Document: leaflet MAH GENERIC_PL 21880-0055 change

• leaflet MAH GENERIC_PL 21880-0055
• leaflet MAH GENERIC_PL 28444-0099
• leaflet MAH GENERIC_PL 44041-0025

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•    low blood pressure

•    nightmares

•    feeling agitated

•    hallucinations

•    urge to move Rare:

•    yellow colouring of eyes or skin; this may suggest disturbance in liver function (jaundice) Stop taking Mirtazapine and tell your doctor straight away.

•    muscle twitching or contractions (myoclonus)

•    aggression

•    pancreatitis which can casus a severe dull pain around the top of your stomach which may move along your back sometimes with feeling and being sick, diarrhea, loss of appetite, high temperature and tenderness of the abdomen (stomach)

Not known:

•    signs of infection such as sudden unexplainable high fever, sore throat and mouth ulcers (agranulocytosis)

Stop taking Mirtazapine and contact your doctor straight away for a blood test.

In rare cases Mirtazapine can cause disturbances in the production of blood cells (bone marrow depression). Some people become less resistant to infection because Mirtazapine can cause a temporary shortage of white blood cells (granulocytopenia). In rare cases Mirtazapine can also cause a shortage of red and white blood cells, as well as blood platelets (aplastic anemia), a shortage of blood platelets (thrombocytopenia) or an increase in the number of white blood cells (eosinophilia).

•    epileptic attack (convulsions)

Stop taking Mirtazapine and tell your doctor straight away.

•    a combination of symptoms such as inexplicable fever, sweating, increased heart rate, diarrhoea, (uncontrollable) muscle contractions, shivering, overactive reflexes, restlessness, mood changes and unconsciousness. In very rare cases these can be signs of serotonin syndrome.

Stop taking Mirtazapine and tell your doctor straight away.

•    thoughts of harming or killing yourself

Contact your doctor or go to a hospital straight away.

•    abnormal sensations in the mouth (oral paraesthesia)

•    difficulty speaking clearly

•    swelling in the mouth (mouth oedema) or elsewhere in your body (local and general oedema)

•    an increase in saliva production

•    sleep walking

•    hyponatraemia

•    inappropriate anti-diuretic hormone secretion

•    Severe reactions to this medicine include rash, blisters or peeling skin which keep getting worse. Stop taking Mirtazapine and tell your doctor straight away.

If any of the side effects gets serious or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

5)    How to store Mirtazapine tablets

Keep out of the reach and sight of children.

This medicinal product does not require any special storage conditions.

Store in the original package.

Do not use Mirtazapine tablets after the expiry date, which is stated on the carton. The expiry date refers to the last day of that month.

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.

6)    Further information

What Mirtazapine tablets contain

The active ingredient is Mirtazapine. Each film coated tablet contains 15, 30 or 45 mg Mirtazapine.

- The other ingredients are lactose monohydrate, maize starch, hydroxypropyl cellulose, low substituted hydroxypropyl cellulose, magnesium stearate (E470b), silica colloidal anhydrous, hypromellose (E464) and titanium dioxide (E 171).

The 15 mg tablets also contain yellow iron oxide (E 172).

The 30 mg tablets also contain yellow iron oxide (E172), red iron oxide (E172) and black iron oxide (E172).

What Mirtazapine tablets look like and contents of the pack

Mirtazapine 15 mg tablets are yellow, biconvex, capsule shaped film coated tablets with score line on one side and 15 debossed on other side.

Mirtazapine 30 mg tablets are reddish brown, biconvex, capsule shaped film coated tablets with score line on one side and 30 debossed on other side.

Mirtazapine 45 mg tablets are white, biconvex, capsule shaped film coated tablets plain on one side and 45 debossed on other side.

Mirtazapine 15, 30 and 45 mg tablets are available in PVC coated PVdC blister packs of 10/14/ 28/30/40/50/56/60/70/84/90/100/200/250/500 tablets. Not all packs may be marketed.

15mg: PL No.: 21880/0053 30mg: PL No.: 21880/0054 45mg: PL No.: 21880/0055 This leaflet was last revised in 04/2013

MA Holder:

MEDREICH PLC

Warwick House, Plane Tree Crescent,

Feltham TW13 7HF, UK

E-mail : info@medreich.co.uk    121XXXX

PACKAGE LEAFLET: INFORMATION FOR THE USER

Mirtazapine 15, 30 & 45 mg tablets

(Mirtazapine)

Read all of this leaflet carefully before you start taking this medicine.

-    Keep this leaflet. You may need to read it again.

-    If you have any further questions, ask your doctor or pharmacist.

-    This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.

-    If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

In this leaflet:

1)    What Mirtazapine tablet is and what it is used for

2)    Before you take Mirtazapine tablets

3)    How to take Mirtazapine tablets

4)    Possible side effects

5)    How to store Mirtazapine tablets

6)    Further information

1)    What Mirtazapine tablets are and what they are used for

Mirtazapine is one of a group of medicines called antidepressants.

Mirtazapine tablets are used to treat depressive illness.

2)    Before you take Mirtazapine tablets Do not take Mirtazapine tablets

•    if you are allergic (hypersensitive) to Mirtazapine or any of the other ingredients of Mirtazapine tablets. If so, you must talk to your doctor as soon as you can before taking Mirtazapine tablets.

•    if you are taking or have recently taken (within the last two weeks) medicines called monoamine oxidase inhibitors (MAO-Is).

Take special care with Mirtazapine

Use in children and adolescents under 18 years of age

Mirtazapine should normally not be used for children and adolescents under 18 years because efficiency was not demonstrated. 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 Mirtazapine for patients under 18 because he/she decides that this is in their best interests. If your doctor has prescribed Mirtazapine 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 Mirtazapine. Also, the long-term safety effects concerning growth, maturation and cognitive and behavioural development of Mirtazapine in this age group have not yet been demonstrated. In addition, significant weight gain has been observed in this age category more often when treated with Mirtazapine compared with Adults.

Thoughts of suicide and worsening of your depression

If you are depressed you can sometimes have thoughts of harming or killing yourself. These may be increased when first starting 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 or harming yourself.

•    if you are a young adult. Information from clinical trials has shown an increased risk of suicidal behaviour in adults aged less than 25 years 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, and ask them to read this leaflet. You might ask them to tell you if they think your depression is getting worse, or if they are worried about changes in your behaviour.

Also take special care with Mirtazapine

•    if you have, or have ever had one of the following conditions.

Tell your doctor about these conditions before taking Mirtazapine, if not done previously.

-    seizures (epilepsy). If you develop seizures or your seizures become more frequent, stop taking Mirtazapine and contact your doctor immediately;

-    liver disease, including jaundice. If jaundice occurs, stop taking Mirtazapine and contact your doctor immediately;

-    kidney disease;

-    heart disease, or low blood pressure;

-    schizophrenia. If psychotic symptoms, such as paranoid thoughts become more frequent or severe, contact your doctor straight away;

-    manic depression (alternating periods of feeling elated/overactivity and depressed mood).

If you start feeling elated or over-excited, stop taking Mirtazapine and contact your doctor immediately;

-    diabetes (you may need to adjust your dose of insulin or other antidiabetic medicines);

-    eye disease, such as increased pressure in the eye (glaucoma);

-    difficulty in passing water (urinating), which might be caused by an enlarged prostate.

•    if you develop signs of infection such as inexplicable high fever, sore throat and mouth ulcers.

Stop taking Mirtazapine and consult your doctor immediately for a blood test.

In rare cases these symptoms can be signs of disturbances in blood cell production in the bone marrow. While rare, these symptoms most commonly appear after 4-6 weeks of treatment.

•    if you are an elderly person. You could be more sensitive to the side-effects of antidepressants.

Taking other medicines

Tell your doctor or pharmacist if you are taking (or plan to take) any of the medicines in the

following list.

Please also tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.

Do not take Mirtazapine in combination with:

•    monoamine oxidase inhibitors (MAO inhibitors). Also, do not take Mirtazapine during the two weeks after you have stopped taking MAO inhibitors. If you stop taking Mirtazapine, do not take MAO inhibitors during the next two weeks either.

Examples of MAO inhibitors are moclobemide, tranylcypromine (both are antidepressants) and selegiline (used for Parkinson's disease).

Take care when taking Mirtazapine in combination with:

•    antidepressants such as SSRIs, venlafaxine and L-tryptophan, or triptans (used to treat migraine), tramadol (a pain-killer), linezolid (an antibiotic), lithium (used to treat some psychiatric conditions) and St. John's Wort - Hypericum perforatum preparations

(a herbal remedy for depression). In very rare cases Mirtazapine alone or the combination of Mirtazapine with these medicines, can lead to a so-called serotonin syndrome. Some of the symptoms of this syndrome are: inexplicable fever, sweating, increased heart rate, diarrhoea, (uncontrollable) muscle contractions, shivering, overactive reflexes, restlessness, mood changes, and unconsciousness. If you get a combination of these symptoms, talk to your doctor immediately.

•    the antidepressant nefazodone. It can increase the amount of Mirtazapine in your blood. Inform your doctor if you are using this medicine. It might be needed to lower the dose of Mirtazapine, or when use of nefazodone is stopped, to increase the dose of Mirtazapine again.

•    medicines for anxiety or insomnia such as benzodiazepines; medicines for schizophrenia such as olanzapine; medicines for allergies such as cetirizine;

medicines for severe pain such as morphine.

In combination with these medicines Mirtazapine can increase the drowsiness caused by these medicines.

•    medicines for infections; medicines for bacterial infections (such as erythromycin); medicines for fungal infections (such as ketoconazole) and medicines for HIV/AIDS (such as HIVprotease inhibitors).

In combination with Mirtazapine these medicines can increase the amount of Mirtazapine in your blood. Inform your doctor if you are using these medicines. It might be needed to lower the dose of Mirtazapine, or when these medicines are stopped, to increase the dose of Mirtazapine again.

•    medicines for epilepsy such as carbamazepine and phenytoin; medicines for tuberculosis such as rifampicin.

In combination with Mirtazapine these medicines can reduce the amount of Mirtazapine in your blood. Inform your doctor if you are using these medicines. It might be needed to increase the dose of Mirtazapine, or when these medicines are stopped to lower the dose of Mirtazapine again.

•    medicines to prevent blood clotting such as warfarin.

Mirtazapine can increase the effects of warfarin on the blood. Inform your doctor if you are using this medicine. In case of combination it is advised that a doctor monitors your blood carefully.

Taking Mirtazapine tablets with food and drink

You may get drowsy if you drink alcohol while you are taking Mirtazapine.

You are advised not to drink any alcohol.

You can take Mirtazapine tablets with or without food.

Pregnancy and breast feeding

Ask your doctor or pharmacist for advice before taking any medicine.

Limited experience with Mirtazapine administration to pregnant women does not indicate an increased risk. However, caution should be exercised when used during pregnancy.

If you are taking Mirtazapine tablets and you become pregnant or you plan to get pregnant, ask your doctor whether you may continue taking Mirtazapine tablets. If you use Mirtazapine tablets until, or shortly before birth, your baby should be supervised for possible adverse effects. Ask your doctor whether you can breast-feed, while taking Mirtazapine tablets.

Make sure your midwife and/or doctor knows you are on Mirtazapine. 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. Driving and using machines

Mirtazapine tablets can affect your concentration or alertness. Make sure these abilities are not affected before you drive or operate machinery.

Important information about some of the ingredients of Mirtazapine tablets

Mirtazapine film-coated tablet 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 Mirtazapine tablets

Always take Mirtazapine tablets exactly as your doctor or pharmacist tells you to. You should check with your doctor or pharmacist if you are not sure.

How much to take

The usual starting dose is 15 or 30 mg every day. Your doctor may advise you to increase your dose after a few days to the amount that is best for you (between 15 and 45 mg per day). The dose is usually the same for all ages. However, if you are an elderly person or if you have renal or liver disease, your doctor may adapt the dose.

When to take Mirtazapine tablets

Take Mirtazapine tablets at the same time each day.

It is best to take Mirtazapine tablets as a single dose before you go to bed. However your doctor may suggest to split your dose of Mirtazapine tablets - once in the morning and once at night time before you go to bed. The higher dose should be taken before you go to bed.

Take your tablets orally. Swallow your prescribed dose of Mirtazapine tablets without chewing, with some water or juice.

When can you expect to start feeling better

Usually Mirtazapine tablets will start working after 1 to 2 weeks and after 2 to 4 weeks you may start to feel better.

It is important that, during the first few weeks of the treatment, you talk with your doctor about the effects of Mirtazapine tablets:

2 to 4 weeks after you have started taking Mirtazapine tablets, talk to your doctor about how this medicine has affected you.

If you still don't feel better, your doctor may prescribe a higher dose. In that case, talk to your doctor again after another 2 to 4 weeks. Usually you will need to take Mirtazapine tablets until your symptoms of depression have disappeared for 4 to 6 months.

If you take more Mirtazapine tablets than you should

If you or someone else have taken too much Mirtazapine tablets, call a doctor straight away. The most likely signs of an overdose of Mirtazapine tablets (without other medicines or alcohol) are drowsiness, disorientation and increased heart rate.

If you forget to take Mirtazapine tablets

If you are supposed to take your dose once a day

•    If you have forgotten to take your dose of Mirtazapine tablets, do not take the missed dose.

Just skip it. Take your next dose at the normal time.

If you are supposed to take your dose twice a day

•    if you have forgotten to take your morning dose, simply take it together with your evening dose.

•    if you have forgotten to take your evening dose, do not take it with the next morning dose; just skip it and continue with your normal morning and evening doses.

•    if you have forgotten to take both doses, do not attempt to make up for the missed doses. Skip both doses and continue the next day with your normal morning and evening doses.

If you stop taking Mirtazapine tablets

Only stop taking Mirtazapine tablets in consultation with your doctor.

If you stop too early, your depression might come back. Once you are feeling better, talk to your doctor. Your doctor will decide when treatment can be stopped.

Do not suddenly stop taking Mirtazapine tablets, even when your depression has lifted. If you suddenly stop taking Mirtazapine tablets you may feel sick, dizzy, agitated or anxious, and have headaches. These symptoms can be avoided by stopping gradually. Your doctor will tell you how to decrease the dose gradually.

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

4) Possible side effects

Like all medicines, Mirtazapine tablets can cause side effects, although not everybody gets these side effects.

Some side effects are more likely to occur than others. The possible side effects of Mirtazapine are listed below: and can be divided as:

•    Very common: affects more than 1 user in 10

•    Common: affects 1 to 10 users in 100

•    Uncommon: affects 1 to 10 users in 1,000

•    Rare: affects 1 to 10 users in 10,000

•    Very rare: affects less than 1 user in 10,000

•    Not known: cannot be estimated from the available data Very common:

•    increase in appetite and weight gain

•    drowsiness or sleepiness

•    headache

•    dry mouth

Common:

•    lethargy

•    dizziness

•    shakiness or tremor

•    nausea

•    diarrhoea

•    vomiting

•    rash or skin eruptions (exanthema)

•    pain in your joints (arthralgia) or muscles (myalgia)

•    back pain

•    feeling dizzy or faint when you stand up suddenly (orthostatic hypotension)

•    swelling (typically in ankles or feet) caused by fluid retention (oedema)

•    tiredness

•    vivid dreams

•    confusion

•    feeling anxious

•    sleeping problems

In children under 18 years the following adverse events were observed commonly in clinical trials: significant weight gain, hives and increased blood triglycerides.

Uncommon:

•    feeling elated or emotionally 'high' (mania)

Stop taking Mirtazapine and tell your doctor straight away.

•    abnormal sensation in the skin e.g. burning, stinging, tickling or tingling (paraesthesia)

•    restless legs

•    fainting (syncope)