Axyven

Package leaflet: Information for the user

Axyven, 37.5 mg, prolonged-release tablets
Axyven, 75 mg, prolonged-release tablets
Axyven, 150 mg, prolonged-release tablets
Venlafaxine
Please read all of this leaflet carefully before taking this medicine, because it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm someone else, even if their symptoms are the same.
• If you experience any adverse reactions, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of the leaflet

1. What Axyven is and what it is used for
2. Important information before taking Axyven
3. How to take Axyven
4. Possible side effects
5. How to store Axyven
6. Contents of the pack and other information

1. What Axyven is and what it is used for

Axyven contains the active substance venlafaxine.
Axyven is an antidepressant medicine that belongs to a group of medicines called serotonin and noradrenaline reuptake inhibitors (SNRIs). This group of medicines is used in the treatment of depression and other conditions such as anxiety disorders. The exact mechanism of action of antidepressant medicines is not fully understood, but they may help by increasing the levels of serotonin and noradrenaline in the brain.
Axyven is used to treat adult patients with depression. Axyven is also indicated for the treatment of the following anxiety disorders in adult patients: generalized anxiety disorder, social phobia (fear or avoidance of social situations), and panic disorder (panic attacks).
It is important that treatment of depression and anxiety disorders is properly managed to improve the patient's well-being. If left untreated, your condition may not improve, may worsen, and may become more difficult to treat.

2. Important information before taking Axyven

When not to take Axyven:

• 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 certain medicines belonging to the group of irreversible monoamine oxidase inhibitors (MAOIs), used in the treatment of depression or Parkinson's disease. Taking irreversible MAOIs together with Axyven may cause severe or even life-threatening adverse reactions.
  Also, at least 7 days should elapse after stopping Axyven before starting any medicine from the MAOI group (see also section "Axyven and other medicines" and information under "Serotonin syndrome").

Warnings and precautions
Before starting treatment with Axyven, discuss the following with your doctor or pharmacist:

• If the patient is taking other medicines that, when used together with Axyven, may increase the risk of serotonin syndrome (see section "Axyven and other medicines").
• If the patient has problems with swallowing or gastrointestinal disorders that impair the ability to swallow or properly evacuate food.
• If the patient has eye diseases, such as certain types of glaucoma (increased pressure in the eyeball).
• If the patient has a history of high blood pressure.
• If the patient has previously had heart diseases.
• If the patient has previously experienced cardiac arrhythmias.
• If the patient has previously had seizures (epilepsy).
• If the patient has previously experienced low sodium levels in the blood (hyponatremia).
• If the patient has previously had bleeding disorders (tendency to bruise or bleed) or is taking other medicines that may increase the risk of bleeding, e.g. warfarin (used to prevent blood clots), or if the patient is pregnant (see "Pregnancy, breastfeeding and fertility").
• If the patient or any of their family members have previously had mania or bipolar disorder (feelings of excessive excitement or euphoria).
• If the patient has previously exhibited aggressive behavior.

During the first few weeks of treatment, Axyven may cause feelings of restlessness or inability to sit still or remain in one place. If such symptoms occur, inform the treating doctor.
Do not consume alcohol during treatment with Axyven, as it 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 have thoughts of self-harm or suicide. These symptoms or behaviors may worsen at the beginning of treatment with antidepressant medicines, as these medicines usually take effect after about two weeks or sometimes later. Such thoughts may also occur when the dose is reduced or during discontinuation of Axyven treatment.
These thoughts may be more likely in patients who:

• Have previously experienced suicidal thoughts or self-harming behavior.
• Are young adults. Clinical trial data indicate an increased risk of suicidal behavior in young adults (under 25 years of age) with psychiatric disorders treated with antidepressant medicines.

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 relatives or friends about the depression or anxiety disorder and ask them to read this leaflet. The patient may seek help from relatives or friends and ask them to inform the patient if they notice worsening of depression or anxiety, or concerning changes in behavior.

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

Patients with diabetes
Blood glucose levels may change during treatment with Axyven. Therefore, the dosage of antidiabetic medicines may require adjustment.

Sexual dysfunction
Medicines such as Axyven (so-called SSRIs or SNRIs) may cause symptoms of sexual dysfunction (see section 4). In some cases, these symptoms persisted after discontinuation of treatment.

Children and adolescents
Axyven should generally not be used in children and adolescents under 18 years of age. It should also be known that when this class of medicines is used, patients under 18 years of age are at increased risk of adverse reactions such as suicide attempts, suicidal thoughts, and hostility (particularly aggression, defiant behaviors, and anger).
Nevertheless, a doctor may prescribe this medicine to patients under 18 years of age if they consider it to be in their best interest. If a doctor has prescribed this medicine to a patient under 18 years of age and there are any concerns, consult the treating doctor.
Inform the doctor if any of the symptoms listed below occur or worsen in patients under 18 years of age taking Axyven. Furthermore, long-term safety data on the use of this medicine in this age group regarding effects on growth, maturation, and cognitive and behavioral development are currently lacking.

Axyven and 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 Axyven can be used together with other medicines.
Do not start or stop taking other medicines, including over-the-counter medicines, natural or herbal remedies, without first consulting a doctor or pharmacist.

• Do not take monoamine oxidase inhibitors (MAOIs) together with Axyven. These are used in the treatment of depression or Parkinson's disease. Inform the doctor if the patient has taken these medicines within the last 14 days (MAOIs; see section "Important information before taking Axyven").
• Serotonin syndrome: A potentially life-threatening condition or reactions resembling neuroleptic malignant syndrome (see section "Possible side effects") may occur during treatment with venlafaxine, especially when used concomitantly with other medicines.

Examples of such medicines include:

• Triptans (used for migraine headaches).
• Other medicines used to treat depression, such as: selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants, or medicines containing lithium.
• Medicines containing amphetamine derivatives (used to treat attention deficit hyperactivity disorder (ADHD), narcolepsy, and obesity).
• Medicines containing the antibiotic linezolid (used to treat infections).
• Medicines containing moclobemide, MAOIs (used to treat depression).
• Medicines containing sibutramine (used for weight loss).
• Medicines containing opioids (e.g. buprenorphine, tramadol, fentanyl, tapentadol, pethidine, or pentazocine) used to treat severe pain.
• Medicines containing dextromethorphan (used to treat cough).
• Medicines containing methadone (used to treat opioid dependence or severe pain).
• Medicines containing methylene blue (used to treat high levels of methemoglobin in the blood).
• Medicines containing St. John's wort (also known as Hypericum perforatum, natural or herbal remedies used to treat mild depression).
• Medicines containing tryptophan (used for sleep problems and depression).
• Antipsychotic medicines (used to treat symptoms such as hearing, seeing, or feeling things that are not real, false beliefs, unusual suspiciousness, unclear thinking, and withdrawal behavior).

Subjective and objective symptoms of serotonin syndrome may include a combination of the following:
agitation, hallucinations, loss of coordination, rapid heartbeat, elevated body temperature, rapid changes in blood pressure, hyperreflexia, diarrhea, coma, nausea, vomiting.
In its most severe form, serotonin syndrome may resemble neuroleptic malignant syndrome.
Objective and subjective symptoms may include: a combination of fever, rapid heartbeat, sweating, severe muscle rigidity, confusion, and increased levels of muscle enzymes (detected in blood tests).
If serotonin syndrome is suspected, seek immediate medical attention 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:

• Antiarrhythmic medicines such as: quinidine, amiodarone, sotalol, or dofetilide (used to treat cardiac arrhythmias).
• 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 Axyven and should therefore be used with caution. It is especially important to inform the doctor or pharmacist 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 high blood pressure and heart diseases).

Axyven with food, drink and alcohol
Axyven should be taken with food (see section 3. "How to take Axyven").
Do not consume alcohol during treatment with Axyven. 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, breastfeeding and fertility
If the patient is pregnant, breastfeeding, suspects she may be pregnant, or is planning to become pregnant, she should consult her doctor before taking this medicine.
The patient should take Axyven only after discussing with the doctor the potential benefits and potential risks to the unborn child.
Ensure that the doctor and (or) midwife are aware that the patient is taking Axyven.
Taking similar medicines (SSRIs) during pregnancy may increase the risk of serious complications in the newborn, known as persistent pulmonary hypertension of the newborn (PPHN), which manifests as rapid breathing and cyanosis. These symptoms usually appear within the first 24 hours after birth. If such symptoms occur in the newborn, contact a doctor and (or) midwife immediately.
Taking Axyven late in 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 Axyven, she should inform her doctor or midwife so they can provide appropriate advice.
If the patient takes this medicine during pregnancy, her newborn may experience, in addition to breathing difficulties, other symptoms such as problems with sucking. If the patient is concerned about such symptoms in the newborn after birth, contact the doctor and (or) midwife, who will be able to provide appropriate advice.
Axyven passes into breast milk. There is a risk of the medicine affecting the infant. Therefore, discuss this issue with the doctor, who will decide whether to discontinue breastfeeding or stop treatment with this medicine.

Driving and using machines
Do not drive, use any tools, or operate any machinery until the patient knows how Axyven affects them.

Axyven contains lactose
If the patient has been informed by a doctor that they have an intolerance to certain sugars, they should contact the doctor before starting to take this medicine.

3. How to take Axyven

This medicine should always be taken exactly as prescribed by your doctor. If in doubt, consult your doctor or pharmacist.
The usual recommended starting dose for the treatment of depression, generalized anxiety disorders, and social phobia is 75 mg per day. This dose may be gradually increased by the doctor, if necessary, up to a maximum dose of 375 mg per day in the case of depression.
For panic attacks, treatment should be initiated with a lower dose (37.5 mg), which should then be gradually increased. The maximum dose for the treatment of generalized anxiety disorders, social phobia, and panic disorder is 225 mg per day.
Axyven should be taken daily at approximately the same time, regardless of whether it is taken in the morning or in the evening.
Tablets must be swallowed whole with liquid and must not be divided, crushed, chewed, or dissolved.
Axyven should be taken with food.
If the patient has liver or kidney problems, this should be reported to the doctor, as a dose adjustment of Axyven may be necessary.
Do not discontinue treatment with Axyven without consulting your doctor (see section "Discontinuing Axyven").

Taking more Axyven than prescribed
If a patient has taken more than the prescribed dose of Axyven, they should contact their doctor or pharmacist immediately.
Overdose may be life-threatening, especially when taken with alcohol and/or certain medicines (see "Axyven with other medicines").
Symptoms of possible overdose may include rapid heartbeat, disturbances in consciousness (from drowsiness to coma), visual disturbances, seizures or convulsions, and vomiting.

Missing a dose of Axyven
If a patient forgets to take a dose, they should take it as soon as possible. However, if it is almost time for the next dose, the missed dose should be skipped and only the regular dose should be taken at the usual time. Do not take a double dose to make up for a missed dose. Do not take more medicine in one day than the daily dose of Axyven prescribed by the doctor.

Discontinuing Axyven
Do not stop treatment or reduce the dose of Axyven without consulting your doctor, even if you feel better. If your doctor decides that Axyven can be discontinued, they will inform you how to gradually reduce the dose before stopping treatment completely. In patients discontinuing Axyven, especially after abrupt cessation or too rapid dose reduction, adverse effects may occur. Some patients may experience symptoms such as suicidal thoughts, aggression, feeling tired, dizziness, a sensation of emptiness in the head, headache, insomnia, nightmares, dry mouth, loss of appetite, nausea, diarrhea, nervousness, agitation, confusion, ringing in the ears, tingling sensations, or rarely, an electric shock-like sensation, weakness, sweating, convulsions, flu-like symptoms, visual disturbances, and increased blood pressure (which may cause headaches, dizziness, ringing in the ears, sweating, etc.).
Your doctor will advise you on how to gradually discontinue Axyven. This process may take several weeks or months. In some patients, a very gradual discontinuation over months or longer may be necessary. If any of the listed symptoms 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 all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
If any of the following adverse reactions occur, stop taking
the medicine Axyven immediately. Contact a doctor immediately or go to the emergency department
of the nearest hospital.
Uncommon (may occur in fewer than 1 in 100 people)

• Swelling of the face, lips, tongue, throat, hands or feet and (or) raised, itchy rash (urticaria), difficulty swallowing or breathing.

Rare (may occur in fewer than 1 in 1,000 people)

• Chest tightness, wheezing, difficulty swallowing or breathing.
• Severe rash, itching or urticaria (red or pale raised rash, often accompanied by itching).
• Subjective and objective symptoms of serotonin syndrome may include: psychomotor agitation, hallucinations, loss of motor coordination, increased heart rate, elevated body temperature, rapid changes in blood pressure, hyperreflexia, diarrhea, somnolence, nausea, vomiting. In its most severe form, serotonin syndrome may resemble neuroleptic malignant syndrome. Subjective and objective symptoms of neuroleptic malignant syndrome may include a combination of fever, increased heart rate, sweating, severe muscle rigidity, disorientation, and increased muscle enzyme levels (detected in blood tests).
• Signs of infection such as: high fever, chills, tremors, headache, sweating, flu-like symptoms. This may result from a blood disorder leading to increased risk of infection.
• Severe rash which may lead to formation of serious blisters and skin peeling.
• Muscle pain of unknown origin, tenderness or weakness. These may be symptoms of rhabdomyolysis.

Frequency not known (cannot be estimated from available data)

• Symptoms of a condition known as stress cardiomyopathy, including: chest pain, shortness of breath, dizziness, fainting, irregular heartbeat.

Other adverse reactions which should be reported to a doctor (frequency of these adverse reactions is listed below under "Other adverse reactions") include:

• Cough, wheezing and shortness of breath, possibly accompanied by high fever.
• Black (tarry) stools or blood in the stool.
• Itching, yellowing of the skin or eyes, dark urine, which may be signs of liver inflammation.
• Heart disorders such as: rapid or irregular heartbeat, increased blood pressure.
• Eye disorders such as: blurred vision, dilated pupils.
• Nervous system disorders such as: dizziness, tingling sensation, movement coordination disorders (muscle spasms or stiffness), seizures or convulsions.
• Psychiatric disorders such as: excessive restlessness and feeling of unnatural excitement.
• Withdrawal symptoms (see sections "How to take Axyven", "Stopping treatment with Axyven").
• Prolonged bleeding – if the patient is injured or cut, bleeding may take longer than usual to stop.

There is no need to worry if the patient notices a tablet in the stool while taking Axyven.
Venlafaxine is slowly released from the tablet as it passes through the entire length of the
gastrointestinal tract. The tablet shell does not dissolve and is excreted in the stool. Therefore,
even if the patient sees a tablet in the stool, there is no cause for concern – the dose of venlafaxine has been absorbed.
Other adverse reactions
Very common (may occur in more than 1 in 10 patients)

• Dizziness, headache, drowsiness.
• Insomnia.
• Nausea, dry mouth, constipation.
• Sweating (including night sweats).

Common (may occur in fewer than 1 in 10 patients)

• Decreased appetite.
• Disorientation, feeling of detachment (or separation) from oneself, anorgasmia, decreased libido, agitation, nervousness, unusual dreams.
• Tremor, feeling of restlessness or inability to sit or stand still, tingling, taste disturbances, increased muscle tension.
• Vision disorders, including: blurred vision, dilated pupils, inability of the eye to automatically adjust focus from distant to near objects.
• Ringing in the ears (tinnitus).
• Rapid heartbeat, palpitations.
• Increased blood pressure, flushing.
• Shortness of breath, yawning.
• Vomiting, diarrhea.
• Mild rash, itching.
• Increased frequency of urination, urinary retention, difficulty urinating.
• Menstrual irregularities such as: heavier bleeding or increased frequency of irregular bleeding, ejaculation/orgasm disorders (in men), erectile dysfunction (impotence).
• Weakness (asthenia), fatigue, chills.
• Weight gain, weight loss.
• Increased cholesterol levels.

Uncommon (may occur in fewer than 1 in 100 patients)

• Excessive excitement, racing thoughts and reduced need for sleep (mania).
• Hallucinations, feeling of detachment (or separation) from reality, orgasm disorders, lack of feelings or emotions, feeling of excessive excitement, teeth grinding.
• Fainting, uncontrolled muscle movements, coordination and balance disorders.
• Dizziness (especially when standing up too quickly), decreased blood pressure.
• Blood in vomit, black tarry stools or blood in stool, which may indicate internal bleeding.
• Light sensitivity, bruising, excessive hair loss.
• Inability to control urination.
• Stiffness, spasms and uncontrolled muscle movements.
• Minor changes in liver enzyme activity in blood.

Rare (may occur in fewer than 1 in 1,000 patients)

• Convulsions or seizures.
• Cough, wheezing and shortness of breath, possibly accompanied by high fever.
• Disorientation and confusion, often accompanied by hallucinations (delirium).
• Excessive water retention in the body (known as syndrome of inappropriate antidiuretic hormone secretion, SIADH).
• Decreased sodium levels in blood.
• Severe eye pain, worsening or blurred vision.
• Irregular, rapid or irregular heartbeat, which may lead to fainting.
• Severe abdominal or back pain (which may indicate serious problems with the intestines, liver or pancreas).
• Itching, yellowing of the skin or whites of the eyes, dark urine or flu-like symptoms, which are signs of liver inflammation.

Very rare (may occur in fewer than 1 in 10,000 people)

• Prolonged bleeding, which may be a sign of reduced platelet count, leading to increased risk of bruising or bleeding.
• Unusual milk production in women.
• Unexpected bleeding, e.g. bleeding from gums, blood in urine or vomit, appearance of unexpected bruises or broken blood vessels (ruptured veins).

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

• Suicidal thoughts and behaviors; suicidal thoughts and behaviors have been reported during treatment with venlafaxine or shortly after discontinuation of treatment (see section 2. "Important information before using Axyven").
• Aggressive behavior.
• Dizziness.
• Severe vaginal bleeding occurring shortly after childbirth (postpartum hemorrhage), see additional information in subsection "Pregnancy, breastfeeding and effect on fertility" in section 2.

Axyven may sometimes cause adverse reactions of which the patient may be unaware, such as: increased blood pressure, abnormal heart function, minor changes in liver enzyme activity, sodium or cholesterol levels in blood. Even more rarely, Axyven may cause platelet function disorders, increasing the risk of petechiae or bleeding. Therefore, the doctor may recommend periodic blood tests, especially during long-term treatment with Axyven.
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 of the Office for Medicinal Products, Medical Devices and Biocidal Products:
Al. Jerozolimskie 181C, 02-222 Warsaw, tel.: 22 49-21-301, fax: 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 collect more information on the safety of the medicine.

5. How to store Axyven

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging after EXP.
The expiry date refers to the last day of the stated month.
No special storage instructions apply.
Blister packs: store in the original packaging to protect from moisture.
HDPE bottle: keep the bottle tightly closed to protect from moisture.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. This will help protect the environment.

6. Contents of the pack and other information

What Axyven contains

• The active substance in this medicine is venlafaxine.

Each prolonged-release tablet contains 37.5 mg, 75 mg, or 150 mg of venlafaxine
(as hydrochloride).
The other ingredients are:
Core: mannitol (E 421), povidone K 90, polyethylene glycol 400, microcrystalline cellulose (E 460(i)),
anhydrous colloidal silica, magnesium stearate (E 470b).
Coating: cellulose acetate (320S NF), cellulose acetate (398-10NF), polyethylene glycol 400,
Opadry White Y-30-18037 (hypromellose, lactose monohydrate, titanium dioxide (E 171), triacetin).

What Axyven looks like and contents of the pack
37.5 mg: round, 7 mm in diameter, biconvex, white to off-white prolonged-release tablets, with a (small) notch on one side.
75 mg: round, 7.5 mm in diameter, biconvex, white to off-white prolonged-release tablets, with a (small) notch on one side.
150 mg: round, 9.5 mm in diameter, biconvex, white to off-white prolonged-release tablets, with a (small) notch on one side.

Axyven is available in blister packs containing 28 and 30 prolonged-release tablets, and in plastic bottles containing 100 prolonged-release tablets.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Exeltis Poland Sp. z o.o.
Szamocka Street 8
01-748 Warsaw
Poland

Manufacturer
Laboratorios LICONSA, S.A.
Avda. Miralcampo no 7
Poligono Industrial Miralcampo
19200 Azuqueca de Henares
Spain

This medicinal product is authorised in the European Economic Area and the United Kingdom (Northern Ireland) under the following names:
Sweden Venlafaxin 1A Farma 37.5/75/150/225 mg prolonged-release tablets
Estonia Venlafaxine Wörwag Pharma 37.5/75/150/225 mg, active substance prolonged-release tablets
Greece SEROSMINE 37.5/75/150/225 mg prolonged-release tablet
France VENLAFAXINE BIPHAR 150/225 mg prolonged-release tablet
Italy Zarelis 37.5/75/150/225 mg prolonged-release tablet
Netherlands Venlafaxine Aurobindo 225 mg prolonged-release tablet
Poland Axyven 37.5/75/150 mg prolonged-release tablets
Portugal Zarelix 37.5/75/150/225 mg prolonged-release tablets
United Kingdom Venlafaxine XL 37.5/75/150/225 mg prolonged-release tablets