Package Leaflet: Information for the User

Ixilania 75 mg prolonged-release hard capsules, 150 mg prolonged-release hard capsules

Venlafaxine
Generic medicinal product
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 questions, ask your doctor or pharmacist.
This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it may be harmful to them.
If you experience any side effects, including those not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Contents of this leaflet:

What Ixilania is and what it is used for
What you need to know before taking Ixilania
How to take Ixilania
Possible side effects
How to store Ixilania
Contents of the pack and other information

1. What Ixilania is and what it is used for

Ixilania contains the active substance venlafaxine.
Ixilania is an antidepressant belonging to a group of medicines called serotonin and noradrenaline reuptake inhibitors (SNRIs). This group of medicines is used to treat depression and other conditions, such as anxiety disorders. It is thought that people who are depressed and/or anxious have lower levels of serotonin and noradrenaline in the brain. The exact way antidepressants work is not fully understood; however, they may help by increasing the levels of serotonin and noradrenaline in the brain.
Ixilania is a treatment for adults with depression. It is also a treatment for adults with the following anxiety disorders: generalized anxiety disorder, social anxiety disorder (fear of or tendency to avoid social situations), and panic disorder (panic attacks). Appropriate treatment of depression or anxiety disorders is important to help you feel better. If left untreated, your condition may not improve and may become more severe and more difficult to treat.

2. What you need to know before taking Ixilania

Do not take Ixilania

if you are allergic to venlafaxine or to 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), used to treat depression or Parkinson’s disease. Taking an irreversible MAOI together with Ixilania may cause serious or even life-threatening side effects. In addition, you must wait at least 7 days after stopping treatment with Ixilania before taking any MAOI (see also the section “Other medicines and Ixilania” and the information under the same section regarding “Serotonin syndrome”).

Warnings and precautions
Talk to your doctor or pharmacist before taking Ixilania:

If you are using other medicines which, when taken together with Ixilania, may increase the risk of developing serotonin syndrome (see section “Other medicines and Ixilania”).
If you have eye problems, such as certain types of glaucoma (increased pressure inside the eye).
If you have a history of high blood pressure.
If you have a history of heart problems.
If you have been told you have an abnormal heart rhythm.
If you have a history of seizures.
If you have a history of low sodium levels in your blood (hyponatraemia).
If you have a tendency to bruise easily or a tendency to bleed easily (history of bleeding disorders), 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 Pregnancy and breastfeeding).
If you have a history, or if someone in your family has had, mania or bipolar disorder (feelings of over-excitement or euphoria).
If you have a history of aggressive behaviour.

During the first few weeks of treatment, Ixilania may cause a feeling of restlessness or an inability to sit still. If you experience these symptoms, you must inform your doctor.
Suicidal thoughts and worsening of your depression or anxiety disorder
If you are depressed and/or suffer from anxiety disorders, you may sometimes develop thoughts of harming yourself or of suicide. These thoughts may increase when you first start taking antidepressants, because it takes time for such medicines to take effect, usually about two weeks but sometimes longer.
You are more likely to have these thoughts:

If you have previously had thoughts of suicide or of harming yourself.
If you are young. Clinical studies have shown an increased risk of suicidal behaviour in young people (under 25 years) with psychiatric disorders who were treated with an antidepressant.

If you have thoughts of harming yourself or of suicide at any time, contact your doctor or go immediately to the hospital.
It may help to tell a close relative or friend that you are depressed or suffer from an anxiety disorder, and ask them to read this leaflet. You may ask them to inform you if they think your depression or anxiety is worsening, or if they are concerned about changes in your behaviour.
Dry mouth
Dry mouth occurs in 10% of patients treated with venlafaxine. This may increase the risk of dental caries. You should therefore pay particular attention to your oral hygiene.
Diabetes
Blood glucose levels may be altered by Ixilania. Therefore, it may be necessary to adjust the dose of your diabetes treatment.
Sexual problems
Medicines such as Ixilania (so-called serotonin-noradrenaline reuptake inhibitors, SNRIs) can cause symptoms of sexual dysfunction (see section 4). In some cases, these symptoms have persisted after discontinuation of treatment.
Children and adolescents
Ixilania is normally not to be used in children and adolescents under 18 years of age. In addition, you should know that patients under 18 years of age have a higher risk of adverse effects, such as suicide attempts, suicidal thoughts and hostility (mainly aggression, oppositional behaviour and anger), when taking this class of medicines. Nevertheless, your doctor may prescribe this medicine for patients under 18 years of age if they consider it to be in their best interest. If your doctor has prescribed this medicine for a patient under 18 years of age and you wish to discuss this, talk to your doctor. You must inform your doctor if any of the listed symptoms appear or worsen when a patient under 18 years of age is taking Ixilania. In addition, the long-term effects of this medicine on growth, maturation and cognitive and behavioural development in this age group have not been established.
Other medicines and Ixilania
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.
Your doctor will decide whether you can use Ixilania with other medicines.
Do not start or stop treatment with other medicines, including over-the-counter medicines and herbal preparations, before consulting your doctor or pharmacist.

Monoamine oxidase inhibitors used to treat depression or Parkinson’s disease must not be taken with Ixilania. Inform your doctor if you have taken these medicines within the last 14 days (MAOIs: see section “What you need to know before taking Ixilania”).
Serotonin syndrome :

A potentially life-threatening condition or reactions similar to Neuroleptic Malignant Syndrome (NMS) (see section “Possible side effects”) may occur with venlafaxine treatment, especially when taken with other medicines.
Examples of such medicines include:
o Triptans (used for migraine)
o Other medicines for the treatment of depression, for example SNRIs, SSRIs, tricyclics, or medicines containing lithium
o Medicines containing amphetamines (used to treat attention deficit hyperactivity disorder (ADHD), narcolepsy and obesity)
o Medicines containing linezolid, an antibiotic (used to treat infections)
o Medicines containing moclobemide, an MAOI (used to treat depression)
o Medicines containing sibutramine (used for weight loss)
o Medicines containing tramadol, fentanyl, tapentadol, pethidine, or pentazocine (used to treat severe pain)
o Medicines containing dextromethorphan (used to treat cough)
o Medicines containing methadone (used to treat opioid dependence or severe pain)
o Medicines containing methylene blue (used to treat high levels of methaemoglobin in the blood)
o Herbal preparations containing St. John’s wort (also known as Hypericum perforatum, a herbal remedy used to treat mild depression)
o Products containing tryptophan (used for sleep disorders and depression)
o Antipsychotics (used to treat a condition with symptoms such as hearing, seeing or perceiving things that are not real, false beliefs, strange suspicions, confused thinking and withdrawal)
Signs and symptoms of serotonin syndrome may include a combination of: restlessness, hallucinations, loss of coordination, rapid heartbeat, increased body temperature, rapid fluctuations in blood pressure, overactive reflexes, diarrhoea, 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).
If you think you have serotonin syndrome, contact your doctor immediately or go to the nearest hospital emergency department.
You must inform your doctor if you are taking medicines that may affect heart rhythm.
Examples of such medicines include:

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

The following medicines may also interfere with Ixilania and should be used with caution. It is particularly important that you inform your doctor or pharmacist if you are taking medicines containing:

Ketoconazole (an antifungal medicine)
Haloperidol or risperidone (for the treatment of psychiatric disorders)
Metoprolol (a beta-blocker for the treatment of high blood pressure and heart problems)

Ixilania with food, drinks and alcohol
You should take Ixilania with food (see section “How to take Ixilania”).
You must not drink alcohol while taking Ixilania.
Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant or are planning to become pregnant, or if you are breastfeeding, consult your doctor or pharmacist before taking this medicine. You should use Ixilania only after discussing with your doctor the potential benefits and possible risks to the fetus.
Ensure that your midwife and/or doctor know that you are taking Ixilania. When taken during pregnancy, similar medicines (called SSRIs) may increase the risk of a serious condition in newborns called persistent pulmonary hypertension of the newborn (PPHN). This condition causes the newborn to breathe rapidly and appear bluish. These symptoms usually begin within the first 24 hours of the baby’s life. If this occurs, contact your midwife and/or doctor immediately.
If you take IXILANIA near the end of your pregnancy, there may be an increased risk of heavy vaginal bleeding shortly after delivery, especially if you have bleeding disorders (tendency to bleed easily). Inform your doctor or midwife that you are taking IXILANIA so they can advise you on what to do.
If you are using this medicine during pregnancy, in addition to breathing difficulties, another symptom your baby may have at birth is difficulty feeding adequately. If you are concerned that your baby may show these symptoms at birth, contact your doctor and/or midwife, who will assist you.
Ixilania is excreted in breast milk. There is a risk of effects on the infant. Therefore, you should discuss this with your doctor, who will decide whether you should discontinue breastfeeding or the treatment with this medicine.
Driving and using machines
Do not drive and do not use tools or machines until you know how this medicine affects you.

3. How to take Ixilania

Take this medicine exactly as stated in this leaflet or as directed by your doctor. If you have any doubts, consult your doctor or pharmacist.
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, up to a maximum dose 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 subsequently increase the dose gradually. The maximum dose for generalized anxiety disorder, social anxiety disorder, and panic disorder is 225 mg per day.
Take Ixilania at approximately the same time each day, in the morning or evening. The capsules must be swallowed whole with liquid and must not be opened, broken, chewed, or dissolved.
Ixilania must be taken with food.
If you have liver or kidney problems, discuss this with your doctor, as a dose adjustment of this medicine may be necessary.
Do not stop treatment with this medicine without consulting your doctor (see section “If you stop taking Ixilania”).

If you take more Ixilania than you should
Contact your doctor or pharmacist immediately if you take more medicine than prescribed.
Symptoms of a possible overdose may include rapid heartbeat, changes in consciousness (ranging from drowsiness to coma), blurred vision, seizures, and vomiting.

If you forget to take Ixilania
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 as usual. Do not take a double dose to make up for the forgotten dose. Do not take more than the prescribed daily dose of Ixilania in a single day.

If you stop taking Ixilania
Do not stop treatment or reduce the dose without consulting your doctor, even if you feel better. If your doctor decides that you no longer need Ixilania, they may instruct you to gradually reduce the dose before stopping treatment completely. It is known that adverse effects may occur when patients discontinue treatment with this medicine, especially if it is stopped abruptly or if the dose is reduced too quickly. Some patients may experience symptoms such as fatigue, dizziness, lightheadedness, headache, insomnia, nightmares, dry mouth, loss of appetite, nausea, diarrhea, nervousness, agitation, confusion, tinnitus, 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 Ixilania. If you experience any of these or other bothersome symptoms, consult your doctor for further advice.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone experiences them.
If you experience any of the side effects listed below, do not take any more Ixilania.
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 noticeable skin rash with itching (urticaria), difficulty swallowing or breathing

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

Chest tightness, wheezing, difficulty swallowing or breathing
Severe skin rash, itching, or hives (raised patches of red or pale skin that often itch)
Signs and symptoms of serotonin syndrome may include agitation, 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 (detected by blood tests).

Signs of infection such as high temperature, chills, shivering, headache, sweating, flu-like symptoms. This may be due to a blood disorder causing an increased risk of infection.
Severe skin rash that may cause extensive blistering and skin peeling
Unexplained muscle pain, tenderness, or weakness. This may be a sign of rhabdomyolysis.

Other side effects that you must report to your doctor are (the frequencies of these side effects are included in the list “Other side effects”):

Cough, wheezing, and shortness of breath, which may be accompanied by high temperature
Black stools (tarry appearance) or blood in the stools
Itching, yellowing of the eyes or skin, or dark urine, which may be symptoms of liver inflammation (hepatitis)
Heart problems, such as rapid or irregular heartbeat, increased blood pressure
Eye problems, such as blurred vision, dilated pupils
Nervous system problems, such as dizziness, tingling, movement disorders (muscle spasms or stiffness), seizures
Psychiatric problems, such as hyperactivity and feeling excessively excited
Withdrawal syndrome (see section “How to take Ixilania, If you stop taking Ixilania”)
Prolonged bleeding – if you get cuts or injuries, it may take longer than usual to stop bleeding

Do not be alarmed if you notice small granules or white spheres in your stools after taking this medicine.
Ixilania capsules contain spheroids (small white spheres) that contain the active substance venlafaxine. These spheroids are released from the capsule in the stomach. As the spheroids travel through the entire length of your gastrointestinal tract, venlafaxine is slowly released. The coating of the spheroid does not dissolve and may be found in the stools. Therefore, even if you notice spheroids in your stools, the full dose of the medicine has been absorbed.

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

Dizziness; headache; drowsiness
Insomnia
Nausea; dry mouth; constipation
Sweating (including night sweats)

Common (may affect up to 1 in 10 people)

Decreased appetite
Confusion; feeling detached from oneself; absence of orgasm; decreased libido; agitation; nervousness; abnormal dreams
Tremor; feeling restless or inability to sit still or remain motionless; tingling; altered taste sensation; 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)
Rapid heartbeat; palpitations
Increased blood pressure; hot flushes
Shortness of breath; yawning
Vomiting; diarrhea
Mild skin rash; itching
Increased frequency of urination; inability to urinate; difficulty passing urine
Menstrual irregularities such as increased bleeding or increased irregularity of bleeding; abnormal orgasm/ejaculation (males); erectile dysfunction (impotence)
Weakness (asthenia); fatigue; chills
Weight gain; weight loss
Increased cholesterol

Uncommon (may affect up to 1 in 100 people)

Hyperactivity, racing thoughts, and reduced need for sleep (mania)
Hallucinations; feeling detached from reality; abnormal orgasm; absence of sensations or emotions; feeling overexcited; teeth grinding
Fainting; involuntary muscle movements; impaired coordination and balance
Dizziness (especially when standing up too quickly); low blood pressure
Vomiting blood; black tarry stools or blood in the stools; which may indicate internal bleeding
Sensitivity to sunlight; bruising; abnormal hair loss
Urinary incontinence
Muscle stiffness, spasms, and involuntary movements
Slight changes in blood levels of liver enzymes

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

Seizures
Cough, wheezing, and shortness of breath, which may be accompanied by high temperature
Disorientation and confusion, often accompanied by hallucinations (delirium)
Excessive water intake (known as SIADH)
Decreased blood sodium levels
Severe eye pain and reduced or blurred vision
Abnormal, rapid, or irregular heartbeat, which may lead to fainting
Severe abdominal or back pain (which may indicate a serious problem with the intestine, liver, or pancreas)
Itching, yellow skin or eyes, dark urine, or flu-like symptoms, which are signs of liver inflammation (hepatitis)

Very rare (affects less than 1 in 10,000 people)

Prolonged bleeding, which may indicate a reduced number of platelets in the blood, leading to an increased risk of bruising or bleeding
Abnormal production of breast milk
Unexpected bleeding, for example bleeding gums, blood in urine or vomit, or unexpected bruising or broken blood vessels

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

Suicidal thoughts and suicidal behaviour: cases of suicidal thoughts and suicidal behaviour have been reported during treatment with venlafaxine or shortly after stopping venlafaxine treatment (see section 2, What you need to know before taking Ixilania)
Aggression
Dizziness
Heavy vaginal bleeding shortly after childbirth (postpartum haemorrhage); see Pregnancy and breastfeeding in section 2 for further information

Sometimes Ixilania causes side effects that you may not be aware of, such as increases in blood pressure or abnormal heartbeat; slight changes in blood levels of liver enzymes, sodium, or cholesterol. Less frequently, Ixilania may reduce the function of platelets in your blood, increasing the risk of bruising and bleeding.
Therefore, your doctor may wish to carry out occasional blood tests, particularly if you have been taking Ixilania for a long time.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, please inform your doctor or pharmacist. You can also report side effects directly via the national reporting system at
https://www.aifa.gov.it/web/guest/content/segnalazioni-reazioni-avverse. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Ixilania

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton. The expiry date refers to the last day of that month.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Ixilania contains
The active substance is venlafaxine.
Ixilania 75 mg:
One hard capsule contains:
Active substance: venlafaxine hydrochloride 84.9 mg equivalent to 75 mg venlafaxine base
Excipients: microcrystalline cellulose, povidone, talc, anhydrous colloidal silica, magnesium stearate, ethylcellulose, copovidone, black iron oxide (E172), red iron oxide (E172), titanium dioxide (E171), gelatin.
Ixilania 150 mg:
One hard capsule contains:
Active substance: venlafaxine hydrochloride 169.8 mg equivalent to 150 mg venlafaxine base.
Excipients: microcrystalline cellulose, povidone, talc, anhydrous colloidal silica, magnesium stearate, ethylcellulose, copovidone, brilliant blue (E133), allura red (E129), sunset yellow (E110), and titanium dioxide (E171), gelatin.

Description of the appearance of Ixilania and contents of the pack
Ixilania 75 mg is a hard gelatin capsule, peach / opaque peach in colour, size '1', with a thick and thin radial circular band on the body and a thick and thin radial circular band on the cap, both in red ink. The capsule is filled with 6 film-coated mini-tablets, white to off-white, round, biconvex, each containing 12.5 mg.
Ixilania 75 mg is available in packs containing 14 capsules.

Ixilania 150 mg is a hard gelatin capsule, dark orange / opaque dark orange in colour, size "0", with a thick and thin radial circular band on the body and a thick and thin radial circular band on the cap, both in white ink. The capsule is filled with 12 film-coated mini-tablets, white to off-white, round, biconvex, each containing 12.5 mg.
Ixilania 150 mg is available in packs containing 10 capsules.
Not all pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer
Marketing Authorization Holder
Neuraxpharm Italy S.p.A.
Via Piceno Aprutina, 47
63100 Ascoli Piceno (AP)
Italy

Manufacturer
PHARMADOX HEALTHCARE LTD
KW20A Kordin Industrial Park Paola PLA 3000, Malta

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