms when born and you are concerned, contact your doctor and/or midwife, who can advise you.

If you take Venlafaxina Retard Pharma Combix in the final stages of pregnancy, there may be a higher risk of excessive vaginal bleeding after delivery, especially if you have a history of bleeding disorders. Your doctor or midwife should know that you are taking Venlafaxina Retard Pharma Combix so they can advise you.

Venlafaxina 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 they will decide whether you should stop breastfeeding or stop taking this medication.

Driving and operating machinery

Venlafaxina Retard may cause drowsiness and dizziness. Therefore, you should tell patients to avoid performing tasks that may be hazardous, such as driving or operating machinery, if they experience drowsiness or dizziness.

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

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

Take Venlafaxine Retard approximately at the same time every day, either in the morning or at night. The capsules must 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 your dose of this medication may need to be different.

Do not stop taking this medication without consulting your doctor (see section "If you interrupt treatment with Venlafaxine Retard").

If you take more Venlafaxine Retard Pharma Combix than you should

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 or go to the nearest hospital emergency service.

Overdose can put your life at risk, especially with the simultaneous taking of certain medications and/or alcohol (see Taking Venlafaxine Retard Pharma Combix with other medications).

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

If you forgot to take Venlafaxine Retard Pharma Combix

If you have missed 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 Retard that your doctor has prescribed in a day.

If you interrupt the treatment with Venlafaxine Retard Pharma Combix

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 Retard, they may ask you to reduce the dose gradually before stopping 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 fatigue, dizziness, lack of stability, headaches, insomnia, nightmares, dry mouth, loss of appetite, nausea, diarrhea, nervousness, agitation, confusion, ringing in the ears, tingling, or, in rare cases, electric shock sensations, weakness, sweating, seizures, or symptoms similar to the flu.

Your doctor will advise you on how to gradually stop treatment with Venlafaxine Retard. If you experience any of these or other symptoms that bother you, consult your doctor for further advice.

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

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

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

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.

Frequency not known (cannot be estimated from available data)

In its most severe form, serotonin syndrome may resemble Malignant Neuroleptic Syndrome (MNS). The signs and symptoms of MNS may include a combination of fever, rapid heart rate, sweating, severe muscle rigidity, confusion, increased muscle enzymes (determined by blood tests).

Other side effects that you should inform your doctor are (the frequency of these side effects are included in the list below “other side effects that may occur”):

Do not worry if you see white pellets or small granules in your stools after taking this medicine. Inside the capsules of Venlafaxina Retard Pharma Combix, there are spheroids (small white pellets) 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 stool. Therefore, although you may see spheroids in the stool, the dose of the medicine has been absorbed.

Other side effects that may occur

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

Common (may affect up to 1 in 10 people)

Rare (may affect up to 1 in 100 people)

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

Frequency not known (cannot be estimated from available data)

Venlafaxina Retard Pharma Combix may sometimes cause unwanted effects that you may not be aware of, such as increased blood pressure or abnormal heart rate; slight changes in liver enzyme levels, sodium, or cholesterol. Less frequently, Venlafaxina Retard Pharma Combix may reduce the function of platelets in the blood, leading to an increased risk of petechiae or bleeding. Therefore, your doctor may wish to perform occasional blood tests, particularly if you have been taking Venlafaxina Retard Pharma Combix 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 Vigilance 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 medicine.

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

Do not use this medication 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.

Medications should not be disposed of through drains or in the trash. Dispose of packaging and medications you no longer need at the SIGRE collection point at the pharmacy. If in doubt, ask your pharmacist how to dispose of packaging and medications you no longer need. By doing so, you will help protect the environment.

Composition of Venlafaxina Retard Pharma Combix 150 mg

• The active ingredient is venlafaxine. Each prolonged-release capsule contains 169.710 mg of venlafaxine hydrochloride, equivalent to 150 mg of venlafaxine base.
• The other components (excipients) are:
• • Capule content:microcrystalline cellulose, hydroxypropyl cellulose, ethylcellulose, hypromellose, and talc.
  • Capule coating:gelatin, iron oxide red (E172), titanium dioxide (E171), and sodium lauryl sulfate.
  • Capule printing ink:Shellac lacquer (E904), anhydrous ethanol (E1510), isopropyl alcohol, butyl alcohol, iron oxide black (E172), propylene glycol (E1520), potassium hydroxide (E525), and ammonium hydroxide (E527).

Appearance of the product and content of the packaging

Hard gelatin capsules of size 0 EL, opaque, with a red-colored body and cap, with the impression “150 mg” printed in black ink on the body of the capsule. The capsules contain white or off-white microgranules.

Venlafaxina Retard Pharma Combix 150 mg is available in packs of 30 hard capsules, in PVC/PVDC-Aluminum blisters.

Marketing Authorization Holder

Combix, S.L.U.

C/ Badajoz 2, Edificio 2

28223 Pozuelo de Alarcón (Madrid)

Spain

Responsible for manufacturing

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

Last review date of this leaflet: May 2023

Detailed and updated information about this medication is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)http://www.aemps.gob.es.