Patient leaflet - Misyo 10 mg / ml concentrate for oral solution
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 to methadone, benzoates 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;
- if 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;
- if you are addicted to alcohol;
- if 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”)
- if you are not dependent on opioid drugs;
- if you have heart problems (QT prolongation);
- if you have severe liver problems;
- if 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 or asthma;
- 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 during treatment you notice that your breathing becomes slow and shallow, stop taking this medicine and see a doctor straight away. These may be signs of respiratory depression (see section 4) and may not be fully apparent for a week or two.
Talk to your doctor or pharmacist if you experience any of the following symptoms while taking Misyo: weakness, fatigue, lack of appetite, nausea, vomiting or low blood pressure. This may be a symptom of the adrenals producing too little of the hormone cortisol, and you may need to take hormone supplement.
Contact your doctor if you experience severe upper abdominal pain possibly radiating to the back, nausea, vomiting or fever as this could be symptoms associated with inflammation of the pancreas (pancreatitis) or the biliary tract system.
Long-term use may cause decreased sex hormone levels and increased levels of the hormone prolactin. Contact your doctor if you experience symptoms such as decreased libido, impotence or absence of menstruation (amenorrhea).
Sleep-related breathing disorders
Misyo can cause sleep-related breathing disorders such as sleep apnoea (breathing pauses during sleep) and sleep related hypoxemia (low oxygen level in the blood). The symptoms can include breathing pauses during sleep, night awakening due to shortness of breath, difficulties to maintain sleep or excessive drowsiness during the day. If you or another person observe these symptoms, contact your doctor. A dose reduction may be considered by your doctor.
Tolerance, dependence, and addiction
This medicine contains methadone which is an opioid medicine. Repeated use of opioids can result in the drug being less effective (you become accustomed to it, known as tolerance). Repeated use of Misyo can also lead to dependence, abuse, and addiction, which may result in life-threatening overdose.
Dependence or addiction can make you feel that you are no longer in control of how much medicine you need to take or how often you need to take it.
The risk of becoming dependent or addicted varies from person to person. You may have a greater risk of becoming dependent or addicted on Misyo if:
- You or anyone in your family have ever abused or been dependent on alcohol, prescription medicines or illegal drugs (“addiction”).
- You are a smoker.
- You have ever had problems with your mood (depression, anxiety, or a personality disorder) or have been treated by a psychiatrist for other mental illnesses.
If you notice any of the following signs whilst taking Misyo, it could be a sign that you have become dependent or addicted.
- You need to take the medicine for longer than advised by your doctor
- You need to take more than the recommended dose
- You are using the medicine for reasons other than prescribed, for instance, ‘to stay calm’ or ‘help you sleep’
- You have made repeated, unsuccessful attempts to quit or control the use of the medicine
When you stop taking the medicine you feel unwell, and you feel better once taking the medicine again (‘withdrawal effects’)
If you notice any of these signs, speak to your doctor to discuss the best treatment pathway for you, including when it is appropriate to stop and how to stop safely (See section 3, If you stop taking Misyo).
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. dexa-methasone 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;
- cannabidiol (a medicine used to treat seizures);
- gabapentin and pregabalin (medicines used to treat epilepsy, nerve pain or anxiety), can increase the risk of opioid overdose, respiratory depression (breathing difficulties) and may be life-threatening;
- medicines that make your urine acidic, such as ascorbic acid (vitamin C) and ammonium chloride;
- medicine used to treat diarrhoea (e.g. loperamide, dipheno xylate);
- diuretic medicine (e.g. spironolactone);
- medicine that makes you feel sleepy;
- metamizole, a medicine used to treat pain and fever;
- St. John’s Wort-a herbal preparation for depression.
Concomitant use of Misyo and sedative medicines such as benzodiazepines or related drugs increases the risk of drowsiness, difficulties in breathing (respiratory depression), coma and may be life-threatening. Because of this, concomitant use should only be considered when other treatment options are not possible.
However if your doctor does prescribe Misyo together with sedative medicines the dose and duration of concomitant treatment should be limited by your doctor.
Please tell your doctor about all sedative medicines you are taking, and follow your doctor’s dose recommendation closely. It could be helpful to inform friends or relatives to be aware of the signs and symptoms stated above. Contact your doctor when experiencing such symptoms.
The risk of side effects increases, if you use methadone concomitantly with antidepressants (such as citalopram, duloxetine, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, venlafaxine, amitriptyline, clomipra-mine, imipramine, nortriptyline). Contact your doctor if you experience symptoms such as:
- mental-status changes (e.g. agitation, hallucinations, coma)
- fast heartbeat, unstable blood pressure, fever
- exaggeration of reflexes, impaired coordination, muscle stiffness
- gastrointestinal symptoms (e.g. nausea, vomiting, diarrhoea).
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, 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.
Pregnancy
Misyo may be used during pregnancy after careful risk-benefit assessment by a doctor, preferably under supervision in a specialised medical centre. Dose increase up to twice a day may be necessary to maintain the effectiveness of the treatment due to changes in metabolism during the course of pregnancy.
Chronic use during pregnancy may lead to methadone habituation and addiction of the foetus as well as to withdrawal symptoms after birth which often requires hospitalised treatment.
Some studies have reported birth defects or neurodevelopmental problems (problems with early childhood development) in children born to mothers who used methadone during pregnancy to treat opioid addiction. However, it is not possible to determine if this is caused by methadone use or other factors such as the health of the mother and social and environmental conditions associated with opioid addiction.
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.
Breast-feeding
Talk to your doctor if you are breastfeeding or thinking of breast-feeding while you are taking methadone as it may affect your baby. Monitor your baby for abnormal signs and symptoms such as increased drowsiness (more than usual), breathing difficulties or limpness. Consult your doctor immediately if you notice any of these symptoms.
Fertility
Methadone has been reported to cause sexual dysfunction in male patients on maintenance treatment.
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
Package leaflet: Information for the user
MISYO
10 mg/ml concentrate for oral solution
Methadone hydrochloride
- 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
This medicine contains 300 mg sorbitol, liquid non-crystallising (which is equivalent to 210 mg of sorbitol) in each 1 ml.
Sorbitol is a source of fructose. If your doctor has told you that you have an intolerance to some sugars or if you have been diagnosed with hereditary fructose intolerance (HFI), a rare genetic disorder in which a person cannot break down fructose, talk to your doctor before you take or receive this medicine.
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.
Misyo contains sodium benzoate
This medicine contains 3 mg sodium benzoate in each 1 ml. Although this medicine is not intended for use in newborns, it is important to know that sodium benzoate may increase jaundice (yellowing of the skin and eyes) in newborn babies (up to 4 weeks old).
This medicine contains less than 1 mmol sodium (23 mg) per ml, that is to say essentially ‘sodium-free’.
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;
- low blood sugar;
- slow heartbeat, low blood pressure, heart attack or shock;
- a brain disorder (known as toxic leukoencephalopathy);
- 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 (frequency not known):
- 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;
- Low blood sugar;
- Eye and eyesight problems in babies and young children born to mothers who used methadone during pregnancy. This may mean your child needs more frequent eye-tests.
- Hearing loss;
- You can become dependent on Misyo (for more information see section 2 Warnings and Precautions);
- Sleep apnoea (breathing pauses during sleep);
- Symptoms associated with inflammation of the pancreas (pancreatitis) and the biliary tract system (a problem affecting a valve in the intestines known as sphincter of Oddi dysfunction), e.g. severe upper abdominal pain possibly radiating to the back, nausea, vomiting or fever.
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.
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 Yellow Card Scheme
Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. 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 this medicine in a safe and secure storage space, where other people cannot access it. It can cause serious harm and be fatal to people when it has not been prescribed for them.
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.
Store below 25ºC in the original package to protect from light.
After first opening store below 25ºC 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 25ºC 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 (E 133) 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., Maleševa 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., Šlandrova ulica 4, 1231 Ljubljana – Črnuče, Slovenia
tel.: 386 1 300 42 90
fax: 386 1 300 42 91
e-mail: info@alkaloid.si
PL 40168/0001