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 side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet

1.    What Misyo is and what it is used for

2.    What you need to know before you take Misyo

3.    How to take Misyo

4.    Possible side effects

5.    How to store Misyo

6.    Contents of the pack and other information

1.    What Misyo is and what it is used for

This medicine contains methadone hydrochloride, which belongs to a group of medicines called narcotic analgesics. It is used in the treatment of addiction in order to reduce withdrawal symptoms.

All patients receiving Misyo must be routinely monitored for signs of misuse, abuse and addiction during treatment.

2.    What you need to know before you take Misyo Do not take Misyo, if:

-    you are allergic (hypersensitive) to methadone or to any of the other ingredients of this medicine (listed in section 6). An allergic reaction includes a rash, itching or shortness of breath;

-    you are having an asthma attack (you should not use this medicine during an asthma attack. If you give this medicine to yourself (self-administration), wait until the asthma attack has passed and you are fully recovered;

-    you are addicted to alcohol;

-    you are taking monoamino oxidase inhibitors (MAOIs) used to treat depression or if you have taken MAOI medicine in the past two weeks (See "Taking other medicines");

-    you are not dependent on opioid drugs;

-    you have heart problems (QT prolongation);

-    you have severe liver problems;

-    you are in labour.

If you are not sure if any of the above applies to you, talk to your doctor or pharmacist before taking Misyo.

Warnings and precautions

Talk to your doctor or pharmacist before taking Misyo if you:

-    have severe breathing problems;

-    have or have recently had a head injury;

-    have liver or kidney problems;

-    have epilepsy;

-    have low thyroid function (hypothyroid);

-    have problems with your adrenal glands;

-    have an enlarged prostate gland;

-    have low blood pressure;

-    are in shock;

-    have a muscle weakness disease called myasthenia gravis;

-    have bowel problems;

-    have recognized risk factors for QT prolongation they are:

-    have a history of irregular heart beat;

-    have a history of heart disease;

-    have a family history of people dying suddenly without cause;

-    have low potassium, sodium or magnesium levels;

-    are pregnant or breast-feeding;

-    are extremely ill or an older person. You may more sensitive to the medicine. If you are not sure if any of the above applies to you, talk to your doctor or pharmacist before taking Misyo.

Other medicines and Misyo

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

Methadone hydrochloride can affect the way some other medicines work. Also some medicines can affect the way it works.

You must not take Misyo:

-    at the same time or within 2 weeks of taking monoamino oxidase inhibitors (MAOIs).

In particular, tell your doctor if you are taking any of the following medicines:

-    other opiate analgesics;

-    medicines that have effect on your mental state (e.g. thioridazine, phenothiazines, haloperidol and sertindole);

-    medicines for heart problems such as verapamil and quinidine;

-    medicine to treat depression (desipramine, nefazodone, fluvoxamine, fluoxetine, paroxetine and sertraline);

-    anti-inflammatory and immunosuppressant's (e.g. dexamethasone and ciclosporin);

-    antiviral drugs including some medicine used to treat HIV (nevirapine, zidovudine, efavirenz, nelfinavir, ritonavir, amprenavir, delavirdine, lopinavir/ ritonavir, ritonavir/saquinavir, abacavir, didanosine and stavudine);

-    antibiotics (medicines used to treat bacterial infections) such as ciprofloxacin and macrolilide antibiotics for example clarithromycin, telithromycin and erythromycin;

-    medicines used to treat fungal infections such as fluconazole, itraconazole and ketoconazole;

-    cimetidine, used to treat stomach ulcers;

-    naloxone used to reverse the effect of opioid drugs;

-    medicines used to stop opioid drugs working such as naltrexone and buprenorphine;

-    rifampicin, used to treat tuberculosis (TB);

-    medicines used to treat epilepsy such as phenytoin, carbamazepine, phenobarbital and primidone;

-    medicines that make your urine acidic, such as ascorbic acid (vitamin C) and ammonium chloride;

-    medicine used to treat diarrhoea (e.g. loperamide, diphenoxylate);

-    diuretic medicine (e.g. spironolactone);

-    medicine that makes you feel sleepy;

-    St. John's Wort-a herbal preparation for depression.

Other medicines you may be taking can also affect the heart (e.g sotalol, amiodarone and flecainide).

You must tell your doctor about any other medicine that you are taking as they may be dangerous if they are taken with methadone. In these situations your doctor may decide that it is necessary to monitor your heart with an electrocardiogram (ECG) at the start of treatment to ensure that these effects do not occur. Methadone may also affect some blood and urine tests (including doping tests). Please tell your doctor if you are taking methadone before any test is performed.

Misyo with food and drink and alcohol

Misyo can be taken with or without food.

Do not drink alcohol whilst taking Misyo. This is because methadone can make you feel sleepy and drinking alcohol will make you even sleepier.

Do not drink grapefruit juice whilst taking Misyo. This is because grapefruit juice may alter the effect of methadone.

Pregnancy, breast-feeding and fertility

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking this medicine. Take care if you are taking a pregnancy test as the Misyo may interfere with the results.

You should not take this medicine whilst you are in labour.

Driving and using machines

Methadone may severely affect your ability to drive or use machines, whilst taking it and afterwards. You should only start doing these activities again with the permission of your doctor.

The medicine can affect your ability to drive as it may make you sleepy or dizzy.

•    Do not drive while taking this medicine until you know how it affects you.

•    It is an offence to drive if this medicine affects your ability to drive.

•    However, you would not be committing an offence if:

-    The medicine has been prescribed to treat a medical or dental problem and

-    You have taken it according to the instructions given by the prescriber or in the information provided with the medicine and

-    It was not affecting your ability to drive safely

Details regarding a new driving offence concerning driving after drugs have been taken in the UK may be found here: https://www.gov.uk/drug-driving-law Talk to your doctor or pharmacist if you are not sure whether it is safe for you to drive while taking this medicine.

Misyo contains sorbitol

Misyo 10 mg/ml concentrate for oral solution contains sorbitol. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.

In some individuals sorbitol can affect how much methadone is absorbed from the swallowed dose. In these individuals, switching between Misyo 10 mg/ml concentrate for oral solution and other methadone products, which do not contain sorbitol, can cause change in methadone blood levels and return of symptoms. If this happens, please contact your doctor.

3. How to take Misyo

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

You must only take Misyo by mouth. Under no circumstances should you inject this product as injection as it may cause serious and permanent damage to your body with the possibility of fatal consequences. This product is intended to be diluted by a healthcare professional. You will receive Misyo in a diluted form.

Your doctor will tell you how much Misyo you need to take, and how often you need to take it. It is important that you do not take more than the dose agreed with your doctor.

Adults

The usual starting dose is 10-30 mg a day. The dose will be slowly increased until you show no signs of withdrawal or intoxication. The usual dose is 60-120 mg/day. Your doctor will decide what dose you need and when to reduce the dose.

Older people and very ill people

If you have to have repeated doses of this medicine, the doctor may want to monitor you more closely. If you are older, ill or have liver or kidney problems caution must be exercised and the dosage should be decreased.

Use in children

Misyo is not suitable for children.

If you take more Misyo than you should

If you take too much methadone you can experience the following:

-    difficulty breathing;

-    extreme sleepiness, fainting or coma;

-    pinpoint pupils;

-    muscle weakness;

-    cold and clammy skin;

-    slow heartbeat, low blood pressure, heart attack or shock;

-    in severe cases death may occur.

In the event of overdose you should seek medical assistance immediately even if you feel well as you may be suffering from methadone poisoning.

If you forget to take Misyo

If you forget a dose do not take it. Wait until the next dose is due and take only that amount. Do not take a double dose to make up for a forgotten dose.

If you stop taking Misyo

Do not stop taking this medicine unless your doctor tells you to as you may suffer withdrawal effects. Your doctor will tell you how to lower 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, this medicine can have undesirable effects, although not everybody gets them.

Stop taking this medicine and see a doctor straight away if you have any of the following:

-    Allergic reaction which may include: swelling of your face, lips, tongue or throat or difficulty breathing or swallowing or severe itching of your skin with raised lumps.

-    Heart problems. The signs of this may include changes in the way your heart beats, such as it beating faster or missed heart beats, breathing difficulties and dizziness if your breathing becomes slow and shallow. These side effects are rare and may affect up to 1 in 1,000 people.

-    If your breathing becomes slow and shallow.

-    Worsening of the pressure inside your head if you already have this condition following an injury to your brain or brain disease.

Keep taking the medicine but tell your doctor straight away if you get any of the following side effects:

-    if you have asthma and it gets worse.

Other possible side effects include:

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

-    feeling or being sick.

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

-    water retention;

-    feeling high (euphoria), seeing or hearing things that are not real (hallucinations);

-    feeling sleepy;

-    blurred vision, pin point pupils, dry eyes;

-    feeling of dizziness or spinning;

-    constipation;

-    skin rash, sweating;

-    feeling tired;

-    weight increase.

Uncommon (may affect up to 1 in 100 people):

-    feeling down (dysphoria), agitation, confusion, difficulty sleeping; reduction of sex drive;

-    headache, fainting;

-    low blood pressure, facial flush;

-    breathing difficulty (including with cough), dry nose;

-    dry mouth, inflammation of the tongue;

-    bile duct spasm (abdominal pain);

-    itching, hives, rash;

-    urine retention, difficulty in passing urine;

-    difficulty achieving or maintaining an erection;

-    disturbances of menstruation, production of breast milk;

-    swelling of the legs;

-    weakness;

-    low body temperature.

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

-    heart problems, slower heart beat, feeling your heart beat (palpitations);

-    shock;

-    respiratory arrest;

-    intestinal hypomotility (ileus).

The following side effects have also been reported:

-    lower levels of platelets in blood, which increases the risk of bleeding or bruising;

-    increased prolactin levels;

-    loss of appetite;

-    blood potassium or magnesium deficiency;

-    hearing loss.

Blood potassium or magnesium deficiency, hearing loss or lower levels of platelets in blood may also occur, although the frequency of these side effects is not known. Tell your doctor or pharmacist if any of the side effects get serious. Also tell them if you notice any side effects not listed in this leaflet. You can also report side effects directly via Yellow Card Scheme.

Website: 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 Misyo

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

Store below 25°C in the original package to protect from light.

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

After first opening store below 25°C in the original package to protect from light for not more than 90 days. Use within 90 days of opening.

Once diluted to concentration of 1 mg/ml or 5 mg/ml it has a 14 days shelf-life when stored in PET bottles below 25°C protected from light. Use within 14 days from diluting.

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

6. Contents of the pack and other information

What Misyo contains

-    The active substance is methadone.

Each 1 ml of the concentrate for oral solution contains 10 mg of methadone hydrochloride.

-    The other ingredients are: sorbitol, liquid non-crystallising (E420); glycerol (E422); sodium benzoate (E211); citric acid monohydrate (E330), colour brilliant blue FCF (E133) and water, purified.

What Misyo looks like and contents of the pack

Misyo is a clear blue solution.

100 ml pack size:

Carton box with a glass bottle containing 100 ml concentrate for oral solution with plastic cap or child-resistant plastic cap and a leaflet inside.

1000 ml pack size:

Carton box with a bottle containing 1000 ml concentrate for oral solution with plastic cap or child-resistant plastic cap and a leaflet inside.

Not all pack sizes may be marketed.

Marketing Authorisation Holder

INN-FARM d.o.o., Maleseva ulica 014, 1000 Ljubljana, Slovenia tel.: +386 70 390 711; fax: +386 5191 116; e-mail: info@innfarm.si Manufacturer

ALKALOID-INT d.o.o., Slandrova ulica 4, 1231 Ljubljana - Crnuce, Slovenia tel.: +386 1 300 42 90; fax: +386 1 300 42 91; e-mail: info@alkaloid.si

This medicinal product is authorised in the Member States of the EEA under the following names:

MISYO 10 mg/ml Concentrate for oral solution

MISYO 10 mg/ml Konzentrat zur Herstellung einer Losung zum Einnehmen

MISYO 10 mg/ml

MISYO 10 mg/ml Konzentrat zur Herstellung einer Losung zum Einnehmen

MISYO 10 mg/ml koncentratum belsoleges oldathoz MISYO 10 mg/ml concentrato per soluzione orale MISYO

MISYO 10 mg/ml Concentrado para solugao oral MISYO 10 mg/ml Concentrat pentru solujie orala MISYO 10 mg/ml

MISYO 10 mg/ml Concentrado para solucion oral

PL 40168/0001

This leaflet was last revised in 12/2015.

Misyo_oral solution_UK_mock_up_cor.2.indd 2 18-Dec-15 8:30:30 AM