PREFAXINE 37.5 mg Capsules

Contents of the leaflet

1. Package Leaflet: Information for the Patient
   1. Prefaxine, 75 mg, prolonged-release, hard capsules
   2. Prefaxine, 150 mg, prolonged-release, hard capsules
   3. It is very important that you read the leaflet carefully before taking your medicine. It contains important information for you.
   4. Contents of the pack
2. What Prefaxine is and what it is used for
3. Before you take Prefaxine
   1. When not to take Prefaxine:
   2. Warnings and precautions
   3. Children and adolescents
   4. Prefaxine with other medicines
   5. In case of suspected serotonin syndrome, you should immediately tell your doctor or go to the nearest hospital.
   6. Prefaxine with food, drink, and alcohol
   7. Pregnancy and breastfeeding
   8. Driving and using machines
4. How to take Prefaxine
   1. What to do if you take more Prefaxine than you should
   2. What to do if you forget to take Prefaxine
   3. Stopping Prefaxine treatment
5. Possible side effects
   1. Allergic reactions
   2. Full list of side effects
   3. Very common (affects more than 1 in 10 people)
   4. Common (affects 1 to 10 people in 100)
   5. Uncommon (affects 1 to 10 people in 1,000)
   6. Rare (affects 1 to 10 people in 10,000)
   7. Frequency not known (cannot be estimated from the available data)
   8. Reporting side effects
6. How to store Prefaxine
7. Contents of the pack and other information
   1. What Prefaxine contains
   2. What Prefaxine looks like and contents of the pack
   3. Marketing authorization holder and manufacturer
   4. Date of last revision of the leaflet

Package Leaflet: Information for the Patient

Prefaxine, 37.5 mg, prolonged-release, hard capsules

Prefaxine, 75 mg, prolonged-release, hard capsules

Prefaxine, 150 mg, prolonged-release, hard capsules

Venlafaxine

It is very important that you read the leaflet carefully before taking your medicine. It contains important information for you.

• You should 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. Do not pass it on to others. It may harm them, even if their symptoms 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. See section 4.

Contents of the pack

• 1. What Prefaxine is and what it is used for
• 2. Before you take Prefaxine
• 3. How to take Prefaxine
• 4. Possible side effects
• 5. How to store Prefaxine
• 6. Contents of the pack and other information

1. What Prefaxine is and what it is used for

Prefaxine is an antidepressant that belongs to a group of medicines called serotonin and norepinephrine reuptake inhibitors (SNRIs). These medicines are used in the treatment of depression and other conditions, such as anxiety disorders. It is thought that people who are depressed and/or anxious have lower levels of certain substances in the brain, such as serotonin and norepinephrine. Although the exact mechanism of action is unknown, Prefaxine may help by increasing the levels of these substances in the brain.

Prefaxine is used to treat depression in adults. Prefaxine is also used to treat generalized anxiety disorder, social anxiety disorder (fear or avoidance of social situations), and panic disorder (panic attacks) in adults. For patients to feel better, it is essential that depression and anxiety disorders are treated properly. If left untreated, the condition may not improve, may worsen, and become more difficult to treat.

2. Before you take Prefaxine

When not to take Prefaxine:

• if you are allergic to venlafaxine or any of the other ingredients of this medicine (listed in section 6);
• if you are taking, or have taken within the last 14 days, any medicines known as irreversible monoamine oxidase inhibitors (MAOIs) which are used to treat depression or Parkinson's disease. Taking MAOIs with Prefaxine may cause serious or even life-threatening side effects. Also, before starting treatment with MAOIs, you should wait at least 7 days after stopping Prefaxine treatment (see also the section "Taking other medicines").

Before starting treatment with Prefaxine, tell your doctor or pharmacist if you are taking any other medicines, including those obtained without a prescription, herbal or complementary medicines, or St. John's Wort (Hypericum perforatum).

Warnings and precautions

Before taking Prefaxine, tell your doctor or pharmacist if:

• you are taking other medicines that may increase the risk of serotonin syndrome (see section "Taking other medicines");
• you have eye problems, such as certain types of glaucoma (increased pressure in the eye);
• you have had high blood pressure in the past;
• you have had heart problems in the past;
• you have had irregular heart rhythms in the past;
• you have had seizures (epilepsy) in the past;
• you have had low sodium levels in the blood (hyponatremia) in the past;
• you have a tendency to bruise or bleed easily, or if you are taking other medicines that may increase the risk of bleeding, such as warfarin (used to prevent blood clots), or if you are pregnant (see section "Pregnancy and breastfeeding");
• you have high cholesterol levels;
• you or a family member have had mania or bipolar disorder (excessive excitement or euphoria) in the past;
• you have had aggressive behavior in the past.

Prefaxine may cause feelings of anxiety or inability to sit or stand still. If such symptoms occur, you should inform your doctor.

Medicines like Prefaxine (SSRIs or SNRIs) may cause sexual dysfunction (see section 4). In some cases, these symptoms have persisted after stopping treatment.

You should discuss this with your doctor before starting treatment with Prefaxine if any of the above applies to you.

Suicidal thoughts and worsening of depression or anxiety

Patients with depression and/or anxiety may sometimes think about harming themselves or committing suicide. Such thoughts or behavior may worsen when first taking antidepressants, as these medicines start to work usually after 2 weeks, sometimes later.

Suicidal thoughts or behavior are more likely if:

• you have had suicidal thoughts or self-harm in the past;
• you are a young adult. Data from clinical trials have shown an increased risk of suicidal behavior in adults aged less than 25 years with psychiatric conditions who were treated with an antidepressant.

If you have thoughts of harming yourself or committing suicide, contact your doctor or go to the nearest hospital immediately.

It may be helpful to tell relatives or friends that you are depressed or anxious and ask them to read this leaflet. You may want to 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 is reported by 10% of patients treated with venlafaxine. This may increase the risk of tooth decay. Therefore, pay special attention to oral hygiene.

Diabetes

Prefaxine may affect blood sugar levels. Therefore, it may be necessary to adjust the dosage of antidiabetic medicines.

Effect on urine screening tests

There have been reports of false-positive results in immunological tests for phencyclidine (PCP) and amphetamine in urine in patients taking venlafaxine.

Children and adolescents

Prefaxine should not be used in children and adolescents under 18 years of age. It is also important to note that patients under 18 years of age who take medicines of this class are at increased risk of side effects, such as suicide attempts, suicidal thoughts, and hostility (especially aggression, rebelliousness, and anger). However, your doctor may prescribe this medicine for patients under 18 years of age if they think it is in their best interest. If your doctor has prescribed this medicine for a patient under 18 years of age, and you have any concerns, you should discuss them with your doctor. You should tell your doctor if any of the above symptoms occur or worsen in patients under 18 years of age taking Prefaxine.

Long-term safety data on growth, maturation, and cognitive and behavioral development in this age group are not available.

Prefaxine with other medicines

Tell your doctor or pharmacist about all the medicines you are taking now or have taken recently, and about any medicines you plan to take.

Your doctor will decide whether you can take Prefaxine with other medicines.

Do not start or stop taking any other medicines, including those obtained without a prescription, herbal or complementary medicines, or St. John's Wort (Hypericum perforatum), without talking to your doctor or pharmacist first.

• Monoamine oxidase inhibitors, used to treat depression or Parkinson's disease, should not be taken with Prefaxine. Tell your doctor if you have taken these medicines within the last 14 days (MAOIs; see section 2 "Before taking Prefaxine");
• Serotonin syndrome: During treatment with venlafaxine, a potentially life-threatening condition called serotonin syndrome may occur (see section 4 "Possible side effects"), especially when taken with other medicines, such as:
• triptans (used to treat migraine headaches);
• medicines used to treat depression, such as selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants, or lithium;
• medicines containing the antibiotic linezolid (used to treat infections);
• medicines containing the reversible MAOI moclobemide (used to treat depression);
• medicines containing sibutramine (used for weight loss);
• medicines containing tramadol, fentanyl, tapentadol, pethidine, pentazocine, or buprenorphine (used to treat severe pain);
• medicines containing dextromethorphan (used to treat cough);
• medicines containing methadone (used to treat opioid addiction or severe pain);
• medicines containing methylene blue (used to treat high levels of methemoglobin in the blood);
• medicines containing St. John's Wort (Hypericum perforatum) - herbal or complementary medicines used to treat mild depression;
• medicines containing tryptophan (used to treat sleep disorders and depression);
• antipsychotic medicines (used to treat conditions with symptoms such as hearing, seeing, or feeling things that are not there, delusions, unnatural suspicion, unclear thinking, and withdrawal).

Symptoms of serotonin syndrome may include restlessness, hallucinations, loss of coordination, rapid heart rate, high body temperature, rapid changes in blood pressure, overreactivity, diarrhea, coma, nausea, vomiting.

The most severe form of serotonin syndrome can resemble a life-threatening condition called neuroleptic malignant syndrome. Its symptoms include fever, rapid heart rate, sweating, muscle stiffness, confusion, increased levels of muscle enzymes in the blood (detected in blood tests).

In case of suspected serotonin syndrome, you should immediately tell your doctor or go to the nearest hospital.

If you are taking medicines that may affect your heart rhythm, you should tell your doctor. Examples of such medicines are:

• anti-arrhythmic medicines, such as quinidine, amiodarone, sotalol, or dofetilide (used to treat irregular heart rhythms).
• antipsychotic medicines, such as thioridazine (see above - serotonin syndrome).
• antibiotics, such as erythromycin or moxifloxacin (used to treat bacterial infections).
• antihistamines (used to treat allergies).

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

• ketoconazole (an antifungal medicine);
• haloperidol or risperidone (medicines used to treat mental disorders);
• metoprolol (a beta-blocker used to treat high blood pressure and heart disease);
• oral contraceptives.

Prefaxine with food, drink, and alcohol

Prefaxine should be taken with food (see section 3 "How to take Prefaxine").

You should not drink alcohol while taking Prefaxine.

Pregnancy and breastfeeding

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.

Prefaxine should only be used during pregnancy if the potential benefits outweigh the potential risks to the unborn child.

You should inform your doctor and/or midwife that you are taking Prefaxine. Taking Prefaxine or similar medicines during pregnancy may increase the risk of a serious condition in the newborn called persistent pulmonary hypertension of the newborn (PPHN). This condition is characterized by rapid breathing and bluish discoloration. Symptoms usually appear within 24 hours of birth. If such symptoms occur in the newborn, you should contact your doctor and/or midwife immediately.

If you take Prefaxine during pregnancy, the following symptoms may occur in the baby after birth: poor feeding and breathing difficulties. If you are concerned about such symptoms after birth, you should contact your doctor and/or midwife, who will be able to provide appropriate advice.

Taking Prefaxine towards the end of pregnancy may increase the risk of severe bleeding from the vagina, occurring shortly after delivery, especially if you have a history of bleeding disorders. If you take Prefaxine, you should inform your doctor or midwife so that they can provide you with appropriate advice.

Prefaxine passes into breast milk. There is a risk of an effect on the baby. You should discuss this with your doctor, who will decide whether you should stop breastfeeding or stop Prefaxine treatment.

Driving and using machines

You should not drive or operate machinery until you know how Prefaxine affects you.

This medicine contains less than 1 mmol (23 mg) of sodium per capsule, which is essentially "sodium-free".

3. How to take Prefaxine

Always take this medicine exactly as your doctor or pharmacist has told you. If you are not sure, check with your doctor or pharmacist.

The usual recommended starting dose is 75 mg per day for the treatment of depression and social anxiety disorder.

This dose may be gradually increased by your doctor if necessary, up to a maximum dose of 375 mg per day for the treatment of depression. The maximum dose for the treatment of social anxiety disorder is 225 mg per day.

Prefaxine should be taken once daily, at approximately the same time, regardless of whether the medicine is taken in the morning or evening. The capsules should be swallowed whole with a drink of water. They should not be opened, crushed, chewed, or dissolved.

Prefaxine should be taken with food.

You should inform your doctor if you have liver or kidney problems, as you may need a dose adjustment.

Do not stop taking Prefaxine without talking to your doctor (see section "Stopping Prefaxine treatment").

What to do if you take more Prefaxine than you should

If you have taken more Prefaxine than you should, contact your doctor immediately.

Symptoms of possible overdose may include rapid heart rate, changes in consciousness (from drowsiness to coma), changes in vision, seizures, and vomiting.

What to do if you forget to take Prefaxine

If you forget to take 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 at the usual time. Do not take more than one dose in a day.

Stopping Prefaxine treatment

Do not stop taking Prefaxine without talking to your doctor first, even if you feel better. If your doctor thinks it is necessary, they will tell you how to gradually reduce the dose before stopping treatment completely. When stopping Prefaxine treatment, especially if it is stopped abruptly or the dose is reduced too quickly, you may experience side effects such as feeling tired, dizziness, feeling empty-headed, headache, insomnia, vivid dreams, dry mouth, loss of appetite, nausea, diarrhea, nervousness, anxiety, confusion, ringing in the ears, tingling or numbness, weakness, sweating, seizures, or flu-like symptoms.

Your doctor will tell you how to gradually stop taking Prefaxine. If you experience any of the above symptoms or other symptoms that are troublesome to you, you should talk to your doctor.

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

4. Possible side effects

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

Allergic reactions

If you experience any of the following side effects, stop taking Prefaxine and contact your doctor or go to the nearest hospital immediately:

• chest pain, wheezing, difficulty swallowing or breathing;
• swelling of the face, throat, hands, or feet;
• feeling anxious or nervous, dizziness, palpitations, sudden flushing, or feeling warm;
• severe rash, itching, hives (red or pale raised patches on the skin, often itchy);
• symptoms of serotonin syndrome: restlessness, hallucinations, loss of coordination, rapid heart rate, high body temperature, rapid changes in blood pressure, overreactivity, diarrhea, coma, nausea, vomiting. The most severe form of serotonin syndrome can resemble a life-threatening condition called neuroleptic malignant syndrome. Its symptoms include fever, rapid heart rate, sweating, muscle stiffness, confusion, increased levels of muscle enzymes in the blood (detected in blood tests).

If you experience any of the following side effects, you should contact your doctor:

• cough, wheezing, shortness of breath, and high fever;
• black (tar-like) stools or blood in stools;
• yellowing of the skin or whites of the eyes, itching, dark urine, which may be signs of liver inflammation;
• heart problems, such as rapid or irregular heart rate, high blood pressure;
• vision problems, such as blurred vision, dilated pupils;
• nervous system problems, such as dizziness, tingling, coordination problems, seizures, or convulsions;
• psychiatric problems, such as excessive restlessness and euphoria (feeling unusually excited);
• withdrawal symptoms (see sections "How to take Prefaxine" and "Stopping Prefaxine treatment");
• prolonged bleeding time - in case of injury, the bleeding time may be slightly longer than usual.

Full list of side effects

Very common (affects more than 1 in 10 people)

• dizziness, headache;
• nausea, dry mouth;
• sweating (including night sweats).

Common (affects 1 to 10 people in 100)

• decreased appetite;
• disorientation; feeling detached from oneself; lack of orgasm; decreased libido; nervousness; insomnia; vivid dreams;
• drowsiness; tremors; tingling; increased muscle tone;
• vision problems, including blurred vision; dilated pupils; inability of the eye to accommodate (automatic change in focus from distant to near objects);
• ringing in the ears (tinnitus);
• palpitations;
• increased blood pressure; flushing;
• yawning;
• vomiting; constipation; diarrhea;
• increased frequency of urination; problems with urination;
• abnormal menstrual bleeding, such as heavy or irregular bleeding; ejaculation or orgasm disorders (men); erectile dysfunction (impotence);
• weakness (asthenia); fatigue;
• increased cholesterol levels in the blood.

Uncommon (affects 1 to 10 people in 1,000)

• hallucinations; feeling detached from reality; agitation; orgasm disorders (women); apathy; feeling excessively excited; teeth grinding;
• feeling anxious or unable to sit or stand still; fainting; uncontrolled movements; coordination problems; taste disorders;
• rapid heart rate; dizziness (especially when standing up too quickly);
• shortness of breath;
• vomiting blood; black (tar-like) stools or blood in stools, which may be signs of internal bleeding;
• generalized swelling of the skin, especially of the face, lips, tongue, throat, or hands and feet, and/or a raised, itchy rash (hives); sensitivity to light; bruising; rash; excessive hair loss;
• urinary retention;
• weight gain; weight loss.

Rare (affects 1 to 10 people in 10,000)

• seizures;
• urinary incontinence;
• excessive excitement, racing thoughts, and decreased need for sleep (mania).

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

• decreased platelet count, which may increase the risk of bruising or bleeding; blood disorders that may increase the risk of infection;
• severe vaginal bleeding after delivery (postpartum hemorrhage), see additional information in section "Pregnancy and breastfeeding";
• swelling of the face or tongue, difficulty breathing or swallowing, often with a rash (may indicate a severe allergic reaction);
• syndrome of inappropriate antidiuretic hormone secretion (SIADH);
• low sodium levels in the blood;
• suicidal thoughts and behaviors; suicidal thoughts and behaviors have been reported during venlafaxine treatment or soon after stopping treatment (see section 2 "Before taking Prefaxine");
• confusion with frequent hallucinations (delirium); aggressive behavior;
• high fever with muscle stiffness, confusion, or agitation, and sweating or uncontrolled muscle movements, which may be symptoms of a life-threatening condition called neuroleptic malignant syndrome; feeling excited, drowsiness, persistent rapid eye movements, clumsiness, anxiety, feeling drunk, sweating, or muscle stiffness, which are symptoms of serotonin syndrome; muscle stiffness, spasms, and uncontrolled muscle movements;
• severe eye pain and vision problems or blurred vision;
• dizziness;
• low blood pressure; abnormal or rapid heart rate, which may cause fainting; unexpected bleeding, e.g., bleeding from the gums, blood in urine or vomit, or unexpected appearance of bruises or broken blood vessels (broken veins);
• cough, wheezing, shortness of breath, and high fever, which may be symptoms of pneumonia associated with an increased number of white blood cells in the blood (eosinophilic pneumonia);
• severe abdominal or back pain (which may indicate serious intestinal, liver, or pancreatic problems);
• itching, yellowing of the skin or whites of the eyes; dark urine, which may be symptoms of liver inflammation; flu-like symptoms;
• skin rash that may lead to blistering and peeling; itching; mild rash;
• unexplained muscle pain, tenderness, or weakness (rhabdomyolysis);
• abnormal milk production in women.

Prefaxine may also cause side effects that you are not aware of, such as increased blood pressure or abnormal heart rhythm, minor changes in liver enzyme levels, sodium, or cholesterol levels in the blood. In rare cases, Prefaxine may affect platelet function, leading to an increased risk of bruising or bleeding. Therefore, your doctor may recommend blood tests from time to time, especially during long-term treatment with Prefaxine.

Reporting side effects

If you experience any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in the "Further information" section.

5. How to store Prefaxine

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

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

The packaging label carries a "use by" date and a batch number.

Do not store above 30°C.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Prefaxine contains

• The active substance is venlafaxine. Each prolonged-release, hard capsule contains 37.5 mg, 75 mg, or 150 mg of venlafaxine (as venlafaxine hydrochloride).
• The other ingredients are: 37.5 mg prolonged-release, hard capsules: capsule contents: hypromellose, ammonio methacrylate copolymer (type B), sodium lauryl sulfate, magnesium stearate; capsule shell: methacrylic acid - ethyl acrylate copolymer (1:1) dispersion 30 per cent; capsule shell: gelatin, titanium dioxide (E171); ink: shellac, iron oxide black (E172), propylene glycol (E1520).

75 mg prolonged-release, hard capsules: capsule contents: hypromellose, ammonio methacrylate copolymer (type B), sodium lauryl sulfate, magnesium stearate; capsule shell: methacrylic acid - ethyl acrylate copolymer (1:1) dispersion 30 per cent; capsule shell: gelatin, titanium dioxide (E171), iron oxide red (E172); ink: shellac, iron oxide black (E172), propylene glycol (E1520).

150 mg prolonged-release, hard capsules: capsule contents: hypromellose, ammonio methacrylate copolymer (type B), sodium lauryl sulfate, magnesium stearate; capsule shell: methacrylic acid - ethyl acrylate copolymer (1:1) dispersion 30 per cent; capsule shell: gelatin, titanium dioxide (E171), erythrosine (E127), indigo carmine (E132); ink: shellac, iron oxide black (E172), propylene glycol (E1520).

What Prefaxine looks like and contents of the pack

37.5 mg prolonged-release, hard capsules: white, opaque, hard gelatin capsules (size 0) with "VEN" printed on the cap and "37.5" on the body, containing one round, biconvex, coated tablet.

75 mg prolonged-release, hard capsules: peach, opaque, hard gelatin capsules (size 0) with "VEN" printed on the cap and "75" on the body, containing two round, biconvex, coated tablets.

150 mg prolonged-release, hard capsules: scarlet, opaque, hard gelatin capsules (size 00) with "VEN" printed on the cap and "150" on the body, containing three round, biconvex, coated tablets.

The pack contains 28 prolonged-release, hard capsules.

Marketing authorization holder and manufacturer

Zakłady Farmaceutyczne POLPHARMA S.A.

ul. Pelplińska 19, 83-200 Starogard Gdański

tel. + 48 22 364 61 01

Date of last revision of the leaflet