Package leaflet: Information for the patient

Prefaxine, 37.5 mg, prolonged-release capsules, hard
Prefaxine, 75 mg, prolonged-release capsules, hard
Prefaxine, 150 mg, prolonged-release capsules, hard
Venlafaxine
Please read this leaflet carefully before taking this medicine, as it contains important information for you.

Keep this leaflet for future reference.
If you have any questions, please consult your doctor or pharmacist.
This medicine has been prescribed for a specific individual. Do not pass it on to others. This medicine may harm someone else, even if their symptoms are the same.
If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Table of contents of the leaflet

What Prefaxine is and what it is used for
Important information before taking Prefaxine
How to take Prefaxine
Possible side effects
How to store Prefaxine
Contents of the pack and other information

1. What Prefaxine is and what it is used for

Prefaxine is an antidepressant medicine belonging to a group of medicines called serotonin and noradrenaline reuptake inhibitors (SNRIs). Medicines in this group are used in the treatment of depression and other conditions such as anxiety disorders. It is believed that people experiencing depression and/or anxiety 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 by increasing the levels of serotonin and noradrenaline in the brain.
Prefaxine is used in the treatment of depression in adults. Prefaxine is also indicated for the treatment of the following anxiety disorders in adults: generalized anxiety disorder, social phobia (fear or avoidance of social situations), and panic disorder (panic attacks). For the patient to feel better, it is important that treatment for depression and anxiety disorders is properly managed. If treatment is not initiated, the condition may not improve, may worsen, and may become significantly more difficult to treat.

2. Important information before using Prefaxine

When not to use Prefaxine:

if the patient is allergic to venlafaxine or to any of the other ingredients of this medicine (listed in section 6);
if the patient is currently taking or has taken within the last 14 days any medicine from the group of irreversible monoamine oxidase inhibitors (MAOIs) used to treat depression or Parkinson's disease. Taking irreversible MAOIs together with other medicines, including Prefaxine, may cause severe or even life-threatening adverse reactions. Also, before starting any medicine from the MAOI group, the patient should wait at least 7 days after stopping treatment with Prefaxine (see also section "Prefaxine with other medicines", including "Serotonin syndrome").

Warnings and precautions

Before starting treatment with Prefaxine, discuss the following with your doctor or pharmacist:

if the patient is taking other medicines, such as buprenorphine (an opioid medicine used to treat acute or chronic pain), which, when taken together with Prefaxine, may increase the risk of serotonin syndrome (see section "Prefaxine with other medicines");
if the patient has eye disorders, such as certain types of glaucoma (increased pressure in the eyeball);
if the patient has previously had high blood pressure;
if the patient has previously had heart diseases;
if the patient has previously had cardiac arrhythmias;
if the patient has previously had seizures (epilepsy);
if the patient has previously had low sodium levels in the blood (hyponatraemia);
if the patient has a tendency to bruise or bleed (bleeding disorders in the past), or if the patient is taking other medicines that may increase the risk of bleeding, e.g. warfarin (used as an anticoagulant), or if the patient is pregnant (see section "Pregnancy and breastfeeding");
in case of high cholesterol levels;
if the patient or anyone in their family has previously experienced mania or bipolar disorder (feelings of excessive excitement or euphoria);
if the patient has previously exhibited aggressive behaviour.

Prefaxine may cause feelings of restlessness or an inability to sit still or remain motionless.
If such symptoms occur, inform your doctor immediately.
Medicines such as Prefaxine (so-called SSRIs or SNRIs) may cause sexual dysfunction (see section 4). In some cases, these symptoms persisted after discontinuation of treatment.
Consult your doctor before starting treatment with Prefaxine if any of the above conditions apply to the patient.

Do not consume alcohol during treatment with Prefaxine, as this may cause extreme fatigue and loss of consciousness. Concurrent use with alcohol and (or) certain medicines may worsen symptoms of depression and other medical conditions, such as anxiety disorders.

Suicidal thoughts and worsening of depression or anxiety disorders

Patients with depression and (or) anxiety disorders may sometimes think about self-harm or suicide. These symptoms or behaviours may worsen at the beginning of treatment with antidepressants, as these medicines usually start to work after about 2 weeks, sometimes later.

The occurrence of suicidal thoughts, thoughts of self-harm or suicide is more likely if:

the patient has previously experienced suicidal thoughts or self-harm;
the patient is a young adult; clinical trial data indicate an increased risk of suicidal behaviour in individuals under 25 years of age with psychiatric disorders who were treated with antidepressants.

If the patient experiences suicidal thoughts or thoughts of self-harm, contact a doctor immediately or go to the nearest hospital.

It may be helpful to inform family members or friends about the depression or anxiety disorder and ask them to read this leaflet. The patient may ask for help from relatives or friends and request them to inform the patient if they notice worsening depression or anxiety, or concerning changes in behaviour.

Dry mouth

Dry mouth is reported by 10% of patients treated with venlafaxine. This may increase the risk of dental caries. Therefore, special attention should be paid to oral hygiene.

Diabetes

Prefaxine may alter blood glucose levels. Therefore, dosage adjustments of antidiabetic medicines may be necessary.

Effect on urine screening tests

In patients taking venlafaxine, false-positive results in immunological urine screening tests for phencyclidine and amphetamine have been reported.

Children and adolescents

Prefaxine should not be used in children and adolescents under 18 years of age. It should also be emphasized that patients under 18 years of age who take medicines from this group are at increased risk of adverse reactions such as suicide attempts, suicidal thoughts, and hostility (particularly aggression, defiant behaviour, and anger). Nevertheless, a doctor may prescribe this medicine to patients under 18 years of age if they consider it beneficial. If a doctor has prescribed this medicine to a patient under 18 years of age, consult the doctor again in case of any doubts. Inform the doctor if any of the above symptoms occur or worsen in patients under 18 years of age taking Prefaxine.

Long-term safety regarding effects on growth, maturation, and cognitive and behavioural development in this age group has not yet been established.

Prefaxine with other medicines

Tell your doctor or pharmacist about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to take.

The treating doctor will decide whether Prefaxine can be used together with other medicines.

Do not start or stop taking any other medicines, including over-the-counter medicines, natural or herbal remedies, without first consulting your doctor or pharmacist.

Monoamine oxidase inhibitors (MAOIs) used to treat depression or Parkinson's disease must not be taken with Prefaxine. Inform your doctor if you have taken these medicines within the last 14 days (MAOIs; see section 2. "Important information before using Prefaxine");
Serotonin syndrome: During treatment with venlafaxine, a potentially life-threatening condition (see section 4. "Possible side effects"), known as serotonin syndrome, may occur, especially when used concomitantly with medicines such as:
- triptans (used for migraine headaches);
- medicines used to treat depression, e.g. selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants, or medicines containing 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 methemoglobin levels in the blood);
medicines containing St. John's wort (Hypericum perforatum) – natural or herbal remedies used to treat mild depression;
medicines containing tryptophan (used for sleep disorders and depression);
antipsychotics (used to treat illnesses with symptoms such as hearing, seeing, and feeling things that are not real, delusions, unnatural suspicion, unclear thinking, social withdrawal).

Subjective and objective symptoms of serotonin syndrome may include: agitation, hallucinations, loss of coordination, rapid heartbeat, elevated body temperature, rapid changes in blood pressure, hyperreflexia, diarrhoea, coma, nausea, vomiting.

The most severe form of serotonin syndrome may resemble neuroleptic malignant syndrome. Its subjective and objective symptoms include: fever, increased heart rate, sweating, muscle rigidity, confusion, and elevated muscle enzyme levels (detected in blood tests).

If serotonin syndrome is suspected, inform your doctor immediately or go to the nearest hospital emergency department.

If the patient is taking medicines that may affect heart rhythm, inform the doctor. Examples of such medicines:

antiarrhythmics, such as quinidine, amiodarone, sotalol, or dofetilide (used to treat cardiac arrhythmias);
antipsychotics, 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 therefore be used with caution. It is particularly important to inform the doctor if the patient is taking medicines containing:

ketoconazole (an antifungal medicine);
haloperidol or risperidone (medicines used to treat psychiatric disorders);
metoprolol (a beta-blocker used to treat hypertension and heart diseases);
oral contraceptives.

Prefaxine with food, drink and alcohol

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

Do not consume alcohol during treatment with Prefaxine. Concurrent use with alcohol may cause extreme fatigue and loss of consciousness and may worsen symptoms of depression and other medical conditions, such as anxiety disorders.

Pregnancy and breastfeeding

If the patient is pregnant or breastfeeding, suspects she may be pregnant, or plans to become pregnant, she should consult her doctor or pharmacist before using this medicine.

Prefaxine should only be used after discussing with a doctor the potential benefits and possible risks to the unborn child.

Inform your doctor and (or) midwife about taking Prefaxine. Taking medicines with similar action (SSRIs) 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 cyanosis. Symptoms usually appear within 24 hours after birth. If such symptoms occur in the newborn, contact a doctor and (or) midwife immediately.

If the patient takes this medicine during pregnancy, the following symptoms may occur in the newborn after birth: feeding difficulties and breathing problems. If the patient is concerned about such symptoms in the newborn after birth, contact a doctor and (or) midwife, who will be able to provide appropriate advice.

Taking Prefaxine near the end of pregnancy may increase the risk of severe vaginal bleeding shortly after delivery, especially if the patient has a history of blood clotting disorders. If the patient is taking Prefaxine, she should inform her doctor or midwife so they can provide appropriate advice.

Prefaxine passes into breast milk. There is a risk of effects on the infant. Therefore, discuss this issue with your doctor, who will decide whether to discontinue breastfeeding or stop treatment with Prefaxine.

Driving and operating machinery

Do not drive or operate machinery until you know how this medicine affects you.

This medicine contains less than 1 mmol (23 mg) of sodium per capsule, i.e. the medicine is considered "sodium-free".

3. How to use Prefaxine

This medicine should always be taken as directed by your doctor or pharmacist. If in
doubt, consult your doctor or pharmacist.
The usual recommended starting dose for the treatment of depression and social phobia is 75 mg per day.
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 phobia is 225 mg per day.
Prefaxine should be taken every day at approximately the same time, regardless of whether it is taken in the morning or evening. The capsules should be swallowed whole with liquid.
Do not open, crush, chew, or dissolve the capsules.
Prefaxine should be taken with food.
Inform your doctor if you have any liver or kidney diseases, as your dose may need to be adjusted.
Do not stop taking Prefaxine without consulting your doctor (see section “Stopping Prefaxine”).
Taking more than the recommended dose of Prefaxine
If you take more than the recommended dose of Prefaxine, contact your doctor immediately.
Overdose may be life-threatening, especially when taken with alcohol and/or certain other medicines (see section “Prefaxine with other medicines”).
Symptoms of overdose may include: rapid heartbeat, disturbances in consciousness (from drowsiness to coma), vision disturbances, seizures, and vomiting.
Missing a dose of Prefaxine
If you miss a dose, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and take only your next dose at the regular time. Do not take a double dose within the same day to make up for a missed dose. Do not exceed the daily dose of Prefaxine prescribed by your doctor.
Stopping Prefaxine treatment
Do not stop treatment or reduce the dose of Prefaxine without consulting your doctor, even if you feel better. If your doctor decides that you can discontinue Prefaxine, they will advise you on how to gradually reduce the dose before stopping treatment completely.
Patients discontinuing Prefaxine, especially those who stop treatment abruptly or reduce the dose too quickly, may experience adverse effects such as fatigue, dizziness, feeling of emptiness in the head, headache, insomnia, nightmares, dry mouth, loss of appetite, nausea, diarrhea, nervousness, agitation, disorientation, ringing in the ears, tingling or numbness, weakness, sweating, seizures, or flu-like symptoms.
Your doctor will advise you on how to gradually discontinue Prefaxine. If any of the symptoms listed above, or other bothersome symptoms, occur, consult your doctor.
If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse reactions

Like any medicine, this medicine can cause adverse reactions, although not everyone experiences them.

Allergic reactions
If any of the following adverse reactions occur, discontinue Prefaxine immediately and contact a doctor or go to the emergency room of the nearest hospital without delay:

chest tightness, wheezing, difficulty swallowing or breathing;
swelling of the face, throat, hands or feet;
feeling nervous or agitated, dizziness, sensation of pounding heartbeat, sudden flushing of the skin and/or feeling hot;
severe rash, itching, urticaria (swelling with red or pale discoloration, often accompanied by itching);
symptoms of serotonin syndrome: agitation, hallucinations, loss of coordination, rapid heartbeat, elevated body temperature, rapid changes in blood pressure, hyperreflexia, diarrhea, drowsiness, nausea, vomiting. The most severe form of serotonin syndrome may resemble neuroleptic malignant syndrome. Symptoms of neuroleptic malignant syndrome may include fever, rapid heartbeat, sweating, muscle rigidity, confusion, and increased levels of muscle enzymes (detected in blood tests).

If any of the following adverse reactions occur, contact a doctor:

cough, wheezing, shortness of breath and high fever;
black (tarry) stools or blood in the stool;
yellowing of the skin or whites of the eyes, itching, or dark urine, which may be symptoms of hepatitis;
heart problems such as rapid or irregular heartbeat, elevated blood pressure;
visual disturbances such as blurred vision, dilated pupils;
nervous system disorders such as dizziness, tingling sensation, movement coordination problems, seizures or convulsions;
psychiatric disturbances such as excessive restlessness and euphoria (feeling of unnatural excitement);
withdrawal symptoms (see sections "How to take Prefaxine" and "Stopping Prefaxine");
prolonged bleeding time – in case of cuts, the time required to stop bleeding may be slightly longer than usual.

Complete list of adverse reactions

Very common (occur in more than 1 in 10 patients)

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

Common (occur in 1 to 10 in 100 patients)

decreased appetite;
confusion; feeling detached (or separated) from oneself; anorgasmia; reduced sexual desire; nervousness; insomnia; unusual dreams;
drowsiness; tremor; tingling; increased muscle tension;
visual disturbances, including blurred vision; dilated pupils; inability of the eye to accommodate (automatic adjustment of focus from distant to near objects);
ringing in the ears (tinnitus);
palpitations;
increased blood pressure; sudden flushing;
yawning;
vomiting; constipation; diarrhea;
increased frequency of urination; difficulty passing urine;
menstrual disorders such as heavy bleeding or more frequent irregular bleeding; ejaculation/orgasm disorders (in men); erectile dysfunction (impotence);
weakness (asthenia); fatigue;
increased blood cholesterol levels.

Uncommon (occur in 1 to 10 in 1,000 patients)

hallucinations; feeling detached from reality; agitation; orgasm disorders (in women); apathy; feeling of excessive excitement; teeth grinding;
feeling anxious or inability to sit or stand still; fainting; involuntary muscle movements; coordination and balance disturbances; taste disturbances;
rapid heartbeat; dizziness (especially when standing up too quickly);
shortness of breath;
vomiting blood; black, tarry stools (faeces) or blood in the stool, which may indicate internal bleeding;
generalized skin swelling, especially of the face, lips, tongue, throat, hands or feet and/or presence of raised, itchy rash; light sensitivity; bruising; rash; excessive hair loss;
urinary retention;
weight gain; weight loss.

Rare (occur in 1 to 10 in 10,000 patients)

convulsions;
urinary incontinence;
excessive excitement, racing thoughts and reduced need for sleep (mania).

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

reduced platelet count, leading to increased risk of bruising or bleeding; blood disorders which may increase the risk of infection;
severe vaginal bleeding occurring shortly after childbirth (postpartum hemorrhage), see additional information in subsection "Pregnancy and breastfeeding" in section 2;
swelling of the face or tongue, difficulty breathing or shortness of breath, often with skin rash (may indicate a severe allergic reaction);
excessive water retention in the body (SIADH);
decreased sodium levels in the blood;
suicidal thoughts and behavior; cases of suicidal thoughts and behavior have been reported during treatment with venlafaxine or shortly after discontinuation (see section 2 "Important information before taking Prefaxine");
confusion with frequent hallucinations (delirium); aggressive behavior;
high fever with muscle stiffness, confusion or agitation, sweating, or uncontrolled muscle movements may be symptoms of a serious condition called neuroleptic malignant syndrome; feelings of euphoria, drowsiness, persistent rapid eye movements, clumsiness, restlessness, feeling drunk, sweating or muscle stiffness, which are symptoms of serotonin syndrome; muscle stiffness, cramps and uncontrolled muscle movements;
severe eye pain and visual disturbances or blurred vision;
dizziness;
low blood pressure; abnormal, rapid or irregular heartbeat which may lead to fainting; unexpected bleeding, e.g. bleeding gums, blood in urine or vomit, unexpected appearance of bruises or broken blood vessels (ruptured veins);
cough, wheezing, shortness of breath and high fever, which are symptoms of lung inflammation associated with increased white blood cell count (pulmonary eosinophilia);
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, flu-like symptoms, which are symptoms of hepatitis; minor changes in liver enzyme activity in blood;
skin rash which may lead to blistering and peeling of the skin; itching; mild rash;
unexplained muscle pain, tenderness or weakness (rhabdomyolysis);
abnormal milk secretion in women.

Prefaxine may sometimes cause adverse reactions that the patient is unaware of, such as increased blood pressure or abnormal heart function, minor changes in liver enzyme levels, sodium or cholesterol levels in the blood. In even rarer cases, Prefaxine may impair platelet function, leading to an increased risk of petechiae or bleeding. Therefore, the doctor may periodically recommend blood tests, especially during long-term treatment with Prefaxine.

Reporting of adverse reactions

If any adverse reactions occur, including any not listed in this leaflet, inform your doctor, pharmacist, or nurse. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C
02-222 Warsaw
Tel.: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorization holder.

Reporting adverse reactions helps to gather more information on the safety of this medicine.

5. How to store Prefaxine

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 stated month.
The marking on the packaging following "EXP" indicates the expiry date, and following "Lot" or "LOT" indicates the batch number.
Do not store above 30°C.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This 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).
Other ingredients are:
37.5 mg prolonged-release, hard capsules:
Capsule contents: hypromellose, ammonio methacrylate copolymer (type B), sodium lauryl sulfate, magnesium stearate;
Coating composition: basic butyl methacrylate copolymer 12.5%;
Capsule shell composition: gelatin, titanium dioxide (E171);
Printing 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;
Coating composition: basic butyl methacrylate copolymer 12.5%;
Capsule shell composition: gelatin, titanium dioxide (E171), iron oxide red (E172);
Printing 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;
Coating composition: basic butyl methacrylate copolymer 12.5%;
Capsule shell composition: gelatin, titanium dioxide (E171), erythrosine (E127), indigo carmine (E132);
Printing ink: shellac, iron oxide black (E172), propylene glycol (E1520).

What Prefaxine looks like and contents of the pack

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

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

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

Packs contain 28 prolonged-release, hard capsules.

Marketing Authorisation Holder and Manufacturer
Zakłady Farmaceutyczne POLPHARMA S.A.
ul. Pelplińska 19, 83-200 Starogard Gdański
tel. +48 22 364 61 01