Venlafaxine prolonged-release Pharma Combix 75 mg hard capsules EFG

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

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

Read the entire leaflet carefully before you start taking 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, ask your doctor or pharmacist.
• This medicine has been prescribed for you only and must not be given to other people, even if they have the same symptoms, as it may harm them.
• If you experience any side effects, talk to your doctor or pharmacist, even if they are side effects not listed in this leaflet. See section 4.

Leaflet contents

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

1. What Venlafaxine Retard Pharma Combix is and what it is 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 believed that people who are depressed and/or suffer from anxiety have lower levels of serotonin and noradrenaline in the brain. How antidepressants work is not fully understood, but they may help increase the levels of serotonin and noradrenaline in the brain.

Venlafaxine Retard is a treatment for depression in adults. It is also a treatment for the following anxiety disorders in adults: generalized anxiety disorder, social anxiety disorder (fear or avoidance of social situations), and panic disorder (panic attacks). Properly treating depressive and anxiety disorders is important to help you feel better. If left untreated, your condition may not resolve or may worsen and become more difficult to treat.

2. What you need to know before taking Venlafaxine Retard Pharma Combix

Do not take Venlafaxine Retard Pharma Combix

• If you are allergic to venlafaxine or to 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 medicine known as an irreversible monoamine oxidase inhibitor (MAOI) used to treat depression or Parkinson’s disease. Taking an irreversible MAOI together with Venlafaxine Retard may cause serious or even potentially fatal adverse effects. In addition, you must wait at least 7 days after stopping Venlafaxine Retard before starting any MAOI (see also the section “Use of other medicines” and the information in that section on “Serotonin Syndrome”).

Warnings and precautions

Talk to your doctor or pharmacist before starting to take Venlafaxine Retard:

• If you are taking other medicines that, when taken together 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 the blood (hyponatremia).
• If you have a tendency to develop bruises or 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, breastfeeding and fertility”).
• If you have a history of, or a family member has had, mania or bipolar disorder (feeling overly excited or euphoric).
• If you have a history of aggressive behavior.

Venlafaxine Retard may cause a feeling of restlessness or an inability to sit or stay still during the first few weeks of treatment. You should consult your doctor if this happens to you.

Some medicines in the group to which Venlafaxine Retard Pharma Combix belongs (called SSRIs/SNRIs) can cause symptoms of sexual dysfunction (see section 4). In some cases, these symptoms persist after stopping treatment.

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

Suicidal thoughts and worsening of your depression or anxiety disorder

If you are depressed and/or have anxiety disorders, you may sometimes have thoughts of harming yourself or of suicide. This risk may increase when you first start taking antidepressants, as all these medicines take time to work—usually about two weeks, but sometimes longer.

This is more likely to happen if:

• You have previously had thoughts of suicide or of harming yourself.
• You are a young adult. Clinical trial data have shown an increased risk of suicidal behavior in young adults (under 25 years of age) with psychiatric illnesses who were treated with antidepressants.

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

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 may also ask them to inform 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 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 of age. In addition, you should know that in patients under 18 years of age, there is an increased risk of adverse effects such as suicide attempts, suicidal thoughts, and hostility (predominantly aggression, confrontational behavior, and irritability) when taking this type of medicine. Nevertheless, your doctor may prescribe this medicine to patients under 18 years of age if they decide it is in the patient’s best interest. If your doctor has prescribed this medicine to a patient under 18 years of age and you wish to discuss this decision, please return to your doctor. You should inform your doctor if any of the symptoms listed above develop or worsen while these patients under 18 years of age are taking Venlafaxine Retard.

In addition, the long-term safety regarding growth, maturation, and cognitive and behavioral development has not been established.

Taking Venlafaxine Retard Pharma Combix with other medicines

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

Your doctor must decide whether you can take Venlafaxine Retard with other medicines.

Do not start taking, or stop taking, any medicine—including those available without a prescription, natural remedies, and herbal medicines—without first checking with your doctor or pharmacist.

• Monoamine oxidase inhibitors (MAOIs) 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 in the last 14 days. (MAOI: see section “What you need to know before taking Venlafaxine Retard”).

• Serotonin syndrome:

A potentially life-threatening condition, or reactions resembling 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 to treat 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 to treat severe pain)
• Medicines containing dextromethorphan (used to treat cough)
• Medicines containing methadone (used for opioid addiction treatment or for treating severe pain)
• Medicines containing methylene blue (used to treat elevated levels of methaemoglobin in the blood)
• 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 an illness with symptoms such as hearing, seeing, or feeling things that are not there, false beliefs, unusual suspiciousness, unclear thinking, and tendency to withdraw)

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). Signs and symptoms of NMS may include a combination of fever, rapid heartbeat, sweating, severe muscle rigidity, confusion, and increased muscle enzymes (determined by a blood test).

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

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

• Antiarrhythmics such as quinidine, amiodarone, sotalol, or dofetilide (used to treat abnormal heart rhythm)
• Antipsychotics such as thioridazine (see also Serotonin Syndrome above)
• Antibiotics such as erythromycin or moxifloxacin (used to treat bacterial infections)
• Antihistamines (used to treat allergy)

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

• Ketoconazole (an antifungal medicine).
• Haloperidol or risperidone (to treat psychiatric conditions).
• Metoprolol (a beta-blocker used to treat 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 during treatment with Venlafaxine Retard Pharma Combix. Taking it together with alcohol may cause extreme tiredness and unconsciousness, and may worsen 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 become pregnant, consult your doctor or pharmacist before using this medicine. You should only take Venlafaxine Retard after discussing with your doctor the possible benefits and possible risks to the unborn child.

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

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

If you take Venlafaxine Retard Pharma Combix in the late 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 be aware that you are taking Venlafaxine Retard Pharma Combix so they can advise you.

Venlafaxine Retard passes into breast milk. There is a risk of effects on the baby. Therefore, you should discuss this with your doctor, who will decide whether you should stop breastfeeding or stop treatment with this medicine.

Driving and using machines

Venlafaxine Retard may cause drowsiness, dizziness. Therefore, patients should be advised that if they experience drowsiness or dizziness, they should avoid performing potentially hazardous tasks such as driving or operating machinery.

3. How to take Venlafaxine Retard Pharma Combix

Follow exactly the instructions for using this medicine as given by your doctor. If you are unsure, consult your doctor or pharmacist again.

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 further, 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 must be swallowed whole with liquid and must not be opened, crushed, chewed, or dissolved.

Venlafaxine Retard should be taken with food.

If you have liver or kidney problems, speak with your doctor, as your dose of this medicine may need to be adjusted.

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

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 at telephone number 91 562 04 20, indicating the medicine and the amount ingested, or go to the nearest hospital emergency department.

Overdose can be life-threatening, especially when taken simultaneously with certain medicines and/or alcohol (see section “Taking Venlafaxine Retard Pharma Combix with other medicines”).

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

If you forget to take Venlafaxine Retard Pharma Combix

If you have missed 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 your next dose as usual. Do not take a double dose to make up for a missed dose. Do not take more than the daily amount of Venlafaxine Retard prescribed for you in one day.

If you stop taking Venlafaxine Retard Pharma Combix

Do not stop taking this medicine or reduce the dose without your doctor’s advice, even if you feel better. If your doctor considers that you no longer need Venlafaxine Retard, they may ask you to gradually reduce the dose before stopping treatment completely. Adverse effects are known to occur when people stop using this medicine, especially if 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 sensations, or, rarely, electric shock-like sensations, weakness, sweating, seizures, or flu-like symptoms.

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

If you have any further questions about the use of this medicine, ask your doctor or pharmacist.

4. Possible adverse effects

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

If any of the following effects occur, stop taking Venlafaxine Retard Pharma Combix and contact your doctor immediately or go to the nearest hospital emergency department:

Uncommon (may affect up to 1 in 100 people)

• Swelling of the face, mouth, tongue, throat, hands or feet and/or swollen itchy rash, difficulty swallowing or breathing.

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

• Chest tightness, noisy breathing, difficulty swallowing or breathing.
• Severe skin rash, itching, or hives (raised red or pale areas of skin that often itch).
• Signs and symptoms of serotonin syndrome, which 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 may resemble Neuroleptic Malignant Syndrome (NMS). Signs and symptoms of NMS may include a combination of fever, rapid heartbeat, sweating, severe muscle rigidity, confusion, and increased muscle enzymes (detected 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 may progress to serious blistering and peeling of the skin.
• Unexplained muscle pain, discomfort, or weakness. This may be a sign of rhabdomyolysis.

Other adverse effects you should report to your doctor are (the frequency of these adverse effects is included in the list below, “Other possible adverse effects”):

• Cough, noisy breathing, difficulty breathing, and increased temperature.
• Tar-like stools or blood in the stool.
• Itching, yellowing of the 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 disorders (muscle spasms and stiffness), seizures or fits.
• Psychiatric problems, such as hyperactivity and euphoria (unusual feeling of excitement).
• Withdrawal effects (see section “How to take Venlafaxine Retard Pharma Combix, if you stop taking Venlafaxine Retard Pharma Combix”).
• Prolonged bleeding—if you cut yourself or sustain a wound, it may take slightly longer than normal for the bleeding to stop.

Do not be concerned if you notice white beads or small granules in your stools after taking this medicine. Inside the capsules of Venlafaxine Retard Pharma Combix there are spheroids (small white beads) containing the active substance (venlafaxine). These spheroids are released from the capsule in the stomach. As they pass through the stomach and intestines, venlafaxine is slowly released. The “shell” of the spheroid does not dissolve and is excreted in the stools. Therefore, even if you see spheroids in your stools, the dose of the medicine has been absorbed.

Other possible adverse effects

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, anorgasmia, decreased libido, restlessness, insomnia, abnormal dreams.
• Drowsiness, tremor, tingling, increased muscle tone.
• Visual disturbances including blurred vision, dilated pupils, inability of the eye to automatically adjust focus from distant to near objects.
• Ringing in the ears (tinnitus).
• Palpitations.
• Increased blood pressure, hot flushes.
• Yawning.
• Vomiting, constipation, diarrhea.
• Increased frequency of urination, difficulty urinating.
• Menstrual irregularities, such as increased bleeding or increased irregular bleeding, abnormal ejaculation/orgasm (in 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 (in women), lack of feelings or emotions, feeling overexcited, teeth grinding.
• A sense of restlessness or inability to sit still or remain still, fainting, involuntary muscle movements, disturbance in coordination and balance, altered taste perception.
• Rapid heartbeat, feeling dizzy (especially when standing up too quickly).
• Difficulty breathing.
• Vomiting blood, tar-like stools (bowel movements), or blood in the stools, which may be a sign of internal bleeding.
• Sun sensitivity, bruising, skin rash, abnormal hair loss.
• Inability to urinate.
• Weight gain or weight loss.

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

• Seizures or fits.
• Inability to control urination.
• Hyperactivity, racing thoughts, and reduced 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, leading to an increased risk of bruising or bleeding.
• Excessive water intake (known as SIADH).
• Decreased sodium levels in the blood.
• Suicidal thoughts and suicidal behaviour—cases of suicidal ideation and behaviour have been reported during treatment with venlafaxine or shortly after discontinuation of treatment (see section 2, “What you need to know before taking Venlafaxine Retard Pharma Combix”).
• Disorientation and confusion, often accompanied by hallucinations (delirium), aggression.
• Muscle rigidity, spasms, and involuntary muscle movements.
• Severe eye pain and reduced or blurred vision.
• Dizziness.
• Decreased blood pressure, abnormal, rapid or irregular heartbeat, which may lead to fainting; unexpected bleeding, for example, bleeding gums, blood in urine or vomit, or the appearance of unexpected bruising or broken blood vessels (broken veins).
• Cough, noisy breathing, 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, yellowing of the eyes or skin, dark urine, flu-like symptoms, which are signs of liver inflammation (hepatitis), mild changes in blood levels of liver enzymes.
• Itching, mild skin rash.
• Abnormal production of breast milk.
• Heavy vaginal bleeding shortly after childbirth (postpartum haemorrhage); see “Pregnancy, breastfeeding and fertility” in section 2 for more information.

Venlafaxine Retard Pharma Combix may sometimes cause unwanted effects that you may not be aware of, such as increases in blood pressure or an abnormal heartbeat; mild changes in blood levels of liver enzymes, sodium, or cholesterol. 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 wish to carry out occasional blood tests, particularly if you have been taking Venlafaxine Retard Pharma Combix for a long time.

Reporting of adverse effects

If you experience any adverse effect, talk to your doctor or pharmacist, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly via the Spanish Pharmacovigilance System for Human Medicines: https://www.notificaram.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Venlafaxine Retard Pharma Combix

Keep this medicine out of sight and reach of children.

Do not use this medicine after the expiry date stated on the packaging. The expiry date refers to the last day of the month indicated.

No special storage conditions are required.

Medicines must not be disposed of via wastewater or household waste. Dispose of empty containers and unused medicines at a SIGRE collection point at your pharmacy. If you are unsure, ask your pharmacist how to properly dispose of containers and unused medicines. This way, you will help protect the environment.

6. Contents of the pack and other information

Composition of Venlafaxine Retard Pharma Combix 75 mg

• The active substance is venlafaxine. Each prolonged-release capsule contains 84.855 mg of venlafaxine hydrochloride, equivalent to 75 mg of venlafaxine base.

• The other components (excipients) are:

  • Capsule contents: microcrystalline cellulose, hydroxypropylcellulose, ethylcellulose, hypromellose, talc.

• Capsule shell: gelatin, iron oxide red (E172), titanium dioxide (E171), and sodium lauryl sulfate.

  • Printing ink for the capsule: 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 contents of the pack

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

Venlafaxine Retard Pharma Combix 75 mg is available in packs 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 most recent revision of this leaflet: May 2023

Detailed and up-to-date information on this medicinal product is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es.