Document: leaflet MAH GENERIC_PL 00289-0874 change

• leaflet CONSILIENT HEALTH_PL 01656-0036
• leaflet MAH GENERIC_PL 00289-0874
• leaflet MAH GENERIC_PL 01656-0036
• leaflet MAH GENERIC_PL 20532-0163
• leaflet NICHE GENERICS_PL 01656-0036

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Mirtazapine 15, 30 & 45 mg Orodispersible Tablets

Mirtazapine

Read all of this leaflet carefully before you start 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 you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.

•    If you get any of the side effects talk to your doctor or pharmacist.This includes any possible side effects not listed in this leaflet. See section 4.

1.    What Mirtazapine is and what it is used for

2.    What you need to know before you take Mirtazapine

3.    How to take Mirtazapine

4.    Possible side effects

5.    How to store Mirtazapine

6.    Content of the pack and other information

What Mirtazapine is and what it is used for

•    Mirtazapine is one of a group of medicines called antidepressants

•    Mirtazapine is used to treat depressive illness in adults.

•    You must talk to a doctor if you do not feel better of if you feel worse.

^2 What you need to know before you take Mirtazapine Do not take Mirtazapine:

•    If you are allergic to mirtazapine or any of the other ingredients of this medicine (listed in section 6). If so, you must talk to your doctor as soon as you can before taking Mirtazapine.

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

Warnings and precautions

Talk to your doctor or pharmacist before taking Mirtazapine.

Thoughts of suicide and worsening of your depression

If you are depressed you can sometimes have thoughts of harming or killing yourselfThese 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.

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

Ybu 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 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 be 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.

-    certain kinds of heart conditions that may change your heart rhythm, a recent heart attack, heart failure, or take certain medicines that may affect the heart's rhythm

•    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.

Children and adolescents

Mirtazapine should normally not be used for children and adolescents under 18 years because efficacy 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.

Other medicines and Mirtazapine

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

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), methylene blue (used to treat high levels of methemoglobin in the blood) 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 and 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 HIV protease 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 or 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 I 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.

•    Medicines that may affect the heart's rhythm such as certain antibiotics and some antipsychotics. Mirtazapine with food, drink and alcohol

" 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 with or without food.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this 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 use Mirtazapine until, or shortly before birth, your baby should be supervised for possible adverse effects.

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 can affect your concentration or alertness. Make sure these abilities are not affected before you drive or operate machinery. If your doctor has prescribed Mirtazapine for a patient under 18 years make sure the concentration and alertness is not affected before participation in traffic (eg. on bicycle). Mirtazapine contains aspartame:

Aspartame contains a source of phenylalanine. May be harmful for people with phenylketonuria.

"3    How to take Mirtazapine

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

The recommended dose is between 15 mg and 45 mg

The usual starting dose is 15 mg 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 • Take Mirtazapine at the same time each day.

It is best to take Mirtazapine as a single dose before you go to bed. However your doctor may suggest to split your dose of Mirtazapine - 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 the orodispersible tablets as follows

Take your tablets orally.

•    Do not crush the orodispersible tablet: in order to prevent crushing the orodispersible tablet, do not push against the tablet pocket

•    Tear off one tablet pocket.

Each blister contains six tablet pockets, which are separated by perforations. Tear off one tablet pocket along the dotted lines (Figure 1): • Peel off the lid.

Carefully peel off the lidding foil, starting in the corner indicated by the arrow (Figures 2):

• Take out the orodispersible tablet with dry hands (Figure 3) and place it on the tongue. It will rapidly disintegrate and can be swallowed with or without water.

When can you expect to start feeling better

Usually Mirtazapine 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:

•    2 to 4 weeks after you have started taking Mirtazapine, 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 until your symptoms of depression have disappeared for 4 to 6 months.

If you take more Mirtazapine than you should

•    If you (or someone else) have taken too much Mirtazapine, call a doctor straight away. The most likely signs of an overdose of Mirtazapine (without other medicines or alcohol) are drcwsiness, disorientation and increased heart rate.The symptoms of a possible overdose may include changes to your heart rhythm (fast, irregular heartbeat) and/or fainting which could be symptoms of a life-threatening condition known asTorsade de Pointes.

If you forget to take Mirtazapine

If you are supposed to take your dose once a day:

•    Do not take a double dose to make up for a forgotten 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

•    Only stop taking Mirtazapine 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, even when your depression has lifted. If you suddenly stop taking Mirtazapine 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 medicine, ask your doctor or pharmacist.

Possible side effects

Stop taking Mirtazapine and tell your doctor straight away if you develop any of the following side effects:

•    Feeling elated or emotionally 'high' (mania).

•    Yellow colouring of eyes or skin; this may suggest disturbance in liver function (jaundice).

•    Signs of infection such as sudden unexplainable high fever, sore throat and mouth ulcers (agranulocytosis). Your doctor should order 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 anaemia), a shortage of blood platelets (thrombocytopenia) or an increase in the number of white blood cells (eosinophilia).

•    Epileptic attack (convulsions).

•    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.

•    Thoughts of harming or killing yourself. Contact your doctor or go to a hospital straight away.

•    Stevens Johnsons syndrome andToxic epidermal necrolysis - very rare but very serious side effects. If you experience any of the following side effects tell your doctor or nurse straight away:

•    skin peeling

•    sores on the mucous membranes

•    skin rash,

Other possible side effects

Other possible side effects of Mirtazapine are listed below. Some side effects are more likely to occur than others:

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

•    Increase in appetite and weight gain

•    Drowsiness or sleepiness, headache

•    Dry mouth.

Common (may affect up to 1 in 10 people):

•    Lethargy, dizziness, shakiness or tremor, tiredness

•    Nausea, diarrhoea, vomiting, constipation

•    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)

•    Vivid dreams, confusion, feeling anxious, sleeping problems.

Uncommon (may affect upto 1 in 100 people):

•    Abnormal sensation in the skin eg. burning, stinging, tickling or tingling (paraesthesia), restless legs, urge to move, fainting (syncope)

•    Sensations of numbness in the mouth (oral hypoaesthesia)

•    Low blood pressure

•    Nightmares, feeling agitated, hallucinations Rare (may affect up to 1 in 1,000 people):

•    Muscle twitching or contractions (myoclonus)

•    Aggression

•    Inflammation of the pancreas

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

•    Erythema multiforme, a skin disease characterised by itchy pink-red blotches starting on your feet and hands

•    Blisters full of fluid (dermatitis bullous)

•    Increased salivation

•    Sleep walking

•    Distorted speech (dysarthria)

•    Abnormal sensations in the mouth (oral paraesthesia)

•    Swelling in the mouth (mouth oedema)

•    Swelling throughout the body (generalized oedema)

•    Localized swelling

•    Hyponatraemia

•    Inappropriate anti-diuretic hormone secretion

•    Difficulty passing urine

•    Increase in creatine kinase blood levels in the body

•    Muscle pain, tenderness, weakness and swelling of the affected muscles and darkening or discolouration of the urine (rhabdomyolysis)

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

Additional side effects in children and adolescents

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

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 theYellow Card Scheme at: www.mhra.gov.uk/yellowcard. By reporting side effects you can help provide more information on the safety of this medicine.

[5 How to store Mirtazapine

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the carton after EXP The expiry date refers to the last day of that month.

This medicinal product does not require any special storage conditions. Do not transfer to another container.

Do not throw away any medicine via wastewater or household waste. Ask your pharmacist how to throw away of medicines you no longer use. These measures will help to protect the environment.

^6 Contents of the pack and other information

What Mirtazapine contains

•    The active substance is mirtazapine. Each tablet contains 15, 30 or 45 mg mirtazapine.

•    The other ingredients are xylitol, precipitated silica, basic butylated methacrylate copolymer, crospovidone, aspartame, orange flavour, mannitol, magnesium stearate.

What Mirtazapine looks like and contents of the pack

•    The 15 mg tablets are round, white, bevelled edge tablets marked with number "93" on one side and with number "7303" on the other.

•    The 30 mg tablets are round, white, bevelled edge tablets marked with number "93" on one side and with number "7304" on the other

•    The 45 mg tablets are round, white, bevelled edge tablets marked with number "93" on one side and with number "7305" on the other

•    The 15 mg tablets are available in pack sizes of 6, 12, 18, 28, 30, 48, 50, 60, 90, 96, 100, 200 and 500 tablets.

•    The 30 mg tablets are available in pack sizes of 6, 12, 18, 28, 30, 48, 50, 60, 90, 96, 100, 180, 200 and 500 tablets.

•    The 45 mg tablets are available in pack sizes of 18, 28, 30, 48, 50, 60, 90, 96, 100, 180, 200 and 500 tablets.

•    Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

The Marketing Authorisation holder and the company responsible for manufacture is TEVA UK Limited,

Eastbourne, BN22 9AG.

This leaflet was last approved in June 2015

PL 00289/0874-0876

84791-ZC