Document: leaflet MAH BRAND_PLPI 15833-0072 change

• leaflet MAH BRAND_PLPI 15833-0072
• leaflet MAH BRAND_PLPI 15833-0074

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Package leaflet - Information for the user

Sivion XL 225mg Prolonged-Release Tablets

Venlafaxine hydrochloride

What is in this leaflet:

1.    What Sivion XL is and what it is used for

2.    What you need to know before you take Sivion XL

3.    How to take Sivion XL

4.    Possible side effects

5.    How to store Sivion XL

6.    Contents of the pack and other information

1.    What Sivion XL is and what it is used for

Sivion XL is an antidepressant that belongs to a group of medicines called serotonin and norepinephrine reuptake inhibitors (SNRIs). This group of medicines is used to treat depression and other conditions such as anxiety disorders. It is thought that people who are depressed and/or anxious have lower levels of serotonin and noradrenaline in the brain. It is not fully understood how antidepressants work, but they may help by increasing the levels of serotonin and noradrenaline in the brain. Sivion XL is a treatment for adults with depression. Sivion XL is also a treatment for adults with the following anxiety disorders: generalised anxiety disorder, social anxiety disorder (fear or avoidance of social situations) and panic disorder (panic attacks). Treating depression or anxiety disorders properly is important to help you get better. If it is not treated, your condition may not go away and may become more serious and more difficult to treat.

2.    What you need to know before you take Sivion XL

Do not take Sivion XL

If you are allergic to venlafaxine or any of the other ingredients of this medicine (listed in section 6)

If you are also taking or have taken any time 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 Sivion XL, can cause serious or even life-threatening side effects. Also, you must wait at least 7 days after you stop taking Sivion XL before you take any MAOI (see also the sections entitled "Other medicines and Sivion XL" and the information in that section about “Serotonin syndrome").

Warnings and precautions

Talk to your doctor before taking Sivion XL

If you use other medicines that taken concomitantly with Sivion XL could increase the risk of developing serotonin syndrome (see the section "Other medicines and Sivion XL")

If you have a swallowing, stomach or intestinal disorder that reduces your ability to swallow or pass foods by normal bowel movements

If you have eye problems, such as certain kinds of glaucoma (increased pressure in the eye)

If you have a history of high blood pressure If you have a history of heart problems If you have a history of fits (seizures)

If you have a history of low sodium levels in your blood (hyponatraemia)

If you have a tendency to develop bruises or a tendency to bleed easily (history of bleeding disorders), or if you are taking other medicines that may increase the risk of bleeding e.g. warfarin (used to prevent blood clots)

If your cholesterol levels get higher

If you have a history of, or if someone in your family has had, mania or bipolar disorder (feeling over-excited or euphoric)

If you have a history of aggressive behaviour.

Sivion XL may cause a sensation of restlessness or an inability to sit or stand still during the first few weeks of treatment.

You should tell your doctor if this happens to you.

If any of these conditions apply to you, please talk with your doctor before taking Sivion XL.

Thoughts of suicide and worsening of your depression or feelings of anxiety

If you are depressed and/or have anxiety disorders, you can sometimes have thoughts of harming or killing yourself. These may be increased when you first start taking antidepressants, since these medicines all take time to work, usually about two weeks, but sometimes longer.

You may be more likely to think like this:

If you have previously had thoughts about killing yourself or harming yourself

If you are a young adult. Information from clinical trials has shown an increased risk of suicidal behaviour in young adults (less than 25 years old) with psychiatric conditions who were treated with an antidepressant.

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

You may find it helpful to tell a relative or close friend that you are depressed or have an anxiety disorder and ask them to read this leaflet. You might ask them to tell you if they think your depression or anxiety is getting worse, or if they are worried about changes in your behaviour.

Dry mouth

Dry mouth is reported in 10% of patients treated with venlafaxine. This may increase the risk of caries. Therefore, you should take special care in your dental hygiene.

Diabetes

Your blood glucose levels may be altered due to Sivion XL. Therefore, the dosages of your diabetes medicines may need to be adjusted.

Use in children and adolescents under 18 years of age

Sivion XL should normally not be used for children and adolescents under 18 years. Also, you should know that patients under 18 have an increased risk of side effects, such as suicide attempt, suicidal thoughts and hostility (predominantly aggression, oppositional behaviour and anger) when they take this class of medicines. Despite this, your doctor may prescribe this medicine for patients under 18 because he/she decides that this is in their best interests. If your doctor has prescribed Sivion XL for a patient under 18, and you want to discuss this, please go back to your doctor. You should inform your doctor if any of the symptoms listed above develop or worsen when patients under 18 are taking Sivion XL. Also, the long-term safety effects concerning growth, maturation and cognitive and behavioural development of Sivion XL in this age group has not yet been demonstrated.

Other medicines and Sivion XL

Tell your doctor or pharmacist if you are taking or have recently taken any other medicines.

Your doctor should decide whether you can take Sivion XL with other medicines.

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

Monoamine oxidase inhibitors which are used to treat depression or Parkinson's disease must not be taken with Sivion XL. Tell your doctor if you have taken these medicines within the last 14 days. (MAOIs: see the section “Before you take Sivion xL")

Serotonin syndrome:

Serotonin syndrome, a potentially life-threatening condition (see the section "Possible Side Effects"), may occur with venlafaxine treatment, particularly when taken with other medicines Examples of these medicines include:

Triptans (used for migraine)

Medicines to treat depression, for instance SNRI, SSRIs, tricyclics, or medicines containing lithium Medicines containing linezolid, an antibiotic (used to treat infections)

Medicines containing moclobemide, a reversible MAOI (used to treat depression)

Medicines containing sibutramine (used for weight loss)

Medicines containing tramadol (a pain-killer)

Medicines containing methylene blue (used to treat high levels of methaemoglobin in the blood)

Products containing St John's Wort (also called Hypericum perforatum, a natural or herbal remedy used to treat mild depression)

Products containing tryptophan (used for problems such as sleep and depression)

Antipsychotics (used to treat a disease with symptoms such as hearing, seeing or sensing things which are not there, mistaken beliefs, unusual suspiciousness, unclear reasoning and becoming withdrawn).

Signs and symptoms of serotonin syndrome may include a combination of the following: restlessness, hallucinations, loss of coordination, fast heart beat, increased body temperature, fast changes in blood pressure, overactive reflexes, diarrhoea, coma, nausea, vomiting.

In its most severe form, serotonin syndrome can resemble Neuroleptic Malignant Syndrome (NMS). Signs and symptoms of NMS may include a combination of fever, fast heart beat, sweating, severe muscle stiffness, confusion, increased muscle enzymes (determined by a blood test)

Tell your doctor immediately, or go to the casualty department at your nearest hospital if you think serotonin syndrome is happening to you.

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

Ketoconazole, Itraconazole, Voriconazole, Posaconazole (antifungal medicines)

Clarithromycin, telithromycin (antibiotics used to treat infections)

Atazanavir, indinavir, nelfinavir, ritonavir, saquinavir (used to treat HIV infection)

Haloperidol or risperidone (to treat psychiatric conditions)

Metoprolol (a beta blocker to treat high blood pressure and heart problems)

Sivion XL with food, drink and alcohol

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

You should avoid alcohol while you are taking Sivion XL.

Pregnancy, breast-feeding and fertility

Tell your doctor if you become pregnant, or you are trying to become pregnant. You should use Sivion XL only after discussing the potential benefits and the potential risks to your unborn child with your doctor.

Make sure your midwife and/or doctor knows you are on Sivion XL. When taken during pregnancy, similar drugs (SSRIs) may increase the risk of a serious condition in babies, called persistent pulmonary hypertension of the newborn (PPHN), making the baby breathe faster and appear bluish. These symptoms usually begin during the first 24 hours after the baby is born.

If this happens to your baby you should contact your midwife and/or doctor immediately.

If you are taking Sivion XL during pregnancy, let your midwife and/or doctor know, as your baby might have some symptoms when it is born. These symptoms usually begin during the first 24 hours after the baby is born. They include irritability, tremor, hypotonia, constant crying, sleeping difficulties and not feeding properly. If your baby has these symptoms when it is born and you are concerned, contact your doctor and/or midwife who will be able to advise you.

Venlafaxine passes into breast milk. There is a risk of an effect on the baby, which may cause symptoms such as crying, irritability and abnormal sleep patterns. Symptoms consistent with venlafaxine drug discontinuation can also occur after stopping breast-feeding. Therefore, you should discuss the matter with your doctor, and he/she will decide whether you should stop breast-feeding or stop the therapy with Sivion XL.

Driving and using machines

Do not drive or use any tools or machines until you know how Sivion XL affects you.

Important information about some of the ingredients of Sivion XL

This medicine contains lactose. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.

3.    How to take Sivion XL

Always take this medicine exactly as your doctor has told you. You should check with your doctor or pharmacist if you are not sure.

The usual recommended starting dose for treatment of depression, generalised anxiety disorder and social anxiety disorder is 75mg per day. The dose can be raised by your doctor gradually, and if needed, even up to a maximum dose of 375mg daily for depression. If you are being treated for panic disorder, your doctor will start with a lower dose (37.5mg) and then increase the dose gradually. The maximum dose for generalised anxiety disorder, social anxiety disorder and panic disorder is

^225mg/day.    (Continued overleaf)

Take Sivion XL at approximately the same time each day, either in the morning or in the evening. Tablets must be swallowed whole with fluid and not opened, crushed, chewed or dissolved.

Sivion XL should be taken with food.

If you have liver or kidney problems, talk to your doctor, since your dose of Sivion XL may need to be different.

Do not stop taking Sivion XL without talking to your doctor (see the section "If you stop taking Sivion XL")

If you take more Sivion XL than you should

Call your doctor or pharmacist immediately if you take more than the amount of Sivion XL prescribed by your doctor.

The symptoms of a possible overdose may include a rapid heart beat, changes in level of alertness (ranging from sleepiness to coma), blurred vision, seizures or fits, and vomiting.

If you forget to take Sivion XL

If you miss a dose, take it as soon as you remember. However, if it is time for your next dose, skip the missed dose and take only a single dose as usual. Do not take more than the daily amount of Sivion XL that has been prescribed for you in one day. If you stop taking Sivion XL

Do not stop taking your treatment or reduce the dose without the advice of your doctor even if you feel better. If your doctor thinks that you no longer need Sivion XL, he/she may ask you to reduce your dose slowly before stopping treatment altogether. Side effects are known to occur when people stop using Sivion XL, especially when Sivion XL is stopped suddenly or the dose is reduced too quickly. Some patients may experience symptoms such as tiredness, dizziness, light headedness, headache, sleeplessness, sensation that everything around you is spinning or moving (vertigo), nightmares, dry mouth, loss of appetite, nausea, diarrhoea, nervousness, agitation, confusion, ringing in the ears, tingling or rarely electric shock sensations, weakness, sweating, seizures, or flu-like symptoms.

Your doctor will advise you on how you should gradually discontinue Sivion XL treatment. If you experience any of these or other symptoms that are troublesome, ask your doctor for further advice.

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

4. Possible side effects

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

Do not be concerned if you see a tablet in your stools after taking Sivion XL. As the tablet travels the length of your gastrointestinal tract, venlafaxine is slowly released. The shape of the tablet remains undissolved and is eliminated in your stools. Therefore, even though you may see a tablet in your stools, your dose of venlafaxine has been absorbed.

Allergic reactions

If any of the following happen, do not take more Sivion XL. Tell your doctor immediately, or go to the casualty department at your nearest hospital:

Chest tightness, wheezing, trouble swallowing or breathing Swelling of the face, throat, hands or feet

Feeling nervous or anxious, dizziness, throbbing sensations, sudden reddening of the skin and/or a warm feeling Severe rash, itching, or hives (elevated patches of red or pale skin that often itch)

Signs and symptoms of serotonin syndrome which may include restlessness, hallucinations, loss of coordination, fast heart beat, increased body temperature, fast changes in blood pressure, overactive reflexes, diarrhoea, coma, nausea, vomiting.

In its most severe form, serotonin syndrome can resemble Neuroleptic Malignant Syndrome (NMS). Signs and symptoms of NMS may include a combination of fever, fast heart beat, sweating, severe muscle stiffness, confusion, increased muscle enzymes (determined by a blood test).

Other side effects that you should tell your doctor about include:

Coughing, wheezing, shortness of breath and a high temperature Black (tarry) stools or blood in stools

Yellow skin or eyes, itchiness or dark urine, which may be symptoms of inflammation of the liver (hepatitis)

Heart problems, such as fast or irregular heart rate, increased blood pressure Eye problems, such as blurred vision, dilated pupils

Nerve problems, such as dizziness, pins and needles, movement disorder, seizures or fits Psychiatric problems, such as hyperactivity and euphoria (feeling unusually overexcited)

Withdrawal effects (see the section “How to take Sivion XL, if you stop taking Sivion XL")

Prolonged bleeding - if you cut or injure yourself, it may take slightly longer than usual for bleeding to stop.

Complete side effect listing

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

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

Common (may affect up to 1 in 10 people)

Appetite decreased

Confusion; feeling separated (or detached) from yourself; lack of orgasm; decreased libido; nervousness; insomnia; abnormal dreams

Drowsiness; tremor; pins and needles; increased muscle tonus

Visual disturbance including blurred vision; dilated pupils; inabiity of the eye to automatically change focus from distant

to near objects

Ringing in the ears (tinnitus)

Palpitations

Increase in blood pressure; flushing Yawning

Vomiting; constipation; diarrhoea

Increased frequency in urination; difficulties passing urine

Menstrual irregularities such as increased bleeding or increased irregular bleeding; abnormal ejaculation/orgasm (males); erectile dysfunction (impotence)

Weakness (asthenia); fatigue; chills Increased cholesterol

Uncommon (may affect up to 1 in 100 people)

Hallucinations; feeling separated (or detached) from reality; agitation; abnormal orgasm (females); lack of feeling or emotion; feeling over-excited; grinding of the teeth

A sensation of restlessness or an inability to sit or stand still; fainting; involuntary movements of the muscles; impaired

coordination and balance; altered taste sensation

Fast heartbeat; feeling dizzy (particulary when standing up too quickly)

Vomiting blood; black tarry stools (faeces) or blood in stools; which can be a sign of internal bleeding General swelling of the skin especially the face, mouth, tongue, throat area or hands and feet and/or a raised itchy rash (hives) may be present; sensitivity to sunlight; bruising; rash; abnormal hair loss Inability to pass urine Weight gain; weight loss Rare (may affect up to 1 in 1,000 people)

Seizures or fits Inability to control urination

Over activity, racing thoughts and decreased need for sleep (mania)

Not known (frequency cannot be estimated from the available data)

Reduced number of platelets in your blood, leading to an increased risk of bruising or bleeding; blood disorders which may l ead to an increased risk of infection

Swollen face or tongue, shortness of breath or difficulty breathing, often with skin rashes ( this may be a serious allergic reaction)

Excessive water intake (known as SIADH)

Decrease in blood sodium levels

Suicidal ideation and suicidal behaviours; cases of suicidal ideation and suicidal behaviours have been reported during venlafaxine therapy or early after treatment discontinuation (see section 2, “Before you take Sivion XL")

Disorientation and confusion often accompanied by hallucination (delirium); aggression

A high temperature with rigid muscles, confusion or agitation, and sweating, or if you experience jerky muscle movements which you can't control, these may be symptoms of serious conditions known as neuroleptic malignant syndrome; euphoric feelings, drowsiness, sustained rapid eye movement, clumsiness, restlessness, feeling of being drunk, sweating or rigid muscles, which are symptoms of serotonin syndrome; stiffness, spasms and involuntary movements of the muscles

Severe eye pain and decreased or blurred vision Vertigo

Decrease in blood pressure; abnormal, rapid or irregular heart beat, which could lead to fainting; unexpected bleeding, e.g. bleeding gums, blood in the urine or in vomit, or the appearance of unexpected bruises or broken blood vessels (broken veins)

Coughing, wheezing, shortness of breath and a high temperature, which are symptoms of inflammation of the lungs associated with an increase in white blood cells (pulmonary eosinophilia)

Severe abdominal or back pains (which could indicate a serious problem in the gut, liver or pancreas)

Itchiness, yellow skin or eyes, dark urine, or flu-like symptoms, which are symptoms of inflammation of the liver (hepatitis); slight changes in blood levels of liver enzymes

Skin rash, which may lead to severe blistering and peeling of the skin; itching; mild rash Unexplained muscle pain, tenderness or weakness (rhabdomyolysis)

Abnormal breast milk production

Sivion XL sometimes causes unwanted effects that you may not be aware of, such as increases in blood pressure or abnormal heart beat; slight changes in blood levels or liver enzymes, sodium or cholesterol. More rarely, Sivion XL may reduce the function of platelets in your blood, leading to an increased risk of bruising or bleeding. Therefore, your doctor may wish to do blood tests occasionally, particularly if you have been taking Sivion XL for a long time.

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Yellow Card Scheme at www.mhra.gov.uk/yellowcard. By reporting side effects, you can provide more information on the safety of this medicine.

5. How to store Sivion XL

Keep out of the sight and reach of children.

Do not use Sivion XL after the expiry date which is stated on the packaging.

The expiry date refers to the last day of that month.

Do not store above 30°C. Store in the original package in order 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 required. These measures will help to protect the environment.

Do not use if any signs of deterioration are seen.

6. Contents of the pack and other information

What Sivion XL contains

The active substance is venlafaxine.

Each prolonged-release tablet contains 225mg venlafaxine (as hydrochloride).

The other ingredients are

Core: mannitol (E421), povidone K-90, macrogol 400, cellulose microcrystalline, colloidal anhydrous silica, magnesium stearate.

Coat: cellulose acetate, macrogol 400, hypromellose, lactose monohydrate, titanium dioxide (E171), triacetin.

What Sivion XL looks like and contents of the pack

White round tablets, plain on one side with a laser hole on the reverse.

Sivion XL is available in pack sizes of 14 or 30 tablets.

PL holder:

Manx Pharma Ltd, Taylor Group House, Wedgnock Lane, Warwick, CV34 5YA, UK PL 15833/0072 and PL 15833/0074    | POM |

Procured from within the EU.

Manufacturer:

Laboratorios LICONSA S.A, Avada.

Miralcampo, No 7, Poligono Industrial Miralcampo 19200 Azuqueca de Henares (Guadalajara), SPAIN

To request a copy of this leaflet in large print, audio or Braille please call 01926 482511

This leaflet was last revised on 7/1/16

WIP URN		070116-XXXX-PIL-02
APPROVED URN
Job		Sivion XL PIL - Italy + Greece - Side 2
Size		540 x 140mm
Date		7 January 2016
BOH Approval Date
Saved as		14166/02 PIL S2.ai M1X
Prints		1 Colour - Black